MDedge Psychiatry

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

A version of this article first appeared on Medscape.com.

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

A version of this article first appeared on Medscape.com.

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

A version of this article first appeared on Medscape.com.

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

A version of this article originally appeared on Medscape.com.

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

A version of this article originally appeared on Medscape.com.

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

A version of this article originally appeared on Medscape.com.

Major depressive disorder (MDD) is linked to disruptions in energy and lipid metabolism, possibly caused by the interplay of the gut microbiome and blood metabolome, new research suggests.

Investigators found that MDD had specific metabolic “signatures” consisting of 124 metabolites that spanned energy and lipid pathways, with some involving the tricarboxylic acid cycle in particular. These changes in metabolites were consistent with differences in composition of several gut microbiota.

The researchers found that fatty acids and intermediate and very large lipoproteins changed in association with the depressive disease process. However, high-density lipoproteins and metabolites in the tricarboxylic acid cycle did not.

“As we wait to establish causal influences through clinical trials, clinicians should advise patients suffering from mood disorders to modify their diet by increasing the intake of fresh fruits, vegetables, and whole grains, as these provide the required fuel/fiber to the gut microbiota for their enrichment, and more short-chain fatty acids are produced for the optimal functioning of the body,” study investigator Najaf Amin, PhD, DSc, senior researcher, Nuffield Department of Population Health, Oxford University, England, told this news organization.

“At the same time, patients should be advised to minimize the intake of sugars and processed foods, which are known to have an inverse impact on the gut microbiome and are associated with higher inflammation,” she said.

The study was published online in JAMA Psychiatry.
 

MDD poorly understood

Although most antidepressants target the monoamine pathway, “evidence is increasing for a more complex interplay of multiple pathways involving a wide range of metabolic alterations spanning energy and lipid metabolism,” the authors wrote.

Previous research using the Nightingale proton nuclear magnetic resonance (NMR) metabolomics platform showed a “shift” toward decreased levels of high-density lipoproteins (HDLs) and increased levels of very low-density lipoproteins (VLDLs) and triglycerides among patients with depression.

The gut microbiome, which is primarily modulated by diet, “has been shown to be a major determinant of circulating lipids, specifically triglycerides and HDLs, and to regulate mitochondrial function,” the investigators noted. Patients with MDD are known to have disruptions in the gut microbiome.

The gut microbiome may “explain part of the shift in VLDL and HDL levels observed in patients with depression and if the metabolic signatures of the disease based on Nightingale metabolites can be used as a tool to infer the association between gut microbiome and depression.”

Dr. Amin called depression “one of the most poorly understood diseases, as underlying mechanisms remain elusive.”

Large-scale genetic studies “have shown that the contribution of genetics to depression is modest,” she continued. On the other hand, initial animal studies suggest the gut microbiome “may potentially have a causal influence on depression.”

Several studies have evaluated the influence of gut microbiome on depression, “but, due to small sample sizes and inadequate control for confounding factors, most of their findings were not reproducible.”

Harnessing the power of the UK Biobank, the investigators studied 58,257 individuals who were between the ages of 37 and 73 years at recruitment. They used data on NMR spectroscopy–based plasma metabolites in depression. Individuals who didn’t report depression at baseline served as controls.

Logistic regression analysis was used to test the association of metabolite levels with depression in four models, each with an increasing number of covariates.

To identify patterns of correlation in the “metabolic signatures of MDD and the human gut biome,” they regressed the metabolic signatures of MDD on the metabolic signatures of the gut microbiota and then regressed the metabolic signature of gut microbiota on the metabolic signatures of MDD.

Bidirectional 2-sample Mendelian randomization was used to ascertain the direction of the association observed between metabolites and MDD.

Individuals with lifetime and recurrent MDD were compared with controls (6,811 vs. 51,446 and 4,370 vs. 62,508, respectively).

Participants with lifetime MDD were significantly younger (median [IQR] age, 56 [49-62] years vs. 58 [51-64] years) and were more likely to be female in comparison with controls (54% vs. 35%).
 

‘Novel findings’

In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.

The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.

The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.

“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”

These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.

Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
 

No causality

Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”

However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.

Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.

Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
 

A version of this article originally appeared on Medscape.com.

Major depressive disorder (MDD) is linked to disruptions in energy and lipid metabolism, possibly caused by the interplay of the gut microbiome and blood metabolome, new research suggests.

Investigators found that MDD had specific metabolic “signatures” consisting of 124 metabolites that spanned energy and lipid pathways, with some involving the tricarboxylic acid cycle in particular. These changes in metabolites were consistent with differences in composition of several gut microbiota.

The researchers found that fatty acids and intermediate and very large lipoproteins changed in association with the depressive disease process. However, high-density lipoproteins and metabolites in the tricarboxylic acid cycle did not.

“As we wait to establish causal influences through clinical trials, clinicians should advise patients suffering from mood disorders to modify their diet by increasing the intake of fresh fruits, vegetables, and whole grains, as these provide the required fuel/fiber to the gut microbiota for their enrichment, and more short-chain fatty acids are produced for the optimal functioning of the body,” study investigator Najaf Amin, PhD, DSc, senior researcher, Nuffield Department of Population Health, Oxford University, England, told this news organization.

“At the same time, patients should be advised to minimize the intake of sugars and processed foods, which are known to have an inverse impact on the gut microbiome and are associated with higher inflammation,” she said.

The study was published online in JAMA Psychiatry.
 

MDD poorly understood

Although most antidepressants target the monoamine pathway, “evidence is increasing for a more complex interplay of multiple pathways involving a wide range of metabolic alterations spanning energy and lipid metabolism,” the authors wrote.

Previous research using the Nightingale proton nuclear magnetic resonance (NMR) metabolomics platform showed a “shift” toward decreased levels of high-density lipoproteins (HDLs) and increased levels of very low-density lipoproteins (VLDLs) and triglycerides among patients with depression.

The gut microbiome, which is primarily modulated by diet, “has been shown to be a major determinant of circulating lipids, specifically triglycerides and HDLs, and to regulate mitochondrial function,” the investigators noted. Patients with MDD are known to have disruptions in the gut microbiome.

The gut microbiome may “explain part of the shift in VLDL and HDL levels observed in patients with depression and if the metabolic signatures of the disease based on Nightingale metabolites can be used as a tool to infer the association between gut microbiome and depression.”

Dr. Amin called depression “one of the most poorly understood diseases, as underlying mechanisms remain elusive.”

Large-scale genetic studies “have shown that the contribution of genetics to depression is modest,” she continued. On the other hand, initial animal studies suggest the gut microbiome “may potentially have a causal influence on depression.”

Several studies have evaluated the influence of gut microbiome on depression, “but, due to small sample sizes and inadequate control for confounding factors, most of their findings were not reproducible.”

Harnessing the power of the UK Biobank, the investigators studied 58,257 individuals who were between the ages of 37 and 73 years at recruitment. They used data on NMR spectroscopy–based plasma metabolites in depression. Individuals who didn’t report depression at baseline served as controls.

Logistic regression analysis was used to test the association of metabolite levels with depression in four models, each with an increasing number of covariates.

To identify patterns of correlation in the “metabolic signatures of MDD and the human gut biome,” they regressed the metabolic signatures of MDD on the metabolic signatures of the gut microbiota and then regressed the metabolic signature of gut microbiota on the metabolic signatures of MDD.

Bidirectional 2-sample Mendelian randomization was used to ascertain the direction of the association observed between metabolites and MDD.

Individuals with lifetime and recurrent MDD were compared with controls (6,811 vs. 51,446 and 4,370 vs. 62,508, respectively).

Participants with lifetime MDD were significantly younger (median [IQR] age, 56 [49-62] years vs. 58 [51-64] years) and were more likely to be female in comparison with controls (54% vs. 35%).
 

‘Novel findings’

In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.

The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.

The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.

“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”

These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.

Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
 

No causality

Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”

However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.

Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.

Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
 

A version of this article originally appeared on Medscape.com.

Major depressive disorder (MDD) is linked to disruptions in energy and lipid metabolism, possibly caused by the interplay of the gut microbiome and blood metabolome, new research suggests.

Investigators found that MDD had specific metabolic “signatures” consisting of 124 metabolites that spanned energy and lipid pathways, with some involving the tricarboxylic acid cycle in particular. These changes in metabolites were consistent with differences in composition of several gut microbiota.

The researchers found that fatty acids and intermediate and very large lipoproteins changed in association with the depressive disease process. However, high-density lipoproteins and metabolites in the tricarboxylic acid cycle did not.

“As we wait to establish causal influences through clinical trials, clinicians should advise patients suffering from mood disorders to modify their diet by increasing the intake of fresh fruits, vegetables, and whole grains, as these provide the required fuel/fiber to the gut microbiota for their enrichment, and more short-chain fatty acids are produced for the optimal functioning of the body,” study investigator Najaf Amin, PhD, DSc, senior researcher, Nuffield Department of Population Health, Oxford University, England, told this news organization.

“At the same time, patients should be advised to minimize the intake of sugars and processed foods, which are known to have an inverse impact on the gut microbiome and are associated with higher inflammation,” she said.

The study was published online in JAMA Psychiatry.
 

MDD poorly understood

Although most antidepressants target the monoamine pathway, “evidence is increasing for a more complex interplay of multiple pathways involving a wide range of metabolic alterations spanning energy and lipid metabolism,” the authors wrote.

Previous research using the Nightingale proton nuclear magnetic resonance (NMR) metabolomics platform showed a “shift” toward decreased levels of high-density lipoproteins (HDLs) and increased levels of very low-density lipoproteins (VLDLs) and triglycerides among patients with depression.

The gut microbiome, which is primarily modulated by diet, “has been shown to be a major determinant of circulating lipids, specifically triglycerides and HDLs, and to regulate mitochondrial function,” the investigators noted. Patients with MDD are known to have disruptions in the gut microbiome.

The gut microbiome may “explain part of the shift in VLDL and HDL levels observed in patients with depression and if the metabolic signatures of the disease based on Nightingale metabolites can be used as a tool to infer the association between gut microbiome and depression.”

Dr. Amin called depression “one of the most poorly understood diseases, as underlying mechanisms remain elusive.”

Large-scale genetic studies “have shown that the contribution of genetics to depression is modest,” she continued. On the other hand, initial animal studies suggest the gut microbiome “may potentially have a causal influence on depression.”

Several studies have evaluated the influence of gut microbiome on depression, “but, due to small sample sizes and inadequate control for confounding factors, most of their findings were not reproducible.”

Harnessing the power of the UK Biobank, the investigators studied 58,257 individuals who were between the ages of 37 and 73 years at recruitment. They used data on NMR spectroscopy–based plasma metabolites in depression. Individuals who didn’t report depression at baseline served as controls.

Logistic regression analysis was used to test the association of metabolite levels with depression in four models, each with an increasing number of covariates.

To identify patterns of correlation in the “metabolic signatures of MDD and the human gut biome,” they regressed the metabolic signatures of MDD on the metabolic signatures of the gut microbiota and then regressed the metabolic signature of gut microbiota on the metabolic signatures of MDD.

Bidirectional 2-sample Mendelian randomization was used to ascertain the direction of the association observed between metabolites and MDD.

Individuals with lifetime and recurrent MDD were compared with controls (6,811 vs. 51,446 and 4,370 vs. 62,508, respectively).

Participants with lifetime MDD were significantly younger (median [IQR] age, 56 [49-62] years vs. 58 [51-64] years) and were more likely to be female in comparison with controls (54% vs. 35%).
 

‘Novel findings’

In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.

The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.

The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.

“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”

These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.

Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
 

No causality

Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”

However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.

Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.

Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
 

A version of this article originally appeared on Medscape.com.

Walnuts have been associated with better cognitive development and psychological maturation in teens, new research shows. Adolescents who consumed walnuts for at least 100 days showed improved sustained attention and fluid intelligence as well as a reduction in symptoms of attension deficit hyperactivity disorder, compared with matched controls who did not consume the nuts. However, there were no statistically significant changes between the groups in other parameters, such as working memory and executive function.

Clinicians should advise adolescents “to eat a handful of walnuts three times a week for the rest of their lives. They may have a healthier brain with better cognitive function,” said senior investigator Jordi Julvez, PhD, group leader at the Institute of Health Research Pere Virgili, Barcelona, and associated researcher at the Barcelona Institute for Global Health.

The study was published online in eClinicalMedicine.
 

Rich source of omega-3s

Adolescence is “a period of refinement of brain connectivity and complex behaviors,” the investigators noted.  

Previous research suggests polyunsaturated fatty acids are key in central nervous system architecture and function during times of neural development, with three specific PUFAs playing an “essential developmental role.”

Two omega-3 fatty acids – docosahexaenoic acid and eicosapentaenoic acid – are PUFAs that must be obtained through diet, mainly from seafood. Walnuts are “among the richest sources” of plant-derived omega-3 fatty acids, particularly alpha-linolenic acid (ALA), a precursor for longer-chain EPA and DHA.

ALA independently “has positive effects on brain function and plasticity,” the authors wrote. In addition, walnut constituents – particularly polyphenols and other bioactive compounds – “may act synergistically with ALA to foster brain health.”

Earlier small studies have found positive associations between walnut consumption and cognitive function in children, adolescents, and young adults, but to date, no randomized controlled trial has focused on the effect of walnut consumption on adolescent neuropsychological function.

The researchers studied 771 healthy adolescents (aged 11-16 years, mean age 14) drawn from 12 Spanish high schools. Participants were instructed to follow healthy eating recommendations and were randomly assigned 1:1 to the intervention (n = 386) or the control group (n = 385).

At baseline and after 6 months, they completed neuropsychological tests and behavioral rating scales. The Attention Network Test assessed attention, and the N-back test was used to assess working memory. The Tests of Primary Mental Abilities assessed fluid intelligence. Risky decision-making was tested using the Roulettes Task.
 

Fruit and nuts

Participants also completed the Strengths and Difficulties Questionnaire, which provided a total score of problem behavior. Teachers filled out the ADHD DSM-IV form list to provide additional information about ADHD behaviors.

The intervention group received 30 grams/day of raw California walnut kernels to incorporate into their daily diet. It is estimated that this walnut contains about 9 g of ALA per 100 g.

All participants received a seasonal fruit calendar and were asked to eat at least one piece of seasonal fruit daily.

Parents reported their child’s daily walnut consumption, with adherence defined as 100 or more days of eating walnuts during the 6-month period.

All main analyses were based on an intention-to-treat method (participants were analyzed according to their original group assignment, regardless of their adherence to the intervention).

The researchers also conducted a secondary per-protocol analysis, comparing the intervention and control groups to estimate the effect if all participants had adhered to their assigned intervention. They censored data for participants who reported eating walnuts for less than 100 days during the 6-month trial period.

Secondary outcomes included changes in height, weight, waist circumference, and BMI, as well as red blood cell proportions of omega-3 fatty acids (DHA, EPA, and ALA) at baseline and after 6 months.
 

Adherence counts

Most participants had “medium” or “high” levels of adherence to the Mediterranean diet, with “no meaningful differences” at baseline between the intervention and control groups in lifestyle characteristics or mean scores in all primary endpoints.

In the ITT analysis, there were no statistically significant differences in primary outcomes between the groups following the intervention. As for secondary outcomes, the RBC ALA significantly increased in the walnuts group but not the control group (coefficient, 0.04%; 95% confidence interval, 0.03%-0.06%; P < .0001).

However, there were differences in primary outcomes between the groups in the per-protocol analysis: The adherence-adjusted effect on improvement in attention score was −11.26 ms; 95% CI, −19.92 to −2.60; P = .011) for the intervention versus the control group.

The per-protocol analysis showed other differences: an improvement in fluid intelligence score (1.78; 95% CI, 0.90 - 2.67; P < .0001) and a reduction in ADHD symptom score (−2.18; 95% CI, −3.70 to −0.67; P = .0050).

“Overall, no significant differences were found in the intervention group in relation to the control group,” Dr. Julvez said in a news release. “But if the adherence factor is considered, then positive results are observed, since participants who most closely followed the guidelines – in terms of the recommended dose of walnuts and the number of days of consumption – did show improvements in the neuropsychological functions evaluated.”

Adolescence “is a time of great biological changes. Hormonal transformation occurs, which in turn is responsible for stimulating the synaptic growth of the frontal lobe,” he continued, adding that this brain region “enables neuropsychological maturation of more complex emotional and cognitive functions.”

“Neurons that are well nourished with these types of fatty acids will be able to grow and form new, stronger synapses,” he said.
 

Food as medicine

Uma Naidoo, MD, director of nutritional and lifestyle psychiatry at Massachusetts General Hospital, Boston, “commends” the researchers for conducting an RCT with a “robust” sample size and said she is “excited to see research like this furthering functional nutrition for mental health,” as she believes that “food is medicine.”

Dr. Naidoo, a professional chef, nutritional biologist, and author of the book “This Is Your Brain on Food,” said the findings “align” with her own approach to nutritional psychiatry and are also “in line” with her clinical practice.

However, although these results are “promising,” more research is needed across more diverse populations to “make sure these results are truly generalizable,” said Dr. Naidoo, a faculty member at Harvard Medical School, Boston, who was not involved with the study.

She “envisions a future where the research is so advanced that we can ‘dose’ these healthy whole foods for specific psychiatric symptoms and conditions.”

This study was supported by Instituto de Salud Carlos III (co-funded by European Union Regional Development Fund “A way to make Europe”). The California Walnut Commission has given support by supplying the walnuts for free for the Walnuts Smart Snack Dietary Intervention Trial. Dr. Julvez holds a Miguel Servet-II contract awarded by the Instituto de Salud Carlos III (co-funded by European Union Social Fund). The other authors’ disclosures are listed in the original article. Dr. Naidoo reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Walnuts have been associated with better cognitive development and psychological maturation in teens, new research shows. Adolescents who consumed walnuts for at least 100 days showed improved sustained attention and fluid intelligence as well as a reduction in symptoms of attension deficit hyperactivity disorder, compared with matched controls who did not consume the nuts. However, there were no statistically significant changes between the groups in other parameters, such as working memory and executive function.

Clinicians should advise adolescents “to eat a handful of walnuts three times a week for the rest of their lives. They may have a healthier brain with better cognitive function,” said senior investigator Jordi Julvez, PhD, group leader at the Institute of Health Research Pere Virgili, Barcelona, and associated researcher at the Barcelona Institute for Global Health.

The study was published online in eClinicalMedicine.
 

Rich source of omega-3s

Adolescence is “a period of refinement of brain connectivity and complex behaviors,” the investigators noted.  

Previous research suggests polyunsaturated fatty acids are key in central nervous system architecture and function during times of neural development, with three specific PUFAs playing an “essential developmental role.”

Two omega-3 fatty acids – docosahexaenoic acid and eicosapentaenoic acid – are PUFAs that must be obtained through diet, mainly from seafood. Walnuts are “among the richest sources” of plant-derived omega-3 fatty acids, particularly alpha-linolenic acid (ALA), a precursor for longer-chain EPA and DHA.

ALA independently “has positive effects on brain function and plasticity,” the authors wrote. In addition, walnut constituents – particularly polyphenols and other bioactive compounds – “may act synergistically with ALA to foster brain health.”

Earlier small studies have found positive associations between walnut consumption and cognitive function in children, adolescents, and young adults, but to date, no randomized controlled trial has focused on the effect of walnut consumption on adolescent neuropsychological function.

The researchers studied 771 healthy adolescents (aged 11-16 years, mean age 14) drawn from 12 Spanish high schools. Participants were instructed to follow healthy eating recommendations and were randomly assigned 1:1 to the intervention (n = 386) or the control group (n = 385).

At baseline and after 6 months, they completed neuropsychological tests and behavioral rating scales. The Attention Network Test assessed attention, and the N-back test was used to assess working memory. The Tests of Primary Mental Abilities assessed fluid intelligence. Risky decision-making was tested using the Roulettes Task.
 

Fruit and nuts

Participants also completed the Strengths and Difficulties Questionnaire, which provided a total score of problem behavior. Teachers filled out the ADHD DSM-IV form list to provide additional information about ADHD behaviors.

The intervention group received 30 grams/day of raw California walnut kernels to incorporate into their daily diet. It is estimated that this walnut contains about 9 g of ALA per 100 g.

All participants received a seasonal fruit calendar and were asked to eat at least one piece of seasonal fruit daily.

Parents reported their child’s daily walnut consumption, with adherence defined as 100 or more days of eating walnuts during the 6-month period.

All main analyses were based on an intention-to-treat method (participants were analyzed according to their original group assignment, regardless of their adherence to the intervention).

The researchers also conducted a secondary per-protocol analysis, comparing the intervention and control groups to estimate the effect if all participants had adhered to their assigned intervention. They censored data for participants who reported eating walnuts for less than 100 days during the 6-month trial period.

Secondary outcomes included changes in height, weight, waist circumference, and BMI, as well as red blood cell proportions of omega-3 fatty acids (DHA, EPA, and ALA) at baseline and after 6 months.
 

Adherence counts

Most participants had “medium” or “high” levels of adherence to the Mediterranean diet, with “no meaningful differences” at baseline between the intervention and control groups in lifestyle characteristics or mean scores in all primary endpoints.

In the ITT analysis, there were no statistically significant differences in primary outcomes between the groups following the intervention. As for secondary outcomes, the RBC ALA significantly increased in the walnuts group but not the control group (coefficient, 0.04%; 95% confidence interval, 0.03%-0.06%; P < .0001).

However, there were differences in primary outcomes between the groups in the per-protocol analysis: The adherence-adjusted effect on improvement in attention score was −11.26 ms; 95% CI, −19.92 to −2.60; P = .011) for the intervention versus the control group.

The per-protocol analysis showed other differences: an improvement in fluid intelligence score (1.78; 95% CI, 0.90 - 2.67; P < .0001) and a reduction in ADHD symptom score (−2.18; 95% CI, −3.70 to −0.67; P = .0050).

“Overall, no significant differences were found in the intervention group in relation to the control group,” Dr. Julvez said in a news release. “But if the adherence factor is considered, then positive results are observed, since participants who most closely followed the guidelines – in terms of the recommended dose of walnuts and the number of days of consumption – did show improvements in the neuropsychological functions evaluated.”

Adolescence “is a time of great biological changes. Hormonal transformation occurs, which in turn is responsible for stimulating the synaptic growth of the frontal lobe,” he continued, adding that this brain region “enables neuropsychological maturation of more complex emotional and cognitive functions.”

“Neurons that are well nourished with these types of fatty acids will be able to grow and form new, stronger synapses,” he said.
 

Food as medicine

Uma Naidoo, MD, director of nutritional and lifestyle psychiatry at Massachusetts General Hospital, Boston, “commends” the researchers for conducting an RCT with a “robust” sample size and said she is “excited to see research like this furthering functional nutrition for mental health,” as she believes that “food is medicine.”

Dr. Naidoo, a professional chef, nutritional biologist, and author of the book “This Is Your Brain on Food,” said the findings “align” with her own approach to nutritional psychiatry and are also “in line” with her clinical practice.

However, although these results are “promising,” more research is needed across more diverse populations to “make sure these results are truly generalizable,” said Dr. Naidoo, a faculty member at Harvard Medical School, Boston, who was not involved with the study.

She “envisions a future where the research is so advanced that we can ‘dose’ these healthy whole foods for specific psychiatric symptoms and conditions.”

This study was supported by Instituto de Salud Carlos III (co-funded by European Union Regional Development Fund “A way to make Europe”). The California Walnut Commission has given support by supplying the walnuts for free for the Walnuts Smart Snack Dietary Intervention Trial. Dr. Julvez holds a Miguel Servet-II contract awarded by the Instituto de Salud Carlos III (co-funded by European Union Social Fund). The other authors’ disclosures are listed in the original article. Dr. Naidoo reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Walnuts have been associated with better cognitive development and psychological maturation in teens, new research shows. Adolescents who consumed walnuts for at least 100 days showed improved sustained attention and fluid intelligence as well as a reduction in symptoms of attension deficit hyperactivity disorder, compared with matched controls who did not consume the nuts. However, there were no statistically significant changes between the groups in other parameters, such as working memory and executive function.

Clinicians should advise adolescents “to eat a handful of walnuts three times a week for the rest of their lives. They may have a healthier brain with better cognitive function,” said senior investigator Jordi Julvez, PhD, group leader at the Institute of Health Research Pere Virgili, Barcelona, and associated researcher at the Barcelona Institute for Global Health.

The study was published online in eClinicalMedicine.
 

Rich source of omega-3s

Adolescence is “a period of refinement of brain connectivity and complex behaviors,” the investigators noted.  

Previous research suggests polyunsaturated fatty acids are key in central nervous system architecture and function during times of neural development, with three specific PUFAs playing an “essential developmental role.”

Two omega-3 fatty acids – docosahexaenoic acid and eicosapentaenoic acid – are PUFAs that must be obtained through diet, mainly from seafood. Walnuts are “among the richest sources” of plant-derived omega-3 fatty acids, particularly alpha-linolenic acid (ALA), a precursor for longer-chain EPA and DHA.

ALA independently “has positive effects on brain function and plasticity,” the authors wrote. In addition, walnut constituents – particularly polyphenols and other bioactive compounds – “may act synergistically with ALA to foster brain health.”

Earlier small studies have found positive associations between walnut consumption and cognitive function in children, adolescents, and young adults, but to date, no randomized controlled trial has focused on the effect of walnut consumption on adolescent neuropsychological function.

The researchers studied 771 healthy adolescents (aged 11-16 years, mean age 14) drawn from 12 Spanish high schools. Participants were instructed to follow healthy eating recommendations and were randomly assigned 1:1 to the intervention (n = 386) or the control group (n = 385).

At baseline and after 6 months, they completed neuropsychological tests and behavioral rating scales. The Attention Network Test assessed attention, and the N-back test was used to assess working memory. The Tests of Primary Mental Abilities assessed fluid intelligence. Risky decision-making was tested using the Roulettes Task.
 

Fruit and nuts

Participants also completed the Strengths and Difficulties Questionnaire, which provided a total score of problem behavior. Teachers filled out the ADHD DSM-IV form list to provide additional information about ADHD behaviors.

The intervention group received 30 grams/day of raw California walnut kernels to incorporate into their daily diet. It is estimated that this walnut contains about 9 g of ALA per 100 g.

All participants received a seasonal fruit calendar and were asked to eat at least one piece of seasonal fruit daily.

Parents reported their child’s daily walnut consumption, with adherence defined as 100 or more days of eating walnuts during the 6-month period.

All main analyses were based on an intention-to-treat method (participants were analyzed according to their original group assignment, regardless of their adherence to the intervention).

The researchers also conducted a secondary per-protocol analysis, comparing the intervention and control groups to estimate the effect if all participants had adhered to their assigned intervention. They censored data for participants who reported eating walnuts for less than 100 days during the 6-month trial period.

Secondary outcomes included changes in height, weight, waist circumference, and BMI, as well as red blood cell proportions of omega-3 fatty acids (DHA, EPA, and ALA) at baseline and after 6 months.
 

Adherence counts

Most participants had “medium” or “high” levels of adherence to the Mediterranean diet, with “no meaningful differences” at baseline between the intervention and control groups in lifestyle characteristics or mean scores in all primary endpoints.

In the ITT analysis, there were no statistically significant differences in primary outcomes between the groups following the intervention. As for secondary outcomes, the RBC ALA significantly increased in the walnuts group but not the control group (coefficient, 0.04%; 95% confidence interval, 0.03%-0.06%; P < .0001).

However, there were differences in primary outcomes between the groups in the per-protocol analysis: The adherence-adjusted effect on improvement in attention score was −11.26 ms; 95% CI, −19.92 to −2.60; P = .011) for the intervention versus the control group.

The per-protocol analysis showed other differences: an improvement in fluid intelligence score (1.78; 95% CI, 0.90 - 2.67; P < .0001) and a reduction in ADHD symptom score (−2.18; 95% CI, −3.70 to −0.67; P = .0050).

“Overall, no significant differences were found in the intervention group in relation to the control group,” Dr. Julvez said in a news release. “But if the adherence factor is considered, then positive results are observed, since participants who most closely followed the guidelines – in terms of the recommended dose of walnuts and the number of days of consumption – did show improvements in the neuropsychological functions evaluated.”

Adolescence “is a time of great biological changes. Hormonal transformation occurs, which in turn is responsible for stimulating the synaptic growth of the frontal lobe,” he continued, adding that this brain region “enables neuropsychological maturation of more complex emotional and cognitive functions.”

“Neurons that are well nourished with these types of fatty acids will be able to grow and form new, stronger synapses,” he said.
 

Food as medicine

Uma Naidoo, MD, director of nutritional and lifestyle psychiatry at Massachusetts General Hospital, Boston, “commends” the researchers for conducting an RCT with a “robust” sample size and said she is “excited to see research like this furthering functional nutrition for mental health,” as she believes that “food is medicine.”

Dr. Naidoo, a professional chef, nutritional biologist, and author of the book “This Is Your Brain on Food,” said the findings “align” with her own approach to nutritional psychiatry and are also “in line” with her clinical practice.

However, although these results are “promising,” more research is needed across more diverse populations to “make sure these results are truly generalizable,” said Dr. Naidoo, a faculty member at Harvard Medical School, Boston, who was not involved with the study.

She “envisions a future where the research is so advanced that we can ‘dose’ these healthy whole foods for specific psychiatric symptoms and conditions.”

This study was supported by Instituto de Salud Carlos III (co-funded by European Union Regional Development Fund “A way to make Europe”). The California Walnut Commission has given support by supplying the walnuts for free for the Walnuts Smart Snack Dietary Intervention Trial. Dr. Julvez holds a Miguel Servet-II contract awarded by the Instituto de Salud Carlos III (co-funded by European Union Social Fund). The other authors’ disclosures are listed in the original article. Dr. Naidoo reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

WASHINGTON – Psilocybin is safe and effective in patients with body dysmorphic disorder (BDD), preliminary findings of a small pilot study show.

“The results suggest that psilocybin appears to be relatively safe and potentially helpful for people with BDD, and that it has a broader scope than just depression,” study investigator Franklin Schneier, MD, codirector of the Anxiety Disorders Clinic, New York State Psychiatric Institute, and special lecturer in psychiatry at Columbia University Medical Center in New York City, told this news organization.

So far, psilocybin has mostly been examined in clinical trials among patients with major depression. Dr. Schneier said he is aware of only a single case in the literature of its use in BDD: a patient who self-treated with psilocybin and reported symptom improvement.

The current study was presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Few treatment options

Patients with BDD are preoccupied with a body part they perceive as ugly or defective, “and not just mildly so,” said Dr. Schneier. “It bothers them to the extreme such that they may obsess about it on and off all day long.”

Such patients may engage in compulsive behaviors like constantly checking themselves in the mirror, and going to great lengths to conceal the body part they feel is defective. “They often seek out cosmetic procedures that objectively aren’t warranted,” said Dr. Schneier.

BDD patients often have comorbid depression, and many attempt suicide. As with other anxiety and depressive disorders, BDD is twice as prevalent in women vs. men, said Dr. Schneier.

Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are the only approved therapies for BDD.

The investigators thought there may be a good chance BDD patients could benefit from psilocybin. Psilocybin alters bodily self-awareness, which “might shake up people’s beliefs about their abnormal body perceptions,” said Dr. Schneier.

There’s also some suggestion that psilocybin relaxes inflexible thinking, he added. “People with BDD have very rigid beliefs about their body distortions that aren’t easily swayed by logic.”

The study included 12 adults (8 women, 4 men) with a mean age of 34 years and moderate to severe BDD who failed at least one SSRI course and had had BDD for an average of 21 years.

Participants had preliminary sessions with a therapist familiar with psilocybin who prepared them psychologically and discussed what to expect from the experience. On the day of the intervention, subjects took a single 25 mg oral dose of synthetic psilocybin in a comfortable setting.

Therapists were present for the next 8 hours to answer questions and support subjects through the experience.
 

High response rate

The primary efficacy outcome was change in the BDD Yale-Brown Obsessive Compulsive Disorder Scale Modified (BDD-YBOCS) total score.

The mean baseline BDD-YBOCS score was 29.17. Researchers regularly assessed this score in the following weeks.

At 12 weeks, BDD-YBOCS scores decreased significantly from baseline (P < .001) with a large effect size (partial eta squared = .54).

However, said Dr. Schneier, what really stood out was the proportion of responders. At week 12, seven (58%) of the 12 participants were responders, as defined by a 30% or greater decrease in the BDD-YBOCS score. Of these, three were “almost symptom-free,” he added.

A number of secondary outcomes, including conviction of belief, disability, and negative affect, also significantly improved.

It’s too early to determine if additional treatment is required. The investigators plan to follow-up with the cohort at 1 year.

Although exciting, these early results warrant caution, said Dr. Schneier. “On the one hand, this is a sample of people who have struggled for a long time and have failed previous therapies, so that’s good. But on the other hand, it’s an open trial with no placebo group, and everyone has high expectations, so we don’t know how much of a placebo effect there was.”

Most adverse events, including headaches and fatigue, were mild and resolved within the first week after dosing, and there were no serious adverse events.

Based on these findings, Dr. Schneier said controlled trials of psilocybin in BDD are warranted.
 

Need for scientific rigor

Commenting on the research, Charles B. Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, University of Texas at Austin, said while promising, psilocybin is “not for everyone” and patients need to be closely screened.

University of Texas at Austin

“We want to know their medical history and if they have a family history of schizophrenia or bipolar disorder. We don’t know whether these [psychedelic] medicines might trigger an episode.”

Dr. Nemeroff also noted there’s a risk of “troubling” side effects from the drug.

“My view is psilocybin clearly has therapeutic effects and we need to apply scientific rigor as we would any medicine in order to determine the risk/benefit ratio,” said Dr. Nemeroff, who was not associated with this psilocybin trial.

In addition, psilocybin is being tested in conditions other than BDD and major depression, including anorexia nervosa, postpartum depression, and alcohol use disorder, he added.

The study received funding from COMPASS Pathways PLC.

Dr. Nemeroff reports he has received research support from the NIH and Stanley Medical Research Institute; served as a consultant for Bracket (Clintara), Fortress Biotech, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Sunovion Pharmaceuticals, Taisho Pharmaceuticals, Takeda, TC MSO, and Xhale; served on scientific advisory boards for the American Foundation for Suicide Prevention, the Anxiety and Depression Association of America, Bracket (Clintara), Brain and Behavior Research Foundation, Laureate Institute for Brain Research, Skyland Trail, and Xhale; is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, OPKO Health, Seattle Genetics, and Xhale; serves on the board of directors for the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, and Gratitude America; has received income or equity of $10,000 or more from American Psychiatric Publishing, Bracket (Clintara), Magstim, CME Outfitters, and Intra-Cellular Therapies; and holds patents on a method and devices for transdermal delivery of lithium and a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay.

A version of this article first appeared on Medscape.com.

WASHINGTON – Psilocybin is safe and effective in patients with body dysmorphic disorder (BDD), preliminary findings of a small pilot study show.

“The results suggest that psilocybin appears to be relatively safe and potentially helpful for people with BDD, and that it has a broader scope than just depression,” study investigator Franklin Schneier, MD, codirector of the Anxiety Disorders Clinic, New York State Psychiatric Institute, and special lecturer in psychiatry at Columbia University Medical Center in New York City, told this news organization.

So far, psilocybin has mostly been examined in clinical trials among patients with major depression. Dr. Schneier said he is aware of only a single case in the literature of its use in BDD: a patient who self-treated with psilocybin and reported symptom improvement.

The current study was presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Few treatment options

Patients with BDD are preoccupied with a body part they perceive as ugly or defective, “and not just mildly so,” said Dr. Schneier. “It bothers them to the extreme such that they may obsess about it on and off all day long.”

Such patients may engage in compulsive behaviors like constantly checking themselves in the mirror, and going to great lengths to conceal the body part they feel is defective. “They often seek out cosmetic procedures that objectively aren’t warranted,” said Dr. Schneier.

BDD patients often have comorbid depression, and many attempt suicide. As with other anxiety and depressive disorders, BDD is twice as prevalent in women vs. men, said Dr. Schneier.

Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are the only approved therapies for BDD.

The investigators thought there may be a good chance BDD patients could benefit from psilocybin. Psilocybin alters bodily self-awareness, which “might shake up people’s beliefs about their abnormal body perceptions,” said Dr. Schneier.

There’s also some suggestion that psilocybin relaxes inflexible thinking, he added. “People with BDD have very rigid beliefs about their body distortions that aren’t easily swayed by logic.”

The study included 12 adults (8 women, 4 men) with a mean age of 34 years and moderate to severe BDD who failed at least one SSRI course and had had BDD for an average of 21 years.

Participants had preliminary sessions with a therapist familiar with psilocybin who prepared them psychologically and discussed what to expect from the experience. On the day of the intervention, subjects took a single 25 mg oral dose of synthetic psilocybin in a comfortable setting.

Therapists were present for the next 8 hours to answer questions and support subjects through the experience.
 

High response rate

The primary efficacy outcome was change in the BDD Yale-Brown Obsessive Compulsive Disorder Scale Modified (BDD-YBOCS) total score.

The mean baseline BDD-YBOCS score was 29.17. Researchers regularly assessed this score in the following weeks.

At 12 weeks, BDD-YBOCS scores decreased significantly from baseline (P < .001) with a large effect size (partial eta squared = .54).

However, said Dr. Schneier, what really stood out was the proportion of responders. At week 12, seven (58%) of the 12 participants were responders, as defined by a 30% or greater decrease in the BDD-YBOCS score. Of these, three were “almost symptom-free,” he added.

A number of secondary outcomes, including conviction of belief, disability, and negative affect, also significantly improved.

It’s too early to determine if additional treatment is required. The investigators plan to follow-up with the cohort at 1 year.

Although exciting, these early results warrant caution, said Dr. Schneier. “On the one hand, this is a sample of people who have struggled for a long time and have failed previous therapies, so that’s good. But on the other hand, it’s an open trial with no placebo group, and everyone has high expectations, so we don’t know how much of a placebo effect there was.”

Most adverse events, including headaches and fatigue, were mild and resolved within the first week after dosing, and there were no serious adverse events.

Based on these findings, Dr. Schneier said controlled trials of psilocybin in BDD are warranted.
 

Need for scientific rigor

Commenting on the research, Charles B. Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, University of Texas at Austin, said while promising, psilocybin is “not for everyone” and patients need to be closely screened.

University of Texas at Austin

“We want to know their medical history and if they have a family history of schizophrenia or bipolar disorder. We don’t know whether these [psychedelic] medicines might trigger an episode.”

Dr. Nemeroff also noted there’s a risk of “troubling” side effects from the drug.

“My view is psilocybin clearly has therapeutic effects and we need to apply scientific rigor as we would any medicine in order to determine the risk/benefit ratio,” said Dr. Nemeroff, who was not associated with this psilocybin trial.

In addition, psilocybin is being tested in conditions other than BDD and major depression, including anorexia nervosa, postpartum depression, and alcohol use disorder, he added.

The study received funding from COMPASS Pathways PLC.

Dr. Nemeroff reports he has received research support from the NIH and Stanley Medical Research Institute; served as a consultant for Bracket (Clintara), Fortress Biotech, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Sunovion Pharmaceuticals, Taisho Pharmaceuticals, Takeda, TC MSO, and Xhale; served on scientific advisory boards for the American Foundation for Suicide Prevention, the Anxiety and Depression Association of America, Bracket (Clintara), Brain and Behavior Research Foundation, Laureate Institute for Brain Research, Skyland Trail, and Xhale; is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, OPKO Health, Seattle Genetics, and Xhale; serves on the board of directors for the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, and Gratitude America; has received income or equity of $10,000 or more from American Psychiatric Publishing, Bracket (Clintara), Magstim, CME Outfitters, and Intra-Cellular Therapies; and holds patents on a method and devices for transdermal delivery of lithium and a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay.

A version of this article first appeared on Medscape.com.

WASHINGTON – Psilocybin is safe and effective in patients with body dysmorphic disorder (BDD), preliminary findings of a small pilot study show.

“The results suggest that psilocybin appears to be relatively safe and potentially helpful for people with BDD, and that it has a broader scope than just depression,” study investigator Franklin Schneier, MD, codirector of the Anxiety Disorders Clinic, New York State Psychiatric Institute, and special lecturer in psychiatry at Columbia University Medical Center in New York City, told this news organization.

So far, psilocybin has mostly been examined in clinical trials among patients with major depression. Dr. Schneier said he is aware of only a single case in the literature of its use in BDD: a patient who self-treated with psilocybin and reported symptom improvement.

The current study was presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Few treatment options

Patients with BDD are preoccupied with a body part they perceive as ugly or defective, “and not just mildly so,” said Dr. Schneier. “It bothers them to the extreme such that they may obsess about it on and off all day long.”

Such patients may engage in compulsive behaviors like constantly checking themselves in the mirror, and going to great lengths to conceal the body part they feel is defective. “They often seek out cosmetic procedures that objectively aren’t warranted,” said Dr. Schneier.

BDD patients often have comorbid depression, and many attempt suicide. As with other anxiety and depressive disorders, BDD is twice as prevalent in women vs. men, said Dr. Schneier.

Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are the only approved therapies for BDD.

The investigators thought there may be a good chance BDD patients could benefit from psilocybin. Psilocybin alters bodily self-awareness, which “might shake up people’s beliefs about their abnormal body perceptions,” said Dr. Schneier.

There’s also some suggestion that psilocybin relaxes inflexible thinking, he added. “People with BDD have very rigid beliefs about their body distortions that aren’t easily swayed by logic.”

The study included 12 adults (8 women, 4 men) with a mean age of 34 years and moderate to severe BDD who failed at least one SSRI course and had had BDD for an average of 21 years.

Participants had preliminary sessions with a therapist familiar with psilocybin who prepared them psychologically and discussed what to expect from the experience. On the day of the intervention, subjects took a single 25 mg oral dose of synthetic psilocybin in a comfortable setting.

Therapists were present for the next 8 hours to answer questions and support subjects through the experience.
 

High response rate

The primary efficacy outcome was change in the BDD Yale-Brown Obsessive Compulsive Disorder Scale Modified (BDD-YBOCS) total score.

The mean baseline BDD-YBOCS score was 29.17. Researchers regularly assessed this score in the following weeks.

At 12 weeks, BDD-YBOCS scores decreased significantly from baseline (P < .001) with a large effect size (partial eta squared = .54).

However, said Dr. Schneier, what really stood out was the proportion of responders. At week 12, seven (58%) of the 12 participants were responders, as defined by a 30% or greater decrease in the BDD-YBOCS score. Of these, three were “almost symptom-free,” he added.

A number of secondary outcomes, including conviction of belief, disability, and negative affect, also significantly improved.

It’s too early to determine if additional treatment is required. The investigators plan to follow-up with the cohort at 1 year.

Although exciting, these early results warrant caution, said Dr. Schneier. “On the one hand, this is a sample of people who have struggled for a long time and have failed previous therapies, so that’s good. But on the other hand, it’s an open trial with no placebo group, and everyone has high expectations, so we don’t know how much of a placebo effect there was.”

Most adverse events, including headaches and fatigue, were mild and resolved within the first week after dosing, and there were no serious adverse events.

Based on these findings, Dr. Schneier said controlled trials of psilocybin in BDD are warranted.
 

Need for scientific rigor

Commenting on the research, Charles B. Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, University of Texas at Austin, said while promising, psilocybin is “not for everyone” and patients need to be closely screened.

University of Texas at Austin

“We want to know their medical history and if they have a family history of schizophrenia or bipolar disorder. We don’t know whether these [psychedelic] medicines might trigger an episode.”

Dr. Nemeroff also noted there’s a risk of “troubling” side effects from the drug.

“My view is psilocybin clearly has therapeutic effects and we need to apply scientific rigor as we would any medicine in order to determine the risk/benefit ratio,” said Dr. Nemeroff, who was not associated with this psilocybin trial.

In addition, psilocybin is being tested in conditions other than BDD and major depression, including anorexia nervosa, postpartum depression, and alcohol use disorder, he added.

The study received funding from COMPASS Pathways PLC.

Dr. Nemeroff reports he has received research support from the NIH and Stanley Medical Research Institute; served as a consultant for Bracket (Clintara), Fortress Biotech, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Sunovion Pharmaceuticals, Taisho Pharmaceuticals, Takeda, TC MSO, and Xhale; served on scientific advisory boards for the American Foundation for Suicide Prevention, the Anxiety and Depression Association of America, Bracket (Clintara), Brain and Behavior Research Foundation, Laureate Institute for Brain Research, Skyland Trail, and Xhale; is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, OPKO Health, Seattle Genetics, and Xhale; serves on the board of directors for the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, and Gratitude America; has received income or equity of $10,000 or more from American Psychiatric Publishing, Bracket (Clintara), Magstim, CME Outfitters, and Intra-Cellular Therapies; and holds patents on a method and devices for transdermal delivery of lithium and a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay.

A version of this article first appeared on Medscape.com.

A new study identifies specific brain regions involved in treatment response in bipolar disorder (BD) and borderline personality disorder (BPD), potentially paving the way for more targeted treatment.

In a meta-analysis of 34 studies that used neuroimaging to investigate changes in brain activation following psychotherapy and pharmacotherapy for BD and BPD, investigators found most brain regions showing abnormal activation in both conditions improved after treatment. In particular, changes in brain activity after psychotherapy were found primarily in the frontal areas, whereas pharmacotherapy largely altered the limbic areas.

“This study can help clinicians with clinical prediction of treatment efficacy between BD and BPD and clarify the neural mechanism of treatment for these two diseases,” senior investigator Xiaoming Li, PhD, professor, department of medical psychology, Anhui Medical University, Hefei, China, told this news organization.

“It may also contribute to the identification of more accurate neuroimaging biomarkers for treatment of the two disorders and to the finding of more effective therapy,” Dr. Li said.

The study was published online in the Journal of Clinical Psychiatry.
 

Blurred boundary

Dr. Li called BDs and BPDs “difficult to diagnose and differentiate,” noting that the comorbidity rate is “very high.” Underestimating the boundary between BD and BPD “increases the risk of improper or harmful drug exposure,” since mood stabilizing drugs are “considered to be the key therapeutic intervention for BD, while psychotherapy is the key treatment for BPD.”

The “blurred boundary between BD and BPD is one of the reasons it is important to study the relationship between these two diseases,” the authors said.

Previous studies comparing the relationship between BD and BPD “did not explore the similarities and differences in brain mechanisms between these two disorders after treatment,” they pointed out.

Patients with BD have a different disease course and response to therapy, compared to patient with BPD patients. “Misdiagnosis may result in the patients receiving ineffective treatment, so it is particularly important to explore the neural mechanisms of the treatment of these two diseases,” Dr. Li said.

To investigate, the researchers used activation likelihood estimation (ALE) – a technique that examines coordinates of neuroimaging data gleaned from published studies – after searching several databases from inception until June 2021.

This approach was used to “evaluate the similarities and differences in the activation of different brain regions in patients with BD and BPD after treatment with psychotherapy and drug therapy.”

Studies were required to focus on patients with a clinical diagnosis of BD or BPD; neuroimaging studies using functional MRI; coordinates of the peak activations in the stereotactic space of the Montreal Neurologic Institute or Talairach; treatment (pharmacologic or psychological) for patients with BD or BPD; and results of changes in brain activation after treatment, relative to a before-treatment condition.

Of 1,592 records, 34 studies (n = 912 subjects) met inclusion criteria and were selected and used in extracting the activation coordinates. The researchers extracted a total of 186 activity increase points and 90 activity decrease points. After combining these calculations, they found 12 increased activation clusters and 2 decreased activation clusters.

Of the studies, 23 focused on BD and 11 on BPD; 14 used psychotherapy, 18 used drug therapy, and 2 used a combination of both approaches.
 

Normalizing activation levels

Both treatments were associated with convergent activity increases and decreases in several brain regions: the anterior cingulate cortex, medial frontal gyrus, inferior frontal gyrus, cingulate gyrus, parahippocampal gyrus, and the posterior cingulate cortex.

The researchers then examined studies based on treatment method – psychotherapy or pharmacotherapy and the effect on the two disorders.

“After psychotherapy, the frontal lobe and temporal lobe were the primary brain regions in which activation changed, indicating a top-down effect of this therapy type, while after drug therapy, the limbic area was the region in which activation changed, indicating a ‘bottom-up’ effect,” said Dr. Li.

Dr. Li cited previous research pointing to functional and structural abnormalities in both disorders – especially in the default mode network (DMN) and frontolimbic network.

In particular, alterations in the amygdala and the parahippocampal gyrus are reported more frequently in BPD than in BD, whereas dysfunctional frontolimbic brain regions seem to underlie the emotional dysfunction in BPD. Several studies have also associated the impulsivity of BD with dysfunctions in the interplay of cortical-limbic circuits.

Dr. Li said the study findings suggest “that treatment may change these brain activation levels by acting on the abnormal brain circuit, such as the DMN and the frontolimbic network so as to ‘normalize’ its activity and improve symptoms.”

Specifically, brain regions with abnormally increased activation “showed decreased activation after treatment, and brain regions with abnormally decreased activation showed increased activation after treatment.”
 

Discrete, overlapping mechanisms

Commenting on the study, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, said the study “provides additional support for the underlying neurobiological signature of bipolar disorder and a commonly encountered co-occurring condition – borderline personality disorder – having both discrete yet overlapping mechanisms.”

He found it interesting that “medications have a different principal target than psychosocial interventions, which has both academic and clinical implications.

“The academic implication is that we have reasons to believe that we will be in a position to parse the neurobiology of bipolar disorder or borderline personality disorder when we take an approach that isolates specific domains of psychopathology, which is what they [the authors] appear to be doing,” said Dr. McIntyre, who wasn’t associated with this research.  

In addition, “from the clinical perspective, this provides a rationale for why we should be integrating pharmacotherapy with psychotherapy in people who have comorbid conditions like borderline personality disorder, which affects 20% of people living with bipolar disorder and 60% to 70% have borderline traits,” he added.

The research was supported by the Anhui Natural Science Foundation and Grants for Scientific Research from Anhui Medical University. Dr. Li and coauthors declared no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific Corp.

A version of this article first appeared on Medscape.com.

A new study identifies specific brain regions involved in treatment response in bipolar disorder (BD) and borderline personality disorder (BPD), potentially paving the way for more targeted treatment.

In a meta-analysis of 34 studies that used neuroimaging to investigate changes in brain activation following psychotherapy and pharmacotherapy for BD and BPD, investigators found most brain regions showing abnormal activation in both conditions improved after treatment. In particular, changes in brain activity after psychotherapy were found primarily in the frontal areas, whereas pharmacotherapy largely altered the limbic areas.

“This study can help clinicians with clinical prediction of treatment efficacy between BD and BPD and clarify the neural mechanism of treatment for these two diseases,” senior investigator Xiaoming Li, PhD, professor, department of medical psychology, Anhui Medical University, Hefei, China, told this news organization.

“It may also contribute to the identification of more accurate neuroimaging biomarkers for treatment of the two disorders and to the finding of more effective therapy,” Dr. Li said.

The study was published online in the Journal of Clinical Psychiatry.
 

Blurred boundary

Dr. Li called BDs and BPDs “difficult to diagnose and differentiate,” noting that the comorbidity rate is “very high.” Underestimating the boundary between BD and BPD “increases the risk of improper or harmful drug exposure,” since mood stabilizing drugs are “considered to be the key therapeutic intervention for BD, while psychotherapy is the key treatment for BPD.”

The “blurred boundary between BD and BPD is one of the reasons it is important to study the relationship between these two diseases,” the authors said.

Previous studies comparing the relationship between BD and BPD “did not explore the similarities and differences in brain mechanisms between these two disorders after treatment,” they pointed out.

Patients with BD have a different disease course and response to therapy, compared to patient with BPD patients. “Misdiagnosis may result in the patients receiving ineffective treatment, so it is particularly important to explore the neural mechanisms of the treatment of these two diseases,” Dr. Li said.

To investigate, the researchers used activation likelihood estimation (ALE) – a technique that examines coordinates of neuroimaging data gleaned from published studies – after searching several databases from inception until June 2021.

This approach was used to “evaluate the similarities and differences in the activation of different brain regions in patients with BD and BPD after treatment with psychotherapy and drug therapy.”

Studies were required to focus on patients with a clinical diagnosis of BD or BPD; neuroimaging studies using functional MRI; coordinates of the peak activations in the stereotactic space of the Montreal Neurologic Institute or Talairach; treatment (pharmacologic or psychological) for patients with BD or BPD; and results of changes in brain activation after treatment, relative to a before-treatment condition.

Of 1,592 records, 34 studies (n = 912 subjects) met inclusion criteria and were selected and used in extracting the activation coordinates. The researchers extracted a total of 186 activity increase points and 90 activity decrease points. After combining these calculations, they found 12 increased activation clusters and 2 decreased activation clusters.

Of the studies, 23 focused on BD and 11 on BPD; 14 used psychotherapy, 18 used drug therapy, and 2 used a combination of both approaches.
 

Normalizing activation levels

Both treatments were associated with convergent activity increases and decreases in several brain regions: the anterior cingulate cortex, medial frontal gyrus, inferior frontal gyrus, cingulate gyrus, parahippocampal gyrus, and the posterior cingulate cortex.

The researchers then examined studies based on treatment method – psychotherapy or pharmacotherapy and the effect on the two disorders.

“After psychotherapy, the frontal lobe and temporal lobe were the primary brain regions in which activation changed, indicating a top-down effect of this therapy type, while after drug therapy, the limbic area was the region in which activation changed, indicating a ‘bottom-up’ effect,” said Dr. Li.

Dr. Li cited previous research pointing to functional and structural abnormalities in both disorders – especially in the default mode network (DMN) and frontolimbic network.

In particular, alterations in the amygdala and the parahippocampal gyrus are reported more frequently in BPD than in BD, whereas dysfunctional frontolimbic brain regions seem to underlie the emotional dysfunction in BPD. Several studies have also associated the impulsivity of BD with dysfunctions in the interplay of cortical-limbic circuits.

Dr. Li said the study findings suggest “that treatment may change these brain activation levels by acting on the abnormal brain circuit, such as the DMN and the frontolimbic network so as to ‘normalize’ its activity and improve symptoms.”

Specifically, brain regions with abnormally increased activation “showed decreased activation after treatment, and brain regions with abnormally decreased activation showed increased activation after treatment.”
 

Discrete, overlapping mechanisms

Commenting on the study, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, said the study “provides additional support for the underlying neurobiological signature of bipolar disorder and a commonly encountered co-occurring condition – borderline personality disorder – having both discrete yet overlapping mechanisms.”

He found it interesting that “medications have a different principal target than psychosocial interventions, which has both academic and clinical implications.

“The academic implication is that we have reasons to believe that we will be in a position to parse the neurobiology of bipolar disorder or borderline personality disorder when we take an approach that isolates specific domains of psychopathology, which is what they [the authors] appear to be doing,” said Dr. McIntyre, who wasn’t associated with this research.  

In addition, “from the clinical perspective, this provides a rationale for why we should be integrating pharmacotherapy with psychotherapy in people who have comorbid conditions like borderline personality disorder, which affects 20% of people living with bipolar disorder and 60% to 70% have borderline traits,” he added.

The research was supported by the Anhui Natural Science Foundation and Grants for Scientific Research from Anhui Medical University. Dr. Li and coauthors declared no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific Corp.

A version of this article first appeared on Medscape.com.

A new study identifies specific brain regions involved in treatment response in bipolar disorder (BD) and borderline personality disorder (BPD), potentially paving the way for more targeted treatment.

In a meta-analysis of 34 studies that used neuroimaging to investigate changes in brain activation following psychotherapy and pharmacotherapy for BD and BPD, investigators found most brain regions showing abnormal activation in both conditions improved after treatment. In particular, changes in brain activity after psychotherapy were found primarily in the frontal areas, whereas pharmacotherapy largely altered the limbic areas.

“This study can help clinicians with clinical prediction of treatment efficacy between BD and BPD and clarify the neural mechanism of treatment for these two diseases,” senior investigator Xiaoming Li, PhD, professor, department of medical psychology, Anhui Medical University, Hefei, China, told this news organization.

“It may also contribute to the identification of more accurate neuroimaging biomarkers for treatment of the two disorders and to the finding of more effective therapy,” Dr. Li said.

The study was published online in the Journal of Clinical Psychiatry.
 

Blurred boundary

Dr. Li called BDs and BPDs “difficult to diagnose and differentiate,” noting that the comorbidity rate is “very high.” Underestimating the boundary between BD and BPD “increases the risk of improper or harmful drug exposure,” since mood stabilizing drugs are “considered to be the key therapeutic intervention for BD, while psychotherapy is the key treatment for BPD.”

The “blurred boundary between BD and BPD is one of the reasons it is important to study the relationship between these two diseases,” the authors said.

Previous studies comparing the relationship between BD and BPD “did not explore the similarities and differences in brain mechanisms between these two disorders after treatment,” they pointed out.

Patients with BD have a different disease course and response to therapy, compared to patient with BPD patients. “Misdiagnosis may result in the patients receiving ineffective treatment, so it is particularly important to explore the neural mechanisms of the treatment of these two diseases,” Dr. Li said.

To investigate, the researchers used activation likelihood estimation (ALE) – a technique that examines coordinates of neuroimaging data gleaned from published studies – after searching several databases from inception until June 2021.

This approach was used to “evaluate the similarities and differences in the activation of different brain regions in patients with BD and BPD after treatment with psychotherapy and drug therapy.”

Studies were required to focus on patients with a clinical diagnosis of BD or BPD; neuroimaging studies using functional MRI; coordinates of the peak activations in the stereotactic space of the Montreal Neurologic Institute or Talairach; treatment (pharmacologic or psychological) for patients with BD or BPD; and results of changes in brain activation after treatment, relative to a before-treatment condition.

Of 1,592 records, 34 studies (n = 912 subjects) met inclusion criteria and were selected and used in extracting the activation coordinates. The researchers extracted a total of 186 activity increase points and 90 activity decrease points. After combining these calculations, they found 12 increased activation clusters and 2 decreased activation clusters.

Of the studies, 23 focused on BD and 11 on BPD; 14 used psychotherapy, 18 used drug therapy, and 2 used a combination of both approaches.
 

Normalizing activation levels

Both treatments were associated with convergent activity increases and decreases in several brain regions: the anterior cingulate cortex, medial frontal gyrus, inferior frontal gyrus, cingulate gyrus, parahippocampal gyrus, and the posterior cingulate cortex.

The researchers then examined studies based on treatment method – psychotherapy or pharmacotherapy and the effect on the two disorders.

“After psychotherapy, the frontal lobe and temporal lobe were the primary brain regions in which activation changed, indicating a top-down effect of this therapy type, while after drug therapy, the limbic area was the region in which activation changed, indicating a ‘bottom-up’ effect,” said Dr. Li.

Dr. Li cited previous research pointing to functional and structural abnormalities in both disorders – especially in the default mode network (DMN) and frontolimbic network.

In particular, alterations in the amygdala and the parahippocampal gyrus are reported more frequently in BPD than in BD, whereas dysfunctional frontolimbic brain regions seem to underlie the emotional dysfunction in BPD. Several studies have also associated the impulsivity of BD with dysfunctions in the interplay of cortical-limbic circuits.

Dr. Li said the study findings suggest “that treatment may change these brain activation levels by acting on the abnormal brain circuit, such as the DMN and the frontolimbic network so as to ‘normalize’ its activity and improve symptoms.”

Specifically, brain regions with abnormally increased activation “showed decreased activation after treatment, and brain regions with abnormally decreased activation showed increased activation after treatment.”
 

Discrete, overlapping mechanisms

Commenting on the study, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, said the study “provides additional support for the underlying neurobiological signature of bipolar disorder and a commonly encountered co-occurring condition – borderline personality disorder – having both discrete yet overlapping mechanisms.”

He found it interesting that “medications have a different principal target than psychosocial interventions, which has both academic and clinical implications.

“The academic implication is that we have reasons to believe that we will be in a position to parse the neurobiology of bipolar disorder or borderline personality disorder when we take an approach that isolates specific domains of psychopathology, which is what they [the authors] appear to be doing,” said Dr. McIntyre, who wasn’t associated with this research.  

In addition, “from the clinical perspective, this provides a rationale for why we should be integrating pharmacotherapy with psychotherapy in people who have comorbid conditions like borderline personality disorder, which affects 20% of people living with bipolar disorder and 60% to 70% have borderline traits,” he added.

The research was supported by the Anhui Natural Science Foundation and Grants for Scientific Research from Anhui Medical University. Dr. Li and coauthors declared no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific Corp.

A version of this article first appeared on Medscape.com.

BOSTON – The neurologic symptoms of long COVID appear to be explained by a phenomenon known as antigenic imprinting, which involves a misdirected immune response to the SARS-CoV2 virus, according to a collaborative study presented at the 2023 annual meeting of the American Academy of Neurology.

Already documented in several other viral infections, such as influenza and human immunodeficiency virus, antigenic imprinting results in production of antibodies to previously encountered viral infections rather than to the immediate threat, according to Marianna Spatola, MD, PhD, a research fellow at the Ragon Institute, Harvard University, Cambridge, Mass.
 

Original antigenic sin

In the case of persistent neurologic symptoms after COVID, a condition known as neuroPASC (neurological postacute sequelae of SARS-CoV2 infection), antibodies produced for previously encountered coronaviruses rather than for SARS-CoV2 might explain most or all cases, according to the data Dr. Spatola presented.

The evidence for this explanation was drawn from a study of 112 patients evaluated months after an acute episode of COVID-19. Of these, 18 patients had persistent neurologic dysfunction. When compared with the 94 whose infection resolved without sequelae, the patients with prolonged neurologic impairments had relatively low systemic antibody response to SARS-CoV2. However, they showed relatively high antibody responses against other coronaviruses.

This is a pattern consistent with antigenic imprinting, a concept first described more than 60 years ago as original antigenic sin. When the immune system becomes imprinted with an antigen from the first encountered virus from a family of pathogens, it governs all subsequent antibody responses, according to several published studies that have described and evaluated this concept.
 

Additional evidence

In Dr. Spatola’s study, other differences, particularly in regard to the cerebrospinal fluid (CSF), further supported the role of antigenic imprinting as a cause of neuroPASC. For one, those with elevated immune responses to other common coronaviruses rather than SARS-CoV2 in the CSF relative to the periphery were more likely to have a bad outcome in regard to neurologic symptoms.

Moreover, the CSF in neuroPASC patients “was characterized by increased IgG1 and absence of IgM, suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier rather than through intrathecal synthesis,” Dr. Spatola reported.

In the case of COVID-19, the propensity for antigenic imprinting is not difficult to understand.

“The common cold coronaviruses are pretty similar to SARS-CoV2, but they are not exactly the same,” Dr. Spatola said. Her work and studies by others suggest that when antigenic imprinting occurs, “it prevents full maturation of the antibody response.”

NeuroPASC is one of many manifestations of long COVID, but Dr. Spatola pointed out that the immune response in the CSF is unique and the causes of prolonged neurologic impairment after COVID-19 are likely to involve different mechanisms than other long-COVID symptoms.

“Antibodies in the brain are functionally different,” said Dr. Spatola, noting for example that antibody-directed defenses against viral threats show a greater relative reliance on phagocytosis. This might become important in the development of therapeutics for neurologic symptoms of long COVID.
 

A different phenomenon

The manifestations of neuroPASC are heterogeneous and can include confusion, cognitive dysfunction, headache, encephalitis, and other impairments. Neurologic symptoms occur during acute SARS-CoV2 infections, but neuroPASC appears to be a different phenomenon. These symptoms, which develop after the initial respiratory disease has resolved, were attributed by Dr. Spatola to persistent inflammation that is not necessarily directly related to ongoing infection.

“The reason why some patients develop neuroPASC is unknown, but I think the evidence has pointed to a role for the immune system rather than the virus itself,” Dr. Spatola said.

Currently, neuroPASC is a clinical diagnosis but Dr. Spatola and her coinvestigators are conducting research to identify biomarkers. A viable diagnostic test is not expected imminently. They have identified 150 different features with potential relevance to neuroPASC.

In their comparison of those who did relative to those who did not develop neuroPASC, the initial studies were undertaken 2-4 months after the acute COVID-19 symptoms had resolved. The patients with neuroPASC and those without neurologic sequelae have now been followed for 6-8 months, which Dr. Spatola said was too short to draw firm conclusions about outcomes.
 

An evolving concept

Despite the small sample size of this study, these are “very interesting data” for considering the pathogenesis of neuroPASC, which is “a concept that is still evolving,” according to Natalia S. Rost, MD, chief of the stroke division, department of neurology, Massachusetts General Hospital, Boston.

Applied to SARS-CoV2, the concept of original antigenic sin “is new” but Dr. Rost said that it might help differentiate neuroPASC from acute neurologic symptoms of COVID-19, which include stroke. She indicated that the work performed by Dr. Spatola and others might eventually explain the pathology while leading to treatment strategies. She cautioned that the concepts explored in this study “need to be further developed” through larger sample sizes and the exploration of other variables that support the hypothesis.

Dr. Spatola and Dr. Rost report no potential conflicts of interest.

BOSTON – The neurologic symptoms of long COVID appear to be explained by a phenomenon known as antigenic imprinting, which involves a misdirected immune response to the SARS-CoV2 virus, according to a collaborative study presented at the 2023 annual meeting of the American Academy of Neurology.

Already documented in several other viral infections, such as influenza and human immunodeficiency virus, antigenic imprinting results in production of antibodies to previously encountered viral infections rather than to the immediate threat, according to Marianna Spatola, MD, PhD, a research fellow at the Ragon Institute, Harvard University, Cambridge, Mass.
 

Original antigenic sin

In the case of persistent neurologic symptoms after COVID, a condition known as neuroPASC (neurological postacute sequelae of SARS-CoV2 infection), antibodies produced for previously encountered coronaviruses rather than for SARS-CoV2 might explain most or all cases, according to the data Dr. Spatola presented.

The evidence for this explanation was drawn from a study of 112 patients evaluated months after an acute episode of COVID-19. Of these, 18 patients had persistent neurologic dysfunction. When compared with the 94 whose infection resolved without sequelae, the patients with prolonged neurologic impairments had relatively low systemic antibody response to SARS-CoV2. However, they showed relatively high antibody responses against other coronaviruses.

This is a pattern consistent with antigenic imprinting, a concept first described more than 60 years ago as original antigenic sin. When the immune system becomes imprinted with an antigen from the first encountered virus from a family of pathogens, it governs all subsequent antibody responses, according to several published studies that have described and evaluated this concept.
 

Additional evidence

In Dr. Spatola’s study, other differences, particularly in regard to the cerebrospinal fluid (CSF), further supported the role of antigenic imprinting as a cause of neuroPASC. For one, those with elevated immune responses to other common coronaviruses rather than SARS-CoV2 in the CSF relative to the periphery were more likely to have a bad outcome in regard to neurologic symptoms.

Moreover, the CSF in neuroPASC patients “was characterized by increased IgG1 and absence of IgM, suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier rather than through intrathecal synthesis,” Dr. Spatola reported.

In the case of COVID-19, the propensity for antigenic imprinting is not difficult to understand.

“The common cold coronaviruses are pretty similar to SARS-CoV2, but they are not exactly the same,” Dr. Spatola said. Her work and studies by others suggest that when antigenic imprinting occurs, “it prevents full maturation of the antibody response.”

NeuroPASC is one of many manifestations of long COVID, but Dr. Spatola pointed out that the immune response in the CSF is unique and the causes of prolonged neurologic impairment after COVID-19 are likely to involve different mechanisms than other long-COVID symptoms.

“Antibodies in the brain are functionally different,” said Dr. Spatola, noting for example that antibody-directed defenses against viral threats show a greater relative reliance on phagocytosis. This might become important in the development of therapeutics for neurologic symptoms of long COVID.
 

A different phenomenon

The manifestations of neuroPASC are heterogeneous and can include confusion, cognitive dysfunction, headache, encephalitis, and other impairments. Neurologic symptoms occur during acute SARS-CoV2 infections, but neuroPASC appears to be a different phenomenon. These symptoms, which develop after the initial respiratory disease has resolved, were attributed by Dr. Spatola to persistent inflammation that is not necessarily directly related to ongoing infection.

“The reason why some patients develop neuroPASC is unknown, but I think the evidence has pointed to a role for the immune system rather than the virus itself,” Dr. Spatola said.

Currently, neuroPASC is a clinical diagnosis but Dr. Spatola and her coinvestigators are conducting research to identify biomarkers. A viable diagnostic test is not expected imminently. They have identified 150 different features with potential relevance to neuroPASC.

In their comparison of those who did relative to those who did not develop neuroPASC, the initial studies were undertaken 2-4 months after the acute COVID-19 symptoms had resolved. The patients with neuroPASC and those without neurologic sequelae have now been followed for 6-8 months, which Dr. Spatola said was too short to draw firm conclusions about outcomes.
 

An evolving concept

Despite the small sample size of this study, these are “very interesting data” for considering the pathogenesis of neuroPASC, which is “a concept that is still evolving,” according to Natalia S. Rost, MD, chief of the stroke division, department of neurology, Massachusetts General Hospital, Boston.

Applied to SARS-CoV2, the concept of original antigenic sin “is new” but Dr. Rost said that it might help differentiate neuroPASC from acute neurologic symptoms of COVID-19, which include stroke. She indicated that the work performed by Dr. Spatola and others might eventually explain the pathology while leading to treatment strategies. She cautioned that the concepts explored in this study “need to be further developed” through larger sample sizes and the exploration of other variables that support the hypothesis.

Dr. Spatola and Dr. Rost report no potential conflicts of interest.

BOSTON – The neurologic symptoms of long COVID appear to be explained by a phenomenon known as antigenic imprinting, which involves a misdirected immune response to the SARS-CoV2 virus, according to a collaborative study presented at the 2023 annual meeting of the American Academy of Neurology.

Already documented in several other viral infections, such as influenza and human immunodeficiency virus, antigenic imprinting results in production of antibodies to previously encountered viral infections rather than to the immediate threat, according to Marianna Spatola, MD, PhD, a research fellow at the Ragon Institute, Harvard University, Cambridge, Mass.
 

Original antigenic sin

In the case of persistent neurologic symptoms after COVID, a condition known as neuroPASC (neurological postacute sequelae of SARS-CoV2 infection), antibodies produced for previously encountered coronaviruses rather than for SARS-CoV2 might explain most or all cases, according to the data Dr. Spatola presented.

The evidence for this explanation was drawn from a study of 112 patients evaluated months after an acute episode of COVID-19. Of these, 18 patients had persistent neurologic dysfunction. When compared with the 94 whose infection resolved without sequelae, the patients with prolonged neurologic impairments had relatively low systemic antibody response to SARS-CoV2. However, they showed relatively high antibody responses against other coronaviruses.

This is a pattern consistent with antigenic imprinting, a concept first described more than 60 years ago as original antigenic sin. When the immune system becomes imprinted with an antigen from the first encountered virus from a family of pathogens, it governs all subsequent antibody responses, according to several published studies that have described and evaluated this concept.
 

Additional evidence

In Dr. Spatola’s study, other differences, particularly in regard to the cerebrospinal fluid (CSF), further supported the role of antigenic imprinting as a cause of neuroPASC. For one, those with elevated immune responses to other common coronaviruses rather than SARS-CoV2 in the CSF relative to the periphery were more likely to have a bad outcome in regard to neurologic symptoms.

Moreover, the CSF in neuroPASC patients “was characterized by increased IgG1 and absence of IgM, suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier rather than through intrathecal synthesis,” Dr. Spatola reported.

In the case of COVID-19, the propensity for antigenic imprinting is not difficult to understand.

“The common cold coronaviruses are pretty similar to SARS-CoV2, but they are not exactly the same,” Dr. Spatola said. Her work and studies by others suggest that when antigenic imprinting occurs, “it prevents full maturation of the antibody response.”

NeuroPASC is one of many manifestations of long COVID, but Dr. Spatola pointed out that the immune response in the CSF is unique and the causes of prolonged neurologic impairment after COVID-19 are likely to involve different mechanisms than other long-COVID symptoms.

“Antibodies in the brain are functionally different,” said Dr. Spatola, noting for example that antibody-directed defenses against viral threats show a greater relative reliance on phagocytosis. This might become important in the development of therapeutics for neurologic symptoms of long COVID.
 

A different phenomenon

The manifestations of neuroPASC are heterogeneous and can include confusion, cognitive dysfunction, headache, encephalitis, and other impairments. Neurologic symptoms occur during acute SARS-CoV2 infections, but neuroPASC appears to be a different phenomenon. These symptoms, which develop after the initial respiratory disease has resolved, were attributed by Dr. Spatola to persistent inflammation that is not necessarily directly related to ongoing infection.

“The reason why some patients develop neuroPASC is unknown, but I think the evidence has pointed to a role for the immune system rather than the virus itself,” Dr. Spatola said.

Currently, neuroPASC is a clinical diagnosis but Dr. Spatola and her coinvestigators are conducting research to identify biomarkers. A viable diagnostic test is not expected imminently. They have identified 150 different features with potential relevance to neuroPASC.

In their comparison of those who did relative to those who did not develop neuroPASC, the initial studies were undertaken 2-4 months after the acute COVID-19 symptoms had resolved. The patients with neuroPASC and those without neurologic sequelae have now been followed for 6-8 months, which Dr. Spatola said was too short to draw firm conclusions about outcomes.
 

An evolving concept

Despite the small sample size of this study, these are “very interesting data” for considering the pathogenesis of neuroPASC, which is “a concept that is still evolving,” according to Natalia S. Rost, MD, chief of the stroke division, department of neurology, Massachusetts General Hospital, Boston.

Applied to SARS-CoV2, the concept of original antigenic sin “is new” but Dr. Rost said that it might help differentiate neuroPASC from acute neurologic symptoms of COVID-19, which include stroke. She indicated that the work performed by Dr. Spatola and others might eventually explain the pathology while leading to treatment strategies. She cautioned that the concepts explored in this study “need to be further developed” through larger sample sizes and the exploration of other variables that support the hypothesis.

Dr. Spatola and Dr. Rost report no potential conflicts of interest.

This discussion was recorded on April 6, 2023. This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining us today is Dr. Lewis Nelson, professor and chair of emergency medicine at Rutgers New Jersey Medical School and a certified medical toxicologist.

Today, we will be discussing an important and disturbing Gen Z trend circulating on social media, known as blackout rage gallon, or BORG.

Welcome, Lewis.

Lewis S. Nelson, MD: Thanks for having me.

Dr. Glatter: Thanks so much for joining us. This trend that’s been circulating on social media is really disturbing. It has elements that focus on binge drinking: Talking about taking a jug; emptying half of it out; and putting one fifth of vodka and some electrolytes, caffeine, or other things too is just incredibly disturbing. Teens and parents are looking at this. I’ll let you jump into the discussion.

Dr. Nelson: You’re totally right, it is disturbing. Binge drinking is a huge problem in this country in general. It’s a particular problem with young people – teenagers and young adults. I don’t think people appreciate the dangers associated with binge drinking, such as the amount of alcohol they consume and some of the unintended consequences of doing that.

To frame things quickly, we think there are probably around six people a day in the United States who die of alcohol poisoning. Alcohol poisoning basically is binge drinking to such an extent that you die of the alcohol itself. You’re not dying of a car crash or doing something that injures you. You’re dying of the alcohol. You’re drinking so much that your breathing slows, it stops, you have heart rhythm disturbances, and so on. It totals about 2,200 people a year in the United States.

Dr. Glatter: That’s alarming. For this trend, their argument is that half of the gallon is water. Therefore, I’m fine. I can drink it over 8-12 hours and it’s not an issue. How would you respond to that?

Dr. Nelson: Well, alcohol is alcohol. It’s all about how much you take in over what time period. I guess, in concept, it could be safer if you do it right. That’s not the way it’s been, so to speak, marketed on the various social media platforms. It’s meant to be a way to protect yourself from having your drink spiked or eating or ingesting contaminants from other people’s mouths when you share glasses or dip cups into communal pots like jungle juice or something.

Clearly, if you’re going to drink a large amount of alcohol over a short or long period of time, you do run the risk of having significant consequences, including bad decision-making if you’re just a little drunk all the way down to that of the complications you described about alcohol poisoning.

Dr. Glatter: There has been a comment made that this could be a form of harm reduction. The point of harm reduction is that we run trials, we validate it, and we test it. This, certainly in my mind, is no form of true harm reduction. I think you would agree.

Dr. Nelson: Many things that are marketed as harm reduction aren’t. There could be some aspects of this that could be considered harm reduction. You may believe – and there’s no reason not to – that protecting your drink is a good idea. If you’re at a bar and you leave your glass open and somebody put something in it, you can be drugged. Drug-facilitated sexual assault, for example, is a big issue. That means you have to leave your glass unattended. If you tend to your glass, it’s probably fine. One of the ways of harm reduction they mention is that by having a cap and having this bottle with you at all times, that can’t happen.

Now, in fairness, by far the drug most commonly associated with sexual assault is alcohol. It’s not gamma-hydroxybutyrate or ketamine. It’s not the other things that people are concerned about. Those happen, but those are small problems in the big picture. It’s drinking too much.

A form of harm reduction that you can comment on perhaps is that you make this drink concoction yourself, so you know what is in there. You can take that bottle, pour out half the water, and fill up the other half with water and nobody’s going to know. More likely, the way they say you should do it is you take your gallon jug, you pour it out, and you fill it up with one fifth of vodka.

One fifth of vodka is the same amount of volume as a bottle of wine. At 750 mL, that’s a huge amount of alcohol. If you measure the number of shots in that bottle, it’s about 17 shots. Even if you drink that over 6 hours, that’s still several shots an hour. That’s a large amount of alcohol. You might do two or three shots once and then not drink for a few hours. To sit and drink two or three shots an hour for 6 hours, that’s just an exceptional amount of alcohol.

They flavorize it and add caffeine, which only adds to the risk. It doesn’t make it in any way safer. With the volume, 1 gal of water or equivalent over a short period of time in and of itself could be a problem. There’s a large amount of mismessaging here. Whether something’s harm reduction, it could flip around to be easily construed or understood as being harmful.

Not to mention, the idea that when you make something safer, one of the unintended consequences of harm reduction is what we call risk compensation. This is best probably described as what’s called the Peltzman effect. The way that we think about airbags and seatbelts is that they’re going to reduce car crash deaths; and they do, but people drive faster and more recklessly because they know they’re safe.

This is a well-described problem in epidemiology: You expect a certain amount of harm reduction through some implemented process, but you don’t meet that because people take increased risks.

Dr. Glatter: Right. The idea of not developing a hangover is common among many teens and 20-somethings, thinking that because there’s hydration there, because half of it is water, it’s just not going to happen. There’s your “harm reduction,” but your judgment’s impaired. It’s day drinking at its best, all day long. Then someone has the idea to get behind the wheel. These are the disastrous consequences that we all fear.

Dr. Nelson: There is a great example, perhaps of an unintended consequence of harm reduction. By putting caffeine in it, depending on how much caffeine you put in, some of these mixtures can have up to 1,000 mg of caffeine. Remember, a cup of coffee is about 1-200 mg, so you’re talking about several cups of coffee. The idea is that you will not be able to sense, as you normally do, how drunk you are. You’re not going to be a sleepy drunk, you’re going to be an awake drunk.

The idea that you’re going to have to drive so you’re going to drink a strong cup of black coffee before you go driving, you’re not going to drive any better. I can assure you that. You’re going to be more awake, perhaps, and not fall asleep at the wheel, but you’re still going to have psychomotor impairment. Your judgment is going to be impaired. There’s nothing good that comes with adding caffeine except that you’re going to be awake.

From a hangover perspective, there are many things that we’ve guessed at or suggested as either prevention or cures for hangovers. I don’t doubt that you’re going to have some volume depletion if you drink a large amount of alcohol. Alcohol’s a diuretic, so you’re going to lose more volume than you bring in.

Hydrating is probably always a good idea, but there is hydrating and then there’s overhydrating. We don’t need volumes like that. If you drink a cup or two of water, you’re probably fine. You don’t need to drink half a gallon of water. That can lead to problems like delusional hyponatremia, and so forth. There’s not any clear benefit to doing it.

If you want to prevent a hangover, one of the ways you might do it is by using vodka. There are nice data that show that clear alcohols typically, particularly vodka, don’t have many of the congeners that make the specific forms of alcohol what they are. Bourbon smells and tastes like bourbon because of these little molecules, these alkalis and ketones and amino acids and things that make it taste and smell the way it does. That’s true for all the other alcohols.

Vodka has the least amount of that. Even wine and beer have those in them, but vodka is basically alcohol mixed with water. It’s probably the least hangover-prone of all the alcohols; but still, if you drink a lot of vodka, you’re going to have a hangover. It’s just a dose-response curve to how much alcohol you drink, to how drunk you get, and to how much of a hangover you’re going to have.

Dr. Glatter: The hangover is really what it’s about because people want to be functional the next day. There are many companies out there that market hangover remedies, but people are using this as the hangover remedy in a way that’s socially accepted. That’s a good point you make.

The question is how do we get the message out to parents and teens? What’s the best way you feel to really sound the alarm here?

Dr. Nelson: These are challenging issues. We face this all the time with all the sorts of social media in particular. Most parents are not as savvy on social media as their kids are. You have to know what your children are doing. You should know what they’re listening to and watching. You do have to pay attention to the media directed at parents that will inform you a little bit about what your kids are doing. You have to talk with your kids and make sure they understand what it is that they’re doing.

We do this with our kids for some things. Hopefully, we talk about drinking, smoking, sex, and other things with our children (like driving if they get to that stage) and make sure they understand what the risks are and how to mitigate those risks. Being an attentive parent is part of it.

Sometimes you need outside messengers to do it. We’d like to believe that these social media companies are able to police themselves – at least they pay lip service to the fact they do. They have warnings that they’ll take things down that aren’t socially appropriate. Whether they do or not, I don’t know, because you keep seeing things about BORG on these media sites. If they are doing it, they’re not doing it efficiently or quickly enough.

Dr. Glatter: There has to be some censorship. These are young persons who are impressionable, who have developing brains, who are looking at this, thinking that if it’s out there on social media, such as TikTok or Instagram, then it’s okay to do so. That message has to be driven home.

Dr. Nelson: That’s a great point, and it’s tough. We know there’s been debate over the liability of social media or what they post, and whether or not they should be held liable like a more conventional media company or not. That’s politics and philosophy, and we’re probably not going to solve it here.

All these things wind up going viral and there’s probably got to be some filter on things that go viral. Maybe they need to have a bit more attentiveness to that when those things start happening. Now, clearly not every one of these is viral. When you think about some of the challenges we’ve seen in the past, such as the Tide Pod challenge and cinnamon challenge, some of these things could be quickly figured out to be dangerous.

I remember that the ice bucket challenge for amyotrophic lateral sclerosis was pretty benign. You pour a bucket of water over your head, and people aren’t really getting hurt. That’s fun and good, and let people go out and do that. That could pass through the filter. When you start to see people drinking excessive amounts of alcohol, it doesn’t take an emergency physician to know that’s not a good thing. Any parent should know that if my kid drinks half a bottle or a bottle of vodka over a short period of time, that just can’t be okay.

Dr. Glatter: It’s a public health issue. That’s what we need to elevate it to because ultimately that’s what it impacts: welfare and safety.

Speaking of buckets, there’s a new bucket challenge, wherein unsuspecting people have a bucket put on their head, can’t breathe, and then pass out. There’s been a number of these reported and actually filmed on social media. Here’s another example of dangerous types of behavior that essentially are a form of assault. Unsuspecting people suffer injuries from young children and teens trying to play pranks.

Again, had there not been this medium, we wouldn’t necessarily see the extent of the injuries. I guess going forward, the next step would be to send a message to colleges that there should be some form of warning if this trend is seen, at least from a public health standpoint.

Dr. Nelson: Education is a necessary thing to do, but it’s almost never the real solution to a problem. We can educate people as best we can that they need to do things right. At some point, we’re going to need to regulate it or manage it somehow.

Whether it’s through a carrot or a stick approach, or whether you want to give people kudos for doing the right thing or punish them for doing something wrong, that’s a tough decision to make and one that is going to be made by a parent or guardian, a school official, or law enforcement. Somehow, we have to figure out how to make this happen.

There’s not going to be a single size that fits all for this. At some level, we have to do something to educate and regulate. The balance between those two things is going to be political and philosophical in nature.

Dr. Glatter: Right, and the element of peer pressure and conformity in this is really part of the element. If we try to remove that aspect of it, then often these trends would go away. That aspect of conformity and peer pressure is instrumental in fueling these trends. Maybe we can make a full gallon of water be the trend without any alcohol in there.

Dr. Nelson: We say water is only water, but as a medical toxicologist, I can tell you that one of the foundations in medical toxicology is that everything is toxic. It’s just the dose that determines the toxicity. Oxygen is toxic, water is toxic. Everything’s toxic if you take enough of it.

We know that whether it’s psychogenic or intentional, polydipsia by drinking excessive amounts of water, especially without electrolytes, is one of the reasons they say you should add electrolytes. That’s all relative as well, because depending on the electrolyte and how much you put in and things like that, that could also become dangerous. Drinking excessive amounts of water like they’re suggesting, which sounds like a good thing to prevent hangover and so on, can in and of itself be a problem too.

Dr. Glatter: Right, and we know that there’s no magic bullet for a hangover. Obviously, abstinence is the only thing that truly works.

Dr. Nelson: Or moderation.

Dr. Glatter: Until research proves further.

Thank you so much. You’ve made some really important points. Thank you for talking about the BORG phenomenon, how it relates to society in general, and what we can do to try to change people’s perception of alcohol and the bigger picture of binge drinking. I really appreciate it.

Dr. Nelson: Thanks, Rob, for having me. It’s an important topic and hopefully we can get a handle on this. I appreciate your time.

Dr. Glatter is an attending physician at Lenox Hill Hospital in New York City and assistant professor of emergency medicine at Hofstra University, Hempstead, N.Y. Dr. Nelson is professor and chair of the department of emergency medicine and chief of the division of medical toxicology at Rutgers New Jersey Medical School, Newark. He is a member of the board of directors of the American Board of Emergency Medicine, the Accreditation Council for Continuing Medical Education, and Association of Academic Chairs in Emergency Medicine and is past-president of the American College of Medical Toxicology. Dr. Glatter and Dr. Nelson disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

This discussion was recorded on April 6, 2023. This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining us today is Dr. Lewis Nelson, professor and chair of emergency medicine at Rutgers New Jersey Medical School and a certified medical toxicologist.

Today, we will be discussing an important and disturbing Gen Z trend circulating on social media, known as blackout rage gallon, or BORG.

Welcome, Lewis.

Lewis S. Nelson, MD: Thanks for having me.

Dr. Glatter: Thanks so much for joining us. This trend that’s been circulating on social media is really disturbing. It has elements that focus on binge drinking: Talking about taking a jug; emptying half of it out; and putting one fifth of vodka and some electrolytes, caffeine, or other things too is just incredibly disturbing. Teens and parents are looking at this. I’ll let you jump into the discussion.

Dr. Nelson: You’re totally right, it is disturbing. Binge drinking is a huge problem in this country in general. It’s a particular problem with young people – teenagers and young adults. I don’t think people appreciate the dangers associated with binge drinking, such as the amount of alcohol they consume and some of the unintended consequences of doing that.

To frame things quickly, we think there are probably around six people a day in the United States who die of alcohol poisoning. Alcohol poisoning basically is binge drinking to such an extent that you die of the alcohol itself. You’re not dying of a car crash or doing something that injures you. You’re dying of the alcohol. You’re drinking so much that your breathing slows, it stops, you have heart rhythm disturbances, and so on. It totals about 2,200 people a year in the United States.

Dr. Glatter: That’s alarming. For this trend, their argument is that half of the gallon is water. Therefore, I’m fine. I can drink it over 8-12 hours and it’s not an issue. How would you respond to that?

Dr. Nelson: Well, alcohol is alcohol. It’s all about how much you take in over what time period. I guess, in concept, it could be safer if you do it right. That’s not the way it’s been, so to speak, marketed on the various social media platforms. It’s meant to be a way to protect yourself from having your drink spiked or eating or ingesting contaminants from other people’s mouths when you share glasses or dip cups into communal pots like jungle juice or something.

Clearly, if you’re going to drink a large amount of alcohol over a short or long period of time, you do run the risk of having significant consequences, including bad decision-making if you’re just a little drunk all the way down to that of the complications you described about alcohol poisoning.

Dr. Glatter: There has been a comment made that this could be a form of harm reduction. The point of harm reduction is that we run trials, we validate it, and we test it. This, certainly in my mind, is no form of true harm reduction. I think you would agree.

Dr. Nelson: Many things that are marketed as harm reduction aren’t. There could be some aspects of this that could be considered harm reduction. You may believe – and there’s no reason not to – that protecting your drink is a good idea. If you’re at a bar and you leave your glass open and somebody put something in it, you can be drugged. Drug-facilitated sexual assault, for example, is a big issue. That means you have to leave your glass unattended. If you tend to your glass, it’s probably fine. One of the ways of harm reduction they mention is that by having a cap and having this bottle with you at all times, that can’t happen.

Now, in fairness, by far the drug most commonly associated with sexual assault is alcohol. It’s not gamma-hydroxybutyrate or ketamine. It’s not the other things that people are concerned about. Those happen, but those are small problems in the big picture. It’s drinking too much.

A form of harm reduction that you can comment on perhaps is that you make this drink concoction yourself, so you know what is in there. You can take that bottle, pour out half the water, and fill up the other half with water and nobody’s going to know. More likely, the way they say you should do it is you take your gallon jug, you pour it out, and you fill it up with one fifth of vodka.

One fifth of vodka is the same amount of volume as a bottle of wine. At 750 mL, that’s a huge amount of alcohol. If you measure the number of shots in that bottle, it’s about 17 shots. Even if you drink that over 6 hours, that’s still several shots an hour. That’s a large amount of alcohol. You might do two or three shots once and then not drink for a few hours. To sit and drink two or three shots an hour for 6 hours, that’s just an exceptional amount of alcohol.

They flavorize it and add caffeine, which only adds to the risk. It doesn’t make it in any way safer. With the volume, 1 gal of water or equivalent over a short period of time in and of itself could be a problem. There’s a large amount of mismessaging here. Whether something’s harm reduction, it could flip around to be easily construed or understood as being harmful.

Not to mention, the idea that when you make something safer, one of the unintended consequences of harm reduction is what we call risk compensation. This is best probably described as what’s called the Peltzman effect. The way that we think about airbags and seatbelts is that they’re going to reduce car crash deaths; and they do, but people drive faster and more recklessly because they know they’re safe.

This is a well-described problem in epidemiology: You expect a certain amount of harm reduction through some implemented process, but you don’t meet that because people take increased risks.

Dr. Glatter: Right. The idea of not developing a hangover is common among many teens and 20-somethings, thinking that because there’s hydration there, because half of it is water, it’s just not going to happen. There’s your “harm reduction,” but your judgment’s impaired. It’s day drinking at its best, all day long. Then someone has the idea to get behind the wheel. These are the disastrous consequences that we all fear.

Dr. Nelson: There is a great example, perhaps of an unintended consequence of harm reduction. By putting caffeine in it, depending on how much caffeine you put in, some of these mixtures can have up to 1,000 mg of caffeine. Remember, a cup of coffee is about 1-200 mg, so you’re talking about several cups of coffee. The idea is that you will not be able to sense, as you normally do, how drunk you are. You’re not going to be a sleepy drunk, you’re going to be an awake drunk.

The idea that you’re going to have to drive so you’re going to drink a strong cup of black coffee before you go driving, you’re not going to drive any better. I can assure you that. You’re going to be more awake, perhaps, and not fall asleep at the wheel, but you’re still going to have psychomotor impairment. Your judgment is going to be impaired. There’s nothing good that comes with adding caffeine except that you’re going to be awake.

From a hangover perspective, there are many things that we’ve guessed at or suggested as either prevention or cures for hangovers. I don’t doubt that you’re going to have some volume depletion if you drink a large amount of alcohol. Alcohol’s a diuretic, so you’re going to lose more volume than you bring in.

Hydrating is probably always a good idea, but there is hydrating and then there’s overhydrating. We don’t need volumes like that. If you drink a cup or two of water, you’re probably fine. You don’t need to drink half a gallon of water. That can lead to problems like delusional hyponatremia, and so forth. There’s not any clear benefit to doing it.

If you want to prevent a hangover, one of the ways you might do it is by using vodka. There are nice data that show that clear alcohols typically, particularly vodka, don’t have many of the congeners that make the specific forms of alcohol what they are. Bourbon smells and tastes like bourbon because of these little molecules, these alkalis and ketones and amino acids and things that make it taste and smell the way it does. That’s true for all the other alcohols.

Vodka has the least amount of that. Even wine and beer have those in them, but vodka is basically alcohol mixed with water. It’s probably the least hangover-prone of all the alcohols; but still, if you drink a lot of vodka, you’re going to have a hangover. It’s just a dose-response curve to how much alcohol you drink, to how drunk you get, and to how much of a hangover you’re going to have.

Dr. Glatter: The hangover is really what it’s about because people want to be functional the next day. There are many companies out there that market hangover remedies, but people are using this as the hangover remedy in a way that’s socially accepted. That’s a good point you make.

The question is how do we get the message out to parents and teens? What’s the best way you feel to really sound the alarm here?

Dr. Nelson: These are challenging issues. We face this all the time with all the sorts of social media in particular. Most parents are not as savvy on social media as their kids are. You have to know what your children are doing. You should know what they’re listening to and watching. You do have to pay attention to the media directed at parents that will inform you a little bit about what your kids are doing. You have to talk with your kids and make sure they understand what it is that they’re doing.

We do this with our kids for some things. Hopefully, we talk about drinking, smoking, sex, and other things with our children (like driving if they get to that stage) and make sure they understand what the risks are and how to mitigate those risks. Being an attentive parent is part of it.

Sometimes you need outside messengers to do it. We’d like to believe that these social media companies are able to police themselves – at least they pay lip service to the fact they do. They have warnings that they’ll take things down that aren’t socially appropriate. Whether they do or not, I don’t know, because you keep seeing things about BORG on these media sites. If they are doing it, they’re not doing it efficiently or quickly enough.

Dr. Glatter: There has to be some censorship. These are young persons who are impressionable, who have developing brains, who are looking at this, thinking that if it’s out there on social media, such as TikTok or Instagram, then it’s okay to do so. That message has to be driven home.

Dr. Nelson: That’s a great point, and it’s tough. We know there’s been debate over the liability of social media or what they post, and whether or not they should be held liable like a more conventional media company or not. That’s politics and philosophy, and we’re probably not going to solve it here.

All these things wind up going viral and there’s probably got to be some filter on things that go viral. Maybe they need to have a bit more attentiveness to that when those things start happening. Now, clearly not every one of these is viral. When you think about some of the challenges we’ve seen in the past, such as the Tide Pod challenge and cinnamon challenge, some of these things could be quickly figured out to be dangerous.

I remember that the ice bucket challenge for amyotrophic lateral sclerosis was pretty benign. You pour a bucket of water over your head, and people aren’t really getting hurt. That’s fun and good, and let people go out and do that. That could pass through the filter. When you start to see people drinking excessive amounts of alcohol, it doesn’t take an emergency physician to know that’s not a good thing. Any parent should know that if my kid drinks half a bottle or a bottle of vodka over a short period of time, that just can’t be okay.

Dr. Glatter: It’s a public health issue. That’s what we need to elevate it to because ultimately that’s what it impacts: welfare and safety.

Speaking of buckets, there’s a new bucket challenge, wherein unsuspecting people have a bucket put on their head, can’t breathe, and then pass out. There’s been a number of these reported and actually filmed on social media. Here’s another example of dangerous types of behavior that essentially are a form of assault. Unsuspecting people suffer injuries from young children and teens trying to play pranks.

Again, had there not been this medium, we wouldn’t necessarily see the extent of the injuries. I guess going forward, the next step would be to send a message to colleges that there should be some form of warning if this trend is seen, at least from a public health standpoint.

Dr. Nelson: Education is a necessary thing to do, but it’s almost never the real solution to a problem. We can educate people as best we can that they need to do things right. At some point, we’re going to need to regulate it or manage it somehow.

Whether it’s through a carrot or a stick approach, or whether you want to give people kudos for doing the right thing or punish them for doing something wrong, that’s a tough decision to make and one that is going to be made by a parent or guardian, a school official, or law enforcement. Somehow, we have to figure out how to make this happen.

There’s not going to be a single size that fits all for this. At some level, we have to do something to educate and regulate. The balance between those two things is going to be political and philosophical in nature.

Dr. Glatter: Right, and the element of peer pressure and conformity in this is really part of the element. If we try to remove that aspect of it, then often these trends would go away. That aspect of conformity and peer pressure is instrumental in fueling these trends. Maybe we can make a full gallon of water be the trend without any alcohol in there.

Dr. Nelson: We say water is only water, but as a medical toxicologist, I can tell you that one of the foundations in medical toxicology is that everything is toxic. It’s just the dose that determines the toxicity. Oxygen is toxic, water is toxic. Everything’s toxic if you take enough of it.

We know that whether it’s psychogenic or intentional, polydipsia by drinking excessive amounts of water, especially without electrolytes, is one of the reasons they say you should add electrolytes. That’s all relative as well, because depending on the electrolyte and how much you put in and things like that, that could also become dangerous. Drinking excessive amounts of water like they’re suggesting, which sounds like a good thing to prevent hangover and so on, can in and of itself be a problem too.

Dr. Glatter: Right, and we know that there’s no magic bullet for a hangover. Obviously, abstinence is the only thing that truly works.

Dr. Nelson: Or moderation.

Dr. Glatter: Until research proves further.

Thank you so much. You’ve made some really important points. Thank you for talking about the BORG phenomenon, how it relates to society in general, and what we can do to try to change people’s perception of alcohol and the bigger picture of binge drinking. I really appreciate it.

Dr. Nelson: Thanks, Rob, for having me. It’s an important topic and hopefully we can get a handle on this. I appreciate your time.

Dr. Glatter is an attending physician at Lenox Hill Hospital in New York City and assistant professor of emergency medicine at Hofstra University, Hempstead, N.Y. Dr. Nelson is professor and chair of the department of emergency medicine and chief of the division of medical toxicology at Rutgers New Jersey Medical School, Newark. He is a member of the board of directors of the American Board of Emergency Medicine, the Accreditation Council for Continuing Medical Education, and Association of Academic Chairs in Emergency Medicine and is past-president of the American College of Medical Toxicology. Dr. Glatter and Dr. Nelson disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

This discussion was recorded on April 6, 2023. This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining us today is Dr. Lewis Nelson, professor and chair of emergency medicine at Rutgers New Jersey Medical School and a certified medical toxicologist.

Today, we will be discussing an important and disturbing Gen Z trend circulating on social media, known as blackout rage gallon, or BORG.

Welcome, Lewis.

Lewis S. Nelson, MD: Thanks for having me.

Dr. Glatter: Thanks so much for joining us. This trend that’s been circulating on social media is really disturbing. It has elements that focus on binge drinking: Talking about taking a jug; emptying half of it out; and putting one fifth of vodka and some electrolytes, caffeine, or other things too is just incredibly disturbing. Teens and parents are looking at this. I’ll let you jump into the discussion.

Dr. Nelson: You’re totally right, it is disturbing. Binge drinking is a huge problem in this country in general. It’s a particular problem with young people – teenagers and young adults. I don’t think people appreciate the dangers associated with binge drinking, such as the amount of alcohol they consume and some of the unintended consequences of doing that.

To frame things quickly, we think there are probably around six people a day in the United States who die of alcohol poisoning. Alcohol poisoning basically is binge drinking to such an extent that you die of the alcohol itself. You’re not dying of a car crash or doing something that injures you. You’re dying of the alcohol. You’re drinking so much that your breathing slows, it stops, you have heart rhythm disturbances, and so on. It totals about 2,200 people a year in the United States.

Dr. Glatter: That’s alarming. For this trend, their argument is that half of the gallon is water. Therefore, I’m fine. I can drink it over 8-12 hours and it’s not an issue. How would you respond to that?

Dr. Nelson: Well, alcohol is alcohol. It’s all about how much you take in over what time period. I guess, in concept, it could be safer if you do it right. That’s not the way it’s been, so to speak, marketed on the various social media platforms. It’s meant to be a way to protect yourself from having your drink spiked or eating or ingesting contaminants from other people’s mouths when you share glasses or dip cups into communal pots like jungle juice or something.

Clearly, if you’re going to drink a large amount of alcohol over a short or long period of time, you do run the risk of having significant consequences, including bad decision-making if you’re just a little drunk all the way down to that of the complications you described about alcohol poisoning.

Dr. Glatter: There has been a comment made that this could be a form of harm reduction. The point of harm reduction is that we run trials, we validate it, and we test it. This, certainly in my mind, is no form of true harm reduction. I think you would agree.

Dr. Nelson: Many things that are marketed as harm reduction aren’t. There could be some aspects of this that could be considered harm reduction. You may believe – and there’s no reason not to – that protecting your drink is a good idea. If you’re at a bar and you leave your glass open and somebody put something in it, you can be drugged. Drug-facilitated sexual assault, for example, is a big issue. That means you have to leave your glass unattended. If you tend to your glass, it’s probably fine. One of the ways of harm reduction they mention is that by having a cap and having this bottle with you at all times, that can’t happen.

Now, in fairness, by far the drug most commonly associated with sexual assault is alcohol. It’s not gamma-hydroxybutyrate or ketamine. It’s not the other things that people are concerned about. Those happen, but those are small problems in the big picture. It’s drinking too much.

A form of harm reduction that you can comment on perhaps is that you make this drink concoction yourself, so you know what is in there. You can take that bottle, pour out half the water, and fill up the other half with water and nobody’s going to know. More likely, the way they say you should do it is you take your gallon jug, you pour it out, and you fill it up with one fifth of vodka.

One fifth of vodka is the same amount of volume as a bottle of wine. At 750 mL, that’s a huge amount of alcohol. If you measure the number of shots in that bottle, it’s about 17 shots. Even if you drink that over 6 hours, that’s still several shots an hour. That’s a large amount of alcohol. You might do two or three shots once and then not drink for a few hours. To sit and drink two or three shots an hour for 6 hours, that’s just an exceptional amount of alcohol.

They flavorize it and add caffeine, which only adds to the risk. It doesn’t make it in any way safer. With the volume, 1 gal of water or equivalent over a short period of time in and of itself could be a problem. There’s a large amount of mismessaging here. Whether something’s harm reduction, it could flip around to be easily construed or understood as being harmful.

Not to mention, the idea that when you make something safer, one of the unintended consequences of harm reduction is what we call risk compensation. This is best probably described as what’s called the Peltzman effect. The way that we think about airbags and seatbelts is that they’re going to reduce car crash deaths; and they do, but people drive faster and more recklessly because they know they’re safe.

This is a well-described problem in epidemiology: You expect a certain amount of harm reduction through some implemented process, but you don’t meet that because people take increased risks.

Dr. Glatter: Right. The idea of not developing a hangover is common among many teens and 20-somethings, thinking that because there’s hydration there, because half of it is water, it’s just not going to happen. There’s your “harm reduction,” but your judgment’s impaired. It’s day drinking at its best, all day long. Then someone has the idea to get behind the wheel. These are the disastrous consequences that we all fear.

Dr. Nelson: There is a great example, perhaps of an unintended consequence of harm reduction. By putting caffeine in it, depending on how much caffeine you put in, some of these mixtures can have up to 1,000 mg of caffeine. Remember, a cup of coffee is about 1-200 mg, so you’re talking about several cups of coffee. The idea is that you will not be able to sense, as you normally do, how drunk you are. You’re not going to be a sleepy drunk, you’re going to be an awake drunk.

The idea that you’re going to have to drive so you’re going to drink a strong cup of black coffee before you go driving, you’re not going to drive any better. I can assure you that. You’re going to be more awake, perhaps, and not fall asleep at the wheel, but you’re still going to have psychomotor impairment. Your judgment is going to be impaired. There’s nothing good that comes with adding caffeine except that you’re going to be awake.

From a hangover perspective, there are many things that we’ve guessed at or suggested as either prevention or cures for hangovers. I don’t doubt that you’re going to have some volume depletion if you drink a large amount of alcohol. Alcohol’s a diuretic, so you’re going to lose more volume than you bring in.

Hydrating is probably always a good idea, but there is hydrating and then there’s overhydrating. We don’t need volumes like that. If you drink a cup or two of water, you’re probably fine. You don’t need to drink half a gallon of water. That can lead to problems like delusional hyponatremia, and so forth. There’s not any clear benefit to doing it.

If you want to prevent a hangover, one of the ways you might do it is by using vodka. There are nice data that show that clear alcohols typically, particularly vodka, don’t have many of the congeners that make the specific forms of alcohol what they are. Bourbon smells and tastes like bourbon because of these little molecules, these alkalis and ketones and amino acids and things that make it taste and smell the way it does. That’s true for all the other alcohols.

Vodka has the least amount of that. Even wine and beer have those in them, but vodka is basically alcohol mixed with water. It’s probably the least hangover-prone of all the alcohols; but still, if you drink a lot of vodka, you’re going to have a hangover. It’s just a dose-response curve to how much alcohol you drink, to how drunk you get, and to how much of a hangover you’re going to have.

Dr. Glatter: The hangover is really what it’s about because people want to be functional the next day. There are many companies out there that market hangover remedies, but people are using this as the hangover remedy in a way that’s socially accepted. That’s a good point you make.

The question is how do we get the message out to parents and teens? What’s the best way you feel to really sound the alarm here?

Dr. Nelson: These are challenging issues. We face this all the time with all the sorts of social media in particular. Most parents are not as savvy on social media as their kids are. You have to know what your children are doing. You should know what they’re listening to and watching. You do have to pay attention to the media directed at parents that will inform you a little bit about what your kids are doing. You have to talk with your kids and make sure they understand what it is that they’re doing.

We do this with our kids for some things. Hopefully, we talk about drinking, smoking, sex, and other things with our children (like driving if they get to that stage) and make sure they understand what the risks are and how to mitigate those risks. Being an attentive parent is part of it.

Sometimes you need outside messengers to do it. We’d like to believe that these social media companies are able to police themselves – at least they pay lip service to the fact they do. They have warnings that they’ll take things down that aren’t socially appropriate. Whether they do or not, I don’t know, because you keep seeing things about BORG on these media sites. If they are doing it, they’re not doing it efficiently or quickly enough.

Dr. Glatter: There has to be some censorship. These are young persons who are impressionable, who have developing brains, who are looking at this, thinking that if it’s out there on social media, such as TikTok or Instagram, then it’s okay to do so. That message has to be driven home.

Dr. Nelson: That’s a great point, and it’s tough. We know there’s been debate over the liability of social media or what they post, and whether or not they should be held liable like a more conventional media company or not. That’s politics and philosophy, and we’re probably not going to solve it here.

All these things wind up going viral and there’s probably got to be some filter on things that go viral. Maybe they need to have a bit more attentiveness to that when those things start happening. Now, clearly not every one of these is viral. When you think about some of the challenges we’ve seen in the past, such as the Tide Pod challenge and cinnamon challenge, some of these things could be quickly figured out to be dangerous.

I remember that the ice bucket challenge for amyotrophic lateral sclerosis was pretty benign. You pour a bucket of water over your head, and people aren’t really getting hurt. That’s fun and good, and let people go out and do that. That could pass through the filter. When you start to see people drinking excessive amounts of alcohol, it doesn’t take an emergency physician to know that’s not a good thing. Any parent should know that if my kid drinks half a bottle or a bottle of vodka over a short period of time, that just can’t be okay.

Dr. Glatter: It’s a public health issue. That’s what we need to elevate it to because ultimately that’s what it impacts: welfare and safety.

Speaking of buckets, there’s a new bucket challenge, wherein unsuspecting people have a bucket put on their head, can’t breathe, and then pass out. There’s been a number of these reported and actually filmed on social media. Here’s another example of dangerous types of behavior that essentially are a form of assault. Unsuspecting people suffer injuries from young children and teens trying to play pranks.

Again, had there not been this medium, we wouldn’t necessarily see the extent of the injuries. I guess going forward, the next step would be to send a message to colleges that there should be some form of warning if this trend is seen, at least from a public health standpoint.

Dr. Nelson: Education is a necessary thing to do, but it’s almost never the real solution to a problem. We can educate people as best we can that they need to do things right. At some point, we’re going to need to regulate it or manage it somehow.

Whether it’s through a carrot or a stick approach, or whether you want to give people kudos for doing the right thing or punish them for doing something wrong, that’s a tough decision to make and one that is going to be made by a parent or guardian, a school official, or law enforcement. Somehow, we have to figure out how to make this happen.

There’s not going to be a single size that fits all for this. At some level, we have to do something to educate and regulate. The balance between those two things is going to be political and philosophical in nature.

Dr. Glatter: Right, and the element of peer pressure and conformity in this is really part of the element. If we try to remove that aspect of it, then often these trends would go away. That aspect of conformity and peer pressure is instrumental in fueling these trends. Maybe we can make a full gallon of water be the trend without any alcohol in there.

Dr. Nelson: We say water is only water, but as a medical toxicologist, I can tell you that one of the foundations in medical toxicology is that everything is toxic. It’s just the dose that determines the toxicity. Oxygen is toxic, water is toxic. Everything’s toxic if you take enough of it.

We know that whether it’s psychogenic or intentional, polydipsia by drinking excessive amounts of water, especially without electrolytes, is one of the reasons they say you should add electrolytes. That’s all relative as well, because depending on the electrolyte and how much you put in and things like that, that could also become dangerous. Drinking excessive amounts of water like they’re suggesting, which sounds like a good thing to prevent hangover and so on, can in and of itself be a problem too.

Dr. Glatter: Right, and we know that there’s no magic bullet for a hangover. Obviously, abstinence is the only thing that truly works.

Dr. Nelson: Or moderation.

Dr. Glatter: Until research proves further.

Thank you so much. You’ve made some really important points. Thank you for talking about the BORG phenomenon, how it relates to society in general, and what we can do to try to change people’s perception of alcohol and the bigger picture of binge drinking. I really appreciate it.

Dr. Nelson: Thanks, Rob, for having me. It’s an important topic and hopefully we can get a handle on this. I appreciate your time.

Dr. Glatter is an attending physician at Lenox Hill Hospital in New York City and assistant professor of emergency medicine at Hofstra University, Hempstead, N.Y. Dr. Nelson is professor and chair of the department of emergency medicine and chief of the division of medical toxicology at Rutgers New Jersey Medical School, Newark. He is a member of the board of directors of the American Board of Emergency Medicine, the Accreditation Council for Continuing Medical Education, and Association of Academic Chairs in Emergency Medicine and is past-president of the American College of Medical Toxicology. Dr. Glatter and Dr. Nelson disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Regular meditation reduced depression by roughly 44% in adults with coronary artery disease who were involved in a cardiovascular rehabilitation program.

An increasing body of research supports the impact of psychological risk factors including stress, personality type, anger, and hostility on conditions such as depression and anxiety, but also social isolation and low socioeconomic status, Ana Luisa Vitorino Monteiro, MD, of the University of Lisbon said in a presentation at the annual congress of the European Association of Preventive Cardiology. In addition, “stress, anxiety, and depression deteriorate the cardiovascular (CV) system through psycho-neuro-immunoendocrinology system and behavioral pathways.”

Meditation as a tool for stress management has been gaining popularity, but its use as part of a CV rehabilitation program as a complementary therapy has not been well studied, she added.

Dr. Monteiro and colleagues recruited 80 adults with CAD who were undergoing CV rehabilitation to join a meditation program. Of these, 48 accepted (60%) and 40% declined. Those who accepted were part of an exercise-based CV rehabilitation program that met three times a week for at least 6 months. The mean age of the participants was 65 years, and 80% were male.

Participants were randomized to an intervention group with a weekly 90-minute session that included breathing and meditation for 1 month in addition to usual care, or to usual care in the rehabilitation program. Over the next 3 months, the intervention patients were encouraged to practice daily meditation for 20 minutes alone or using video support material, with a weekly follow-up phone call. Assessments of stress, anxiety, and depression took place at baseline and after 4 months using the Perceived Stress Scale, Beck Anxiety Inventory, Beck Depression Inventory, and HeartQoL questionnaire.

At 4 months, individuals in the meditation group had reduced depression levels significantly, by 44%, compared with controls (P < .001). Anxiety and stress decreased significantly, by 30% (P = .04) and 31% (P = .05), respectively. After 4 months, individuals in the control group were offered the opportunity to follow the meditation protocol.

In addition, “the emotional dimension of quality of life increased by 60% in the intervention group,” Dr. Monteiro noted. However, physical QoL did not change between groups.

The study was limited by the small sample size, and more research is needed in larger and more diverse populations, Dr. Monteiro said. However, the results support the value of meditation as an adjunct component of care for CAD patients in a long-term rehabilitation program.
 

Motivation makes a difference

The current study is important as an exploration of “a straightforward, simple, low-risk approach that could be an adjunct to benefit patients with serious cardiovascular disease,” Brian Olshansky, MD, a cardiologist at the University of Iowa, Iowa City, said in an interview.

“We have moved into a time of polypharmacy and multiple interventions for patients with underlying cardiovascular disease which, in many cases, have proven benefit but also potential adverse effects,” he said. “Engaging patients to participate in their health care, when there is serious underlying cardiovascular disease, has potential beneficial impact in many ways. Meditation is a low-risk, low-cost, potentially beneficial adjunct to standard medical therapy that may enhance psychological outcomes as shown here in this small study.”

However, “patients often rely on high-cost, potentially high-risk therapeutic interventions, expecting complete control of their problems without their own collaborative intervention,” he noted.

Dr. Olshansky said he was not surprised by any of the findings, and would have been surprised if meditation had failed to show any benefit for the study population.

“I am very pleased to see these results and would encourage meditation practice to be part of cardiovascular rehabilitation for motivated individuals,” he said. “What did surprise me was the adherence to the meditation protocol for those who participated. This represents a highly motivated group and it may be difficult to expect the same results in less motivated individuals.”

The current study has several strengths, including the use of controls and high rates of adherence to the protocol, said Dr. Olshansky. Other strengths include the standardized approach and the reasonable quality of the outcome measures, which showed a substantial benefit.

However, “this is a small study of motivated individuals of whom 80% were male,” and generalizability to other populations is unclear, Dr. Olshansky said. In addition, the racial mix was not described, and the severity of the underlying coronary artery disease and the therapies provided to these individuals is not detailed. A sicker population may not fare as well.”

The reasons for the benefits of meditation remain uncertain, Dr. Olshansky said. “It could be, specifically, that the meditation itself has physiological effects that ultimately translate into psychosocial benefit. However, those who enrolled and were interested may have derived a placebo effect. In any case, benefit was achieved, but the crossover benefit to the control group is unclear.

“In other words, the statistical approach to benefit is uncertain as to when it was measured, but presumably before the control group was allowed to engage in a meditation practice,” and the follow-up was short term, said Dr. Olshansky.
 

Data support patient engagement

The message to clinicians and patients: “Patients should be engaged in their own health care when it comes to rehabilitation for cardiovascular disease,” said Dr. Olshansky. “Motivated individuals who are educated about a meditative practice performed in a standardized way will have improvement most likely in their quality of life, and when it comes to measurements of depression, stress and anxiety.”

Although the mechanisms behind the benefits remain unclear, “having a standardized credible prescription for which patients can become intimately engaged is beneficial,” he added.

The study received no outside funding. Neither Dr. Monteiro nor Dr. Olshansky had any financial conflicts to disclose.


 

Regular meditation reduced depression by roughly 44% in adults with coronary artery disease who were involved in a cardiovascular rehabilitation program.

An increasing body of research supports the impact of psychological risk factors including stress, personality type, anger, and hostility on conditions such as depression and anxiety, but also social isolation and low socioeconomic status, Ana Luisa Vitorino Monteiro, MD, of the University of Lisbon said in a presentation at the annual congress of the European Association of Preventive Cardiology. In addition, “stress, anxiety, and depression deteriorate the cardiovascular (CV) system through psycho-neuro-immunoendocrinology system and behavioral pathways.”

Meditation as a tool for stress management has been gaining popularity, but its use as part of a CV rehabilitation program as a complementary therapy has not been well studied, she added.

Dr. Monteiro and colleagues recruited 80 adults with CAD who were undergoing CV rehabilitation to join a meditation program. Of these, 48 accepted (60%) and 40% declined. Those who accepted were part of an exercise-based CV rehabilitation program that met three times a week for at least 6 months. The mean age of the participants was 65 years, and 80% were male.

Participants were randomized to an intervention group with a weekly 90-minute session that included breathing and meditation for 1 month in addition to usual care, or to usual care in the rehabilitation program. Over the next 3 months, the intervention patients were encouraged to practice daily meditation for 20 minutes alone or using video support material, with a weekly follow-up phone call. Assessments of stress, anxiety, and depression took place at baseline and after 4 months using the Perceived Stress Scale, Beck Anxiety Inventory, Beck Depression Inventory, and HeartQoL questionnaire.

At 4 months, individuals in the meditation group had reduced depression levels significantly, by 44%, compared with controls (P < .001). Anxiety and stress decreased significantly, by 30% (P = .04) and 31% (P = .05), respectively. After 4 months, individuals in the control group were offered the opportunity to follow the meditation protocol.

In addition, “the emotional dimension of quality of life increased by 60% in the intervention group,” Dr. Monteiro noted. However, physical QoL did not change between groups.

The study was limited by the small sample size, and more research is needed in larger and more diverse populations, Dr. Monteiro said. However, the results support the value of meditation as an adjunct component of care for CAD patients in a long-term rehabilitation program.
 

Motivation makes a difference

The current study is important as an exploration of “a straightforward, simple, low-risk approach that could be an adjunct to benefit patients with serious cardiovascular disease,” Brian Olshansky, MD, a cardiologist at the University of Iowa, Iowa City, said in an interview.

“We have moved into a time of polypharmacy and multiple interventions for patients with underlying cardiovascular disease which, in many cases, have proven benefit but also potential adverse effects,” he said. “Engaging patients to participate in their health care, when there is serious underlying cardiovascular disease, has potential beneficial impact in many ways. Meditation is a low-risk, low-cost, potentially beneficial adjunct to standard medical therapy that may enhance psychological outcomes as shown here in this small study.”

However, “patients often rely on high-cost, potentially high-risk therapeutic interventions, expecting complete control of their problems without their own collaborative intervention,” he noted.

Dr. Olshansky said he was not surprised by any of the findings, and would have been surprised if meditation had failed to show any benefit for the study population.

“I am very pleased to see these results and would encourage meditation practice to be part of cardiovascular rehabilitation for motivated individuals,” he said. “What did surprise me was the adherence to the meditation protocol for those who participated. This represents a highly motivated group and it may be difficult to expect the same results in less motivated individuals.”

The current study has several strengths, including the use of controls and high rates of adherence to the protocol, said Dr. Olshansky. Other strengths include the standardized approach and the reasonable quality of the outcome measures, which showed a substantial benefit.

However, “this is a small study of motivated individuals of whom 80% were male,” and generalizability to other populations is unclear, Dr. Olshansky said. In addition, the racial mix was not described, and the severity of the underlying coronary artery disease and the therapies provided to these individuals is not detailed. A sicker population may not fare as well.”

The reasons for the benefits of meditation remain uncertain, Dr. Olshansky said. “It could be, specifically, that the meditation itself has physiological effects that ultimately translate into psychosocial benefit. However, those who enrolled and were interested may have derived a placebo effect. In any case, benefit was achieved, but the crossover benefit to the control group is unclear.

“In other words, the statistical approach to benefit is uncertain as to when it was measured, but presumably before the control group was allowed to engage in a meditation practice,” and the follow-up was short term, said Dr. Olshansky.
 

Data support patient engagement

The message to clinicians and patients: “Patients should be engaged in their own health care when it comes to rehabilitation for cardiovascular disease,” said Dr. Olshansky. “Motivated individuals who are educated about a meditative practice performed in a standardized way will have improvement most likely in their quality of life, and when it comes to measurements of depression, stress and anxiety.”

Although the mechanisms behind the benefits remain unclear, “having a standardized credible prescription for which patients can become intimately engaged is beneficial,” he added.

The study received no outside funding. Neither Dr. Monteiro nor Dr. Olshansky had any financial conflicts to disclose.


 

Regular meditation reduced depression by roughly 44% in adults with coronary artery disease who were involved in a cardiovascular rehabilitation program.

An increasing body of research supports the impact of psychological risk factors including stress, personality type, anger, and hostility on conditions such as depression and anxiety, but also social isolation and low socioeconomic status, Ana Luisa Vitorino Monteiro, MD, of the University of Lisbon said in a presentation at the annual congress of the European Association of Preventive Cardiology. In addition, “stress, anxiety, and depression deteriorate the cardiovascular (CV) system through psycho-neuro-immunoendocrinology system and behavioral pathways.”

Meditation as a tool for stress management has been gaining popularity, but its use as part of a CV rehabilitation program as a complementary therapy has not been well studied, she added.

Dr. Monteiro and colleagues recruited 80 adults with CAD who were undergoing CV rehabilitation to join a meditation program. Of these, 48 accepted (60%) and 40% declined. Those who accepted were part of an exercise-based CV rehabilitation program that met three times a week for at least 6 months. The mean age of the participants was 65 years, and 80% were male.

Participants were randomized to an intervention group with a weekly 90-minute session that included breathing and meditation for 1 month in addition to usual care, or to usual care in the rehabilitation program. Over the next 3 months, the intervention patients were encouraged to practice daily meditation for 20 minutes alone or using video support material, with a weekly follow-up phone call. Assessments of stress, anxiety, and depression took place at baseline and after 4 months using the Perceived Stress Scale, Beck Anxiety Inventory, Beck Depression Inventory, and HeartQoL questionnaire.

At 4 months, individuals in the meditation group had reduced depression levels significantly, by 44%, compared with controls (P < .001). Anxiety and stress decreased significantly, by 30% (P = .04) and 31% (P = .05), respectively. After 4 months, individuals in the control group were offered the opportunity to follow the meditation protocol.

In addition, “the emotional dimension of quality of life increased by 60% in the intervention group,” Dr. Monteiro noted. However, physical QoL did not change between groups.

The study was limited by the small sample size, and more research is needed in larger and more diverse populations, Dr. Monteiro said. However, the results support the value of meditation as an adjunct component of care for CAD patients in a long-term rehabilitation program.
 

Motivation makes a difference

The current study is important as an exploration of “a straightforward, simple, low-risk approach that could be an adjunct to benefit patients with serious cardiovascular disease,” Brian Olshansky, MD, a cardiologist at the University of Iowa, Iowa City, said in an interview.

“We have moved into a time of polypharmacy and multiple interventions for patients with underlying cardiovascular disease which, in many cases, have proven benefit but also potential adverse effects,” he said. “Engaging patients to participate in their health care, when there is serious underlying cardiovascular disease, has potential beneficial impact in many ways. Meditation is a low-risk, low-cost, potentially beneficial adjunct to standard medical therapy that may enhance psychological outcomes as shown here in this small study.”

However, “patients often rely on high-cost, potentially high-risk therapeutic interventions, expecting complete control of their problems without their own collaborative intervention,” he noted.

Dr. Olshansky said he was not surprised by any of the findings, and would have been surprised if meditation had failed to show any benefit for the study population.

“I am very pleased to see these results and would encourage meditation practice to be part of cardiovascular rehabilitation for motivated individuals,” he said. “What did surprise me was the adherence to the meditation protocol for those who participated. This represents a highly motivated group and it may be difficult to expect the same results in less motivated individuals.”

The current study has several strengths, including the use of controls and high rates of adherence to the protocol, said Dr. Olshansky. Other strengths include the standardized approach and the reasonable quality of the outcome measures, which showed a substantial benefit.

However, “this is a small study of motivated individuals of whom 80% were male,” and generalizability to other populations is unclear, Dr. Olshansky said. In addition, the racial mix was not described, and the severity of the underlying coronary artery disease and the therapies provided to these individuals is not detailed. A sicker population may not fare as well.”

The reasons for the benefits of meditation remain uncertain, Dr. Olshansky said. “It could be, specifically, that the meditation itself has physiological effects that ultimately translate into psychosocial benefit. However, those who enrolled and were interested may have derived a placebo effect. In any case, benefit was achieved, but the crossover benefit to the control group is unclear.

“In other words, the statistical approach to benefit is uncertain as to when it was measured, but presumably before the control group was allowed to engage in a meditation practice,” and the follow-up was short term, said Dr. Olshansky.
 

Data support patient engagement

The message to clinicians and patients: “Patients should be engaged in their own health care when it comes to rehabilitation for cardiovascular disease,” said Dr. Olshansky. “Motivated individuals who are educated about a meditative practice performed in a standardized way will have improvement most likely in their quality of life, and when it comes to measurements of depression, stress and anxiety.”

Although the mechanisms behind the benefits remain unclear, “having a standardized credible prescription for which patients can become intimately engaged is beneficial,” he added.

The study received no outside funding. Neither Dr. Monteiro nor Dr. Olshansky had any financial conflicts to disclose.


 

Doctors’ groups are lining up to support new federal legislation to permanently tie Medicare physician payment updates to inflation.

Introduced by four physician U.S. House representatives, HR 2474 would link Medicare fee schedule updates to the Medicare Economic Index, a measure of inflation related to physicians’ practice costs and wages.

That’s a long-sought goal of the American Medical Association, which is leading 120 state medical societies and medical specialty groups in championing the bill.

The legislation is essential to enabling physician practices to better absorb payment distributions triggered by budget neutrality rules, performance adjustments, and periods of high inflation, the groups wrote in a joint letter sent to the bill’s sponsors. The sponsors say they hope the legislation will improve access to care, as low reimbursements cause some physicians to limit their number of Medicare patients.

Physicians groups for years have urged federal lawmakers to scrap short-term fixes staving off Medicare pay cuts in favor of permanent reforms. Unlike nearly all other Medicare clinicians including hospitals, physicians’ Medicare payment updates aren’t currently tied to inflation.

Adjusted for inflation, Medicare payments to physicians have declined 26% between 2001 and 2023, including a 2% payment reduction in 2023, according to the AMA. Small and rural physician practices have been disproportionately affected by these reductions, as have doctors treating low-income or uninsured patients, the AMA said.

Last month, an influential federal advisory panel recommended permanently tying Medicare physician pay increases to inflation. Clinicians’ cost of providing services, measured by the Medicare Economic Index, rose by 2.6% in 2021 and are estimated to have risen 4.7% in 2022, significantly more than in recent years, the Medicare Payment Advisory Commission said.

A version of this article originally appeared on Medscape.com.

Doctors’ groups are lining up to support new federal legislation to permanently tie Medicare physician payment updates to inflation.

Introduced by four physician U.S. House representatives, HR 2474 would link Medicare fee schedule updates to the Medicare Economic Index, a measure of inflation related to physicians’ practice costs and wages.

That’s a long-sought goal of the American Medical Association, which is leading 120 state medical societies and medical specialty groups in championing the bill.

The legislation is essential to enabling physician practices to better absorb payment distributions triggered by budget neutrality rules, performance adjustments, and periods of high inflation, the groups wrote in a joint letter sent to the bill’s sponsors. The sponsors say they hope the legislation will improve access to care, as low reimbursements cause some physicians to limit their number of Medicare patients.

Physicians groups for years have urged federal lawmakers to scrap short-term fixes staving off Medicare pay cuts in favor of permanent reforms. Unlike nearly all other Medicare clinicians including hospitals, physicians’ Medicare payment updates aren’t currently tied to inflation.

Adjusted for inflation, Medicare payments to physicians have declined 26% between 2001 and 2023, including a 2% payment reduction in 2023, according to the AMA. Small and rural physician practices have been disproportionately affected by these reductions, as have doctors treating low-income or uninsured patients, the AMA said.

Last month, an influential federal advisory panel recommended permanently tying Medicare physician pay increases to inflation. Clinicians’ cost of providing services, measured by the Medicare Economic Index, rose by 2.6% in 2021 and are estimated to have risen 4.7% in 2022, significantly more than in recent years, the Medicare Payment Advisory Commission said.

A version of this article originally appeared on Medscape.com.

Doctors’ groups are lining up to support new federal legislation to permanently tie Medicare physician payment updates to inflation.

Introduced by four physician U.S. House representatives, HR 2474 would link Medicare fee schedule updates to the Medicare Economic Index, a measure of inflation related to physicians’ practice costs and wages.

That’s a long-sought goal of the American Medical Association, which is leading 120 state medical societies and medical specialty groups in championing the bill.

The legislation is essential to enabling physician practices to better absorb payment distributions triggered by budget neutrality rules, performance adjustments, and periods of high inflation, the groups wrote in a joint letter sent to the bill’s sponsors. The sponsors say they hope the legislation will improve access to care, as low reimbursements cause some physicians to limit their number of Medicare patients.

Physicians groups for years have urged federal lawmakers to scrap short-term fixes staving off Medicare pay cuts in favor of permanent reforms. Unlike nearly all other Medicare clinicians including hospitals, physicians’ Medicare payment updates aren’t currently tied to inflation.

Adjusted for inflation, Medicare payments to physicians have declined 26% between 2001 and 2023, including a 2% payment reduction in 2023, according to the AMA. Small and rural physician practices have been disproportionately affected by these reductions, as have doctors treating low-income or uninsured patients, the AMA said.

Last month, an influential federal advisory panel recommended permanently tying Medicare physician pay increases to inflation. Clinicians’ cost of providing services, measured by the Medicare Economic Index, rose by 2.6% in 2021 and are estimated to have risen 4.7% in 2022, significantly more than in recent years, the Medicare Payment Advisory Commission said.

A version of this article originally appeared on Medscape.com.