MDedge Psychiatry

Transcranial magnetic stimulation (TMS) is associated with both anxiolytic and antidepressant effects in patients with anxious depression, new research suggests.

In an analysis of data from more than 1,800 patients with a diagnosis of major depressive disorder (MDD), more than 75% also had anxiety. Following TMS, those with anxious depression showed reductions from baseline of at least 50% on anxiety and depression scores.

In addition, the anxious and nonanxious groups had equivalent absolute improvement in scores measuring depression.

“The ultimate message is that TMS is quite effective in the more difficult-to-treat and more disabled group of anxious depressives,” coinvestigator Scott Aaronson, MD, chief science officer, Institute for Advanced Diagnostics and Therapeutics, and director of the Psychedelic Center of Excellence, Sheppard Pratt, Towson, Md., told this news organization.

The findings were published online in the Journal of Clinical Psychiatry.
 

Large cohort

Dr. Aaronson noted that between 50% and 75% of patients with depression also have significant anxiety symptoms.

“The presence of significant anxiety in a depressed person significantly increases depression symptom severity, functional impairment, chronicity, and suicidality,” he said.

In general, “when patients with anxious depression are identified in a treatment study, they are less likely to respond to the index treatment and are frequently excluded from some treatment trials,” he added.

Dr. Aaronson noted that previously reported outcomes from TMS for anxious depression have been “suggestive of efficacy but have not been well studied within a large cohort.” 

To investigate these issues, the current investigators turned to the NeuroStar Advanced Therapy System Clinical Outcomes Registry. It is the largest database of patients with difficult-to-treat depression, all of whom had undergone TMS.

This “extraordinary” database was able to provide previous insight into how often TMS works, whether some of the treatment parameters can be altered while still preserving efficacy, and whether bilateral TMS works better than unilateral TMS in patients with MDD, Dr. Aaronson said.

In the current study, researchers retrospectively analyzed data on 1,820 patients with MDD. All had completed the Patient Health Questinonaire–9 (PHQ-9) and the Generalized Anxiety Disorder–7 (GAD-7) at baseline and following at least one TMS intervention.

Most patients (n = 1,514) had anxious depression, defined as a baseline GAD-7 score of 10 or higher, and 306 had nonanxious depression, defined as a GAD-7 score below that threshold.

The investigators assessed the total sample of these patients who had been treated with any TMS protocol, as well as a subsample of patients (n = 625) who had been treated only with high-frequency left dorsolateral prefrontal cortex (HF-LUL) stimulation.

Patients were also subdivided into intent-to-treat and Completer samples (n = 1,820 and 1,429, respectively).
 

Consistent effects

There was no difference in gender distribution between the anxious and nonanxious group.

However, the anxious group was significantly younger (by about 5 years), compared with the nonanxious group. They also reported higher severity of depressive symptoms at baseline, with PHQ-9 scores approximately 2.5 points higher.

This was a “notable finding, since the PHQ-9 does not contain items directly assessing anxiety,” the researchers wrote.

There were also differences between the groups in the type of TMS protocol they received, with exclusive HF-LUL more common in the nonanxious depression group compared with other types of TMS protocols or unclassified protocols in the anxious depression group.

“Anxiolytic and antidepressant effects were consistent across the [intent-to-treat] and completed samples and patients who received any TMS protocol or only HF-LUL TMS,” the investigators reported.

GAD-7 scores “decreased markedly” in the anxious depression group. GAD-7 response rates ranged from 47.8% to 60.6% and GAD-7 remission rates ranged from 26.4% to 38.0% (P < .0001 for both).

There were no between-group differences in PHQ-9 scores in the magnitude of change pre- to post treatment. The anxious group scored about 2.5 points higher both pre- and post treatment, compared with the anxious group – with an effect size for change ranging from 1.46 to 1.74 in the anxious group and from 1.66 to 1.95 in the nonanxious group.
 

Response, remission rates

Notably, the anxious and nonanxious groups both showed “marked antidepressant effects,” with response and remission rates in the anxious group ranging from 55.2% to 66.8% and from 24.0% to 33.2%, respectively.

However, response and remission rates were significantly higher in the nonanxious versus the anxious group.

“Thus, despite manifesting the same degree of change in the PHQ-9 scores, the higher baseline and post-TMS scores in the anxious group resulted in significantly lower response and remission rates,” the investigators wrote.

They noted that the difference in post-TMS adjusted means was “small” and the groups also “did not differ in the absolute extent of symptoms improvement after multivariate adjustment.”

The relationship changes in the GAD-7 and the PHQ-9 scores “covaried” for the total IT sample (r1818 = 0.69, P < .001), although the relation was more “robust” in the anxious depression group versus the nonanxious depression group (r1512 = .75 vs. r304 = 0.50; P < .001 for both).

“The anxious depressed folks were sicker and had higher scores on scales capturing the severity of their illness,” Dr. Aaronson said. However, their “outcomes were similar, taking into account the higher baseline scores which had the effect of lowering the percent of anxious participants who met response and remission criteria.”

He reported that the average decline in depression rating scale scores was not significantly different between the groups, and the decline in depression scores tracked similarly to the decline in anxiety scores, “meaning they strongly covaried.”

The authors noted that a limitation was that, although the data was prospectively gathered, the analyses were retrospective.
 

Settles the debate?

Commenting on the study, Shan Siddiqi, MD, assistant professor of psychiatry at Harvard Medical School, Boston, said clinicians know that patients with comorbid anxiety are less likely to be referred for TMS, “probably because of the longstanding perception that TMS doesn’t work as well for them.”

courtesy Brigham and Women’s Medical Center

This perception “has persisted, despite several small studies to the contrary, perhaps because we know that these patients are less responsive to other treatments,” said Dr. Siddiqi, who is also director of psychiatric neuromodulation research at Brigham and Women’s Center for Brain Circuit Therapeutics in Boston. He was not involved with the current research.

“This new study will hopefully settle that debate and let us move on to a new question: How do we optimize the treatment for this important patient population that has largely been excluded from many of our prior studies?”  

The NeuroStar Advanced Therapy System Clinical Outcomes Registry, analysis of the registry data, and the drafting of this manuscript were supported by Neuronetics Inc. Dr. Aaronson serves as a scientific adviser to Genomind, LivaNova, Neuronetics, Janssen Pharmaceuticals, and Sage Therapeutics; and has received research support from Compass Pathways and Neuronetics. Dr. Siddiqi is a scientific consultant for Magnus Medical; a clinical consultant for Acacia Mental Health, Kaizen Brain Center, and Boston Precision Neurotherapeutics; and has received investigator-initiated research funding from Neuronetics and BrainsWay. He has also served as a speaker for BrainsWay and PsychU.org, owns stock in BrainsWay and Magnus Medical, and owns intellectual property involving the use of functional connectivity to target TMS.

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

Transcranial magnetic stimulation (TMS) is associated with both anxiolytic and antidepressant effects in patients with anxious depression, new research suggests.

In an analysis of data from more than 1,800 patients with a diagnosis of major depressive disorder (MDD), more than 75% also had anxiety. Following TMS, those with anxious depression showed reductions from baseline of at least 50% on anxiety and depression scores.

In addition, the anxious and nonanxious groups had equivalent absolute improvement in scores measuring depression.

“The ultimate message is that TMS is quite effective in the more difficult-to-treat and more disabled group of anxious depressives,” coinvestigator Scott Aaronson, MD, chief science officer, Institute for Advanced Diagnostics and Therapeutics, and director of the Psychedelic Center of Excellence, Sheppard Pratt, Towson, Md., told this news organization.

The findings were published online in the Journal of Clinical Psychiatry.
 

Large cohort

Dr. Aaronson noted that between 50% and 75% of patients with depression also have significant anxiety symptoms.

“The presence of significant anxiety in a depressed person significantly increases depression symptom severity, functional impairment, chronicity, and suicidality,” he said.

In general, “when patients with anxious depression are identified in a treatment study, they are less likely to respond to the index treatment and are frequently excluded from some treatment trials,” he added.

Dr. Aaronson noted that previously reported outcomes from TMS for anxious depression have been “suggestive of efficacy but have not been well studied within a large cohort.” 

To investigate these issues, the current investigators turned to the NeuroStar Advanced Therapy System Clinical Outcomes Registry. It is the largest database of patients with difficult-to-treat depression, all of whom had undergone TMS.

This “extraordinary” database was able to provide previous insight into how often TMS works, whether some of the treatment parameters can be altered while still preserving efficacy, and whether bilateral TMS works better than unilateral TMS in patients with MDD, Dr. Aaronson said.

In the current study, researchers retrospectively analyzed data on 1,820 patients with MDD. All had completed the Patient Health Questinonaire–9 (PHQ-9) and the Generalized Anxiety Disorder–7 (GAD-7) at baseline and following at least one TMS intervention.

Most patients (n = 1,514) had anxious depression, defined as a baseline GAD-7 score of 10 or higher, and 306 had nonanxious depression, defined as a GAD-7 score below that threshold.

The investigators assessed the total sample of these patients who had been treated with any TMS protocol, as well as a subsample of patients (n = 625) who had been treated only with high-frequency left dorsolateral prefrontal cortex (HF-LUL) stimulation.

Patients were also subdivided into intent-to-treat and Completer samples (n = 1,820 and 1,429, respectively).
 

Consistent effects

There was no difference in gender distribution between the anxious and nonanxious group.

However, the anxious group was significantly younger (by about 5 years), compared with the nonanxious group. They also reported higher severity of depressive symptoms at baseline, with PHQ-9 scores approximately 2.5 points higher.

This was a “notable finding, since the PHQ-9 does not contain items directly assessing anxiety,” the researchers wrote.

There were also differences between the groups in the type of TMS protocol they received, with exclusive HF-LUL more common in the nonanxious depression group compared with other types of TMS protocols or unclassified protocols in the anxious depression group.

“Anxiolytic and antidepressant effects were consistent across the [intent-to-treat] and completed samples and patients who received any TMS protocol or only HF-LUL TMS,” the investigators reported.

GAD-7 scores “decreased markedly” in the anxious depression group. GAD-7 response rates ranged from 47.8% to 60.6% and GAD-7 remission rates ranged from 26.4% to 38.0% (P < .0001 for both).

There were no between-group differences in PHQ-9 scores in the magnitude of change pre- to post treatment. The anxious group scored about 2.5 points higher both pre- and post treatment, compared with the anxious group – with an effect size for change ranging from 1.46 to 1.74 in the anxious group and from 1.66 to 1.95 in the nonanxious group.
 

Response, remission rates

Notably, the anxious and nonanxious groups both showed “marked antidepressant effects,” with response and remission rates in the anxious group ranging from 55.2% to 66.8% and from 24.0% to 33.2%, respectively.

However, response and remission rates were significantly higher in the nonanxious versus the anxious group.

“Thus, despite manifesting the same degree of change in the PHQ-9 scores, the higher baseline and post-TMS scores in the anxious group resulted in significantly lower response and remission rates,” the investigators wrote.

They noted that the difference in post-TMS adjusted means was “small” and the groups also “did not differ in the absolute extent of symptoms improvement after multivariate adjustment.”

The relationship changes in the GAD-7 and the PHQ-9 scores “covaried” for the total IT sample (r1818 = 0.69, P < .001), although the relation was more “robust” in the anxious depression group versus the nonanxious depression group (r1512 = .75 vs. r304 = 0.50; P < .001 for both).

“The anxious depressed folks were sicker and had higher scores on scales capturing the severity of their illness,” Dr. Aaronson said. However, their “outcomes were similar, taking into account the higher baseline scores which had the effect of lowering the percent of anxious participants who met response and remission criteria.”

He reported that the average decline in depression rating scale scores was not significantly different between the groups, and the decline in depression scores tracked similarly to the decline in anxiety scores, “meaning they strongly covaried.”

The authors noted that a limitation was that, although the data was prospectively gathered, the analyses were retrospective.
 

Settles the debate?

Commenting on the study, Shan Siddiqi, MD, assistant professor of psychiatry at Harvard Medical School, Boston, said clinicians know that patients with comorbid anxiety are less likely to be referred for TMS, “probably because of the longstanding perception that TMS doesn’t work as well for them.”

courtesy Brigham and Women’s Medical Center

This perception “has persisted, despite several small studies to the contrary, perhaps because we know that these patients are less responsive to other treatments,” said Dr. Siddiqi, who is also director of psychiatric neuromodulation research at Brigham and Women’s Center for Brain Circuit Therapeutics in Boston. He was not involved with the current research.

“This new study will hopefully settle that debate and let us move on to a new question: How do we optimize the treatment for this important patient population that has largely been excluded from many of our prior studies?”  

The NeuroStar Advanced Therapy System Clinical Outcomes Registry, analysis of the registry data, and the drafting of this manuscript were supported by Neuronetics Inc. Dr. Aaronson serves as a scientific adviser to Genomind, LivaNova, Neuronetics, Janssen Pharmaceuticals, and Sage Therapeutics; and has received research support from Compass Pathways and Neuronetics. Dr. Siddiqi is a scientific consultant for Magnus Medical; a clinical consultant for Acacia Mental Health, Kaizen Brain Center, and Boston Precision Neurotherapeutics; and has received investigator-initiated research funding from Neuronetics and BrainsWay. He has also served as a speaker for BrainsWay and PsychU.org, owns stock in BrainsWay and Magnus Medical, and owns intellectual property involving the use of functional connectivity to target TMS.

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

Transcranial magnetic stimulation (TMS) is associated with both anxiolytic and antidepressant effects in patients with anxious depression, new research suggests.

In an analysis of data from more than 1,800 patients with a diagnosis of major depressive disorder (MDD), more than 75% also had anxiety. Following TMS, those with anxious depression showed reductions from baseline of at least 50% on anxiety and depression scores.

In addition, the anxious and nonanxious groups had equivalent absolute improvement in scores measuring depression.

“The ultimate message is that TMS is quite effective in the more difficult-to-treat and more disabled group of anxious depressives,” coinvestigator Scott Aaronson, MD, chief science officer, Institute for Advanced Diagnostics and Therapeutics, and director of the Psychedelic Center of Excellence, Sheppard Pratt, Towson, Md., told this news organization.

The findings were published online in the Journal of Clinical Psychiatry.
 

Large cohort

Dr. Aaronson noted that between 50% and 75% of patients with depression also have significant anxiety symptoms.

“The presence of significant anxiety in a depressed person significantly increases depression symptom severity, functional impairment, chronicity, and suicidality,” he said.

In general, “when patients with anxious depression are identified in a treatment study, they are less likely to respond to the index treatment and are frequently excluded from some treatment trials,” he added.

Dr. Aaronson noted that previously reported outcomes from TMS for anxious depression have been “suggestive of efficacy but have not been well studied within a large cohort.” 

To investigate these issues, the current investigators turned to the NeuroStar Advanced Therapy System Clinical Outcomes Registry. It is the largest database of patients with difficult-to-treat depression, all of whom had undergone TMS.

This “extraordinary” database was able to provide previous insight into how often TMS works, whether some of the treatment parameters can be altered while still preserving efficacy, and whether bilateral TMS works better than unilateral TMS in patients with MDD, Dr. Aaronson said.

In the current study, researchers retrospectively analyzed data on 1,820 patients with MDD. All had completed the Patient Health Questinonaire–9 (PHQ-9) and the Generalized Anxiety Disorder–7 (GAD-7) at baseline and following at least one TMS intervention.

Most patients (n = 1,514) had anxious depression, defined as a baseline GAD-7 score of 10 or higher, and 306 had nonanxious depression, defined as a GAD-7 score below that threshold.

The investigators assessed the total sample of these patients who had been treated with any TMS protocol, as well as a subsample of patients (n = 625) who had been treated only with high-frequency left dorsolateral prefrontal cortex (HF-LUL) stimulation.

Patients were also subdivided into intent-to-treat and Completer samples (n = 1,820 and 1,429, respectively).
 

Consistent effects

There was no difference in gender distribution between the anxious and nonanxious group.

However, the anxious group was significantly younger (by about 5 years), compared with the nonanxious group. They also reported higher severity of depressive symptoms at baseline, with PHQ-9 scores approximately 2.5 points higher.

This was a “notable finding, since the PHQ-9 does not contain items directly assessing anxiety,” the researchers wrote.

There were also differences between the groups in the type of TMS protocol they received, with exclusive HF-LUL more common in the nonanxious depression group compared with other types of TMS protocols or unclassified protocols in the anxious depression group.

“Anxiolytic and antidepressant effects were consistent across the [intent-to-treat] and completed samples and patients who received any TMS protocol or only HF-LUL TMS,” the investigators reported.

GAD-7 scores “decreased markedly” in the anxious depression group. GAD-7 response rates ranged from 47.8% to 60.6% and GAD-7 remission rates ranged from 26.4% to 38.0% (P < .0001 for both).

There were no between-group differences in PHQ-9 scores in the magnitude of change pre- to post treatment. The anxious group scored about 2.5 points higher both pre- and post treatment, compared with the anxious group – with an effect size for change ranging from 1.46 to 1.74 in the anxious group and from 1.66 to 1.95 in the nonanxious group.
 

Response, remission rates

Notably, the anxious and nonanxious groups both showed “marked antidepressant effects,” with response and remission rates in the anxious group ranging from 55.2% to 66.8% and from 24.0% to 33.2%, respectively.

However, response and remission rates were significantly higher in the nonanxious versus the anxious group.

“Thus, despite manifesting the same degree of change in the PHQ-9 scores, the higher baseline and post-TMS scores in the anxious group resulted in significantly lower response and remission rates,” the investigators wrote.

They noted that the difference in post-TMS adjusted means was “small” and the groups also “did not differ in the absolute extent of symptoms improvement after multivariate adjustment.”

The relationship changes in the GAD-7 and the PHQ-9 scores “covaried” for the total IT sample (r1818 = 0.69, P < .001), although the relation was more “robust” in the anxious depression group versus the nonanxious depression group (r1512 = .75 vs. r304 = 0.50; P < .001 for both).

“The anxious depressed folks were sicker and had higher scores on scales capturing the severity of their illness,” Dr. Aaronson said. However, their “outcomes were similar, taking into account the higher baseline scores which had the effect of lowering the percent of anxious participants who met response and remission criteria.”

He reported that the average decline in depression rating scale scores was not significantly different between the groups, and the decline in depression scores tracked similarly to the decline in anxiety scores, “meaning they strongly covaried.”

The authors noted that a limitation was that, although the data was prospectively gathered, the analyses were retrospective.
 

Settles the debate?

Commenting on the study, Shan Siddiqi, MD, assistant professor of psychiatry at Harvard Medical School, Boston, said clinicians know that patients with comorbid anxiety are less likely to be referred for TMS, “probably because of the longstanding perception that TMS doesn’t work as well for them.”

courtesy Brigham and Women’s Medical Center

This perception “has persisted, despite several small studies to the contrary, perhaps because we know that these patients are less responsive to other treatments,” said Dr. Siddiqi, who is also director of psychiatric neuromodulation research at Brigham and Women’s Center for Brain Circuit Therapeutics in Boston. He was not involved with the current research.

“This new study will hopefully settle that debate and let us move on to a new question: How do we optimize the treatment for this important patient population that has largely been excluded from many of our prior studies?”  

The NeuroStar Advanced Therapy System Clinical Outcomes Registry, analysis of the registry data, and the drafting of this manuscript were supported by Neuronetics Inc. Dr. Aaronson serves as a scientific adviser to Genomind, LivaNova, Neuronetics, Janssen Pharmaceuticals, and Sage Therapeutics; and has received research support from Compass Pathways and Neuronetics. Dr. Siddiqi is a scientific consultant for Magnus Medical; a clinical consultant for Acacia Mental Health, Kaizen Brain Center, and Boston Precision Neurotherapeutics; and has received investigator-initiated research funding from Neuronetics and BrainsWay. He has also served as a speaker for BrainsWay and PsychU.org, owns stock in BrainsWay and Magnus Medical, and owns intellectual property involving the use of functional connectivity to target TMS.

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

Is the ketogenic diet the only way to lose weight? Of course not! Keep track of calories in vs. calories out and almost anyone can lose weight. The problem is keeping it off. To understand that, we need to look at metabolic adaptation and the biology of obesity.

Our bodies have a “set point” that is epigenetically latched onto the environment the brain senses, just as the fetal environment responds to the maternal environment.

Thomas R. Collins/MDedge News

If food is plentiful, our hormones force us to eat until our bodies feel that there are enough fat stores to survive. Because of environmental influences such as highly processed food, preservatives, climate change, and regulation of temperature, our brains have decided that we need more adipose tissue than we did 50-100 years ago. It could be that an element in food has caused a dysfunction of the pathways that regulate our body weight, and most of us “defend” a higher body weight in this environment.

How to counteract that? Not easily. The ketogenic diet works temporarily just like any other diet where calorie intake is lower than usual. It seems to be agreeable to many people because they say they feel full after eating protein, fat, and perhaps some vegetables. Protein and fat are certainly more satiating than simple carbohydrates.

If strictly followed, a ketogenic diet will force the body to burn fat and go into ketosis. Without a source for glucose, the brain will burn ketones from fat stores. Owen and colleagues discovered this in 1969 when they did their now-famous studies of fasting in inpatients at Brigham and Women’s hospital, using IV amino acids to protect muscle mass.
 

Keto for life?

Is the ketogenic diet a healthy diet for the long term? That is a different question.

Of course not – we need high-fiber carbohydrate sources such as whole grains, fruits, and vegetables to keep the colon healthy and obtain the vitamins and minerals needed to make the Krebs cycle, or citric acid cycle, work at its best.

Why, then, are we promoting ketogenic diets for those with obesity and type 2 diabetes? Ketogenic or low-carbohydrate diets are easy to teach and can rapidly help patients lose weight and return their blood glucose, blood pressure, and other metabolic parameters to normal.

The patient will be instructed to avoid all highly processed foods. Studies have shown that highly processed foods, created to maximize flavor, “coerce” people to eat more calories than when presented with the same number of calories in unprocessed foods, a way to fool the brain.
 

Why are we fooling the brain?

We circumvent the natural satiety mechanisms that start with the gut. When we eat, our gastric fundus and intestinal stretch receptors start the process that informs the hypothalamus about food intake. Highly processed foods are usually devoid of fiber and volume, and pack in the calories in small volumes so that the stretch receptors are not activated until more calories are ingested. The study mentioned above developed two ad lib diets with the same number of calories, sugar, fat, and carbohydrate content – one ultraprocessed and the other unprocessed.

That explanation is just the tip of the iceberg, because a lot more than primitive stretch receptors is informing the brain. There are gut hormones that are secreted before and after meals, such as ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (CCK), among a slew of others. These peptide hormones are all secreted from gut cells into the blood or vagus nerve, or both, and alert the brain that there is or is not enough food to maintain body weight at its set point.

It’s a highly regulated and precise system that regulates body weight for survival of the species in this environment. However, the environment has changed over the past 100 years but our genetic makeup for survival of the fittest has not. The mechanism of action for defense of a higher body weight set point in this new environment has not been elucidated as yet. Most likely, there are many players or instigators involved, such as food-supply changes, sedentary lifestyle, ambient temperature, fetal programming, air quality, and global warming and climate change, to name a few.

The goal of obesity researchers is to investigate the underlying mechanisms of the increased prevalence of obesity over the past 100 years. The goal of obesity medicine specialists is to treat obesity in adults and children, and to prevent obesity as much as possible with lifestyle change and medications that have been shown to help “reverse” the metabolic adaptation to this environment. Our newest GLP-1/GIP receptor agonists have been shown in animal models to hit several pathways that lead to obesity. They are not just appetite suppressants. Yes, they do modulate appetite and satiety, but they also affect energy expenditure. The body’s normal reaction to a lack of calorie intake is to reduce resting energy expenditure until body weight increases back to “set point levels.” These agonists prevent that metabolic adaptation. That is why they are true agents that can treat obesity – the disease.

Back to the ketogenic diet. The ketogenic diet can fool the brain temporarily by using protein and fat to elicit satiety with less food intake in calories. After a while, however, gut hormones and other factors begin to counteract the weight loss with a reduction in resting energy and total energy expenditure, and other metabolic measures, to get the body back to a certain body weight set point.

The ketogenic diet also can help dieters avoid ultra- and highly processed foods. In the end, any type of diet that lowers caloric intake will work for weight loss, but it’s the maintenance of that weight loss that makes a long-term difference, and that involves closing the metabolic gap that the body generates to defend fat mass. Understanding this pathophysiology will allow obesity medicine specialists to assist patients with obesity to lose weight and keep it off.

Dr. Apovian is in the department of medicine, division of endocrinology, diabetes, and hypertension, and codirector, Center for Weight Management and Wellness, Harvard Medical School, Boston. She disclosed ties with Altimmune, Cowen and Company, Currax Pharmaceuticals, EPG Communication Holdings, Gelesis Srl, L-Nutra, NeuroBo Pharmaceuticals, National Institutes of Health, Patient-Centered Outcomes Research Institute, GI Dynamics, and Novo Nordisk. A version of this article first appeared on Medscape.com.

Is the ketogenic diet the only way to lose weight? Of course not! Keep track of calories in vs. calories out and almost anyone can lose weight. The problem is keeping it off. To understand that, we need to look at metabolic adaptation and the biology of obesity.

Our bodies have a “set point” that is epigenetically latched onto the environment the brain senses, just as the fetal environment responds to the maternal environment.

Thomas R. Collins/MDedge News

If food is plentiful, our hormones force us to eat until our bodies feel that there are enough fat stores to survive. Because of environmental influences such as highly processed food, preservatives, climate change, and regulation of temperature, our brains have decided that we need more adipose tissue than we did 50-100 years ago. It could be that an element in food has caused a dysfunction of the pathways that regulate our body weight, and most of us “defend” a higher body weight in this environment.

How to counteract that? Not easily. The ketogenic diet works temporarily just like any other diet where calorie intake is lower than usual. It seems to be agreeable to many people because they say they feel full after eating protein, fat, and perhaps some vegetables. Protein and fat are certainly more satiating than simple carbohydrates.

If strictly followed, a ketogenic diet will force the body to burn fat and go into ketosis. Without a source for glucose, the brain will burn ketones from fat stores. Owen and colleagues discovered this in 1969 when they did their now-famous studies of fasting in inpatients at Brigham and Women’s hospital, using IV amino acids to protect muscle mass.
 

Keto for life?

Is the ketogenic diet a healthy diet for the long term? That is a different question.

Of course not – we need high-fiber carbohydrate sources such as whole grains, fruits, and vegetables to keep the colon healthy and obtain the vitamins and minerals needed to make the Krebs cycle, or citric acid cycle, work at its best.

Why, then, are we promoting ketogenic diets for those with obesity and type 2 diabetes? Ketogenic or low-carbohydrate diets are easy to teach and can rapidly help patients lose weight and return their blood glucose, blood pressure, and other metabolic parameters to normal.

The patient will be instructed to avoid all highly processed foods. Studies have shown that highly processed foods, created to maximize flavor, “coerce” people to eat more calories than when presented with the same number of calories in unprocessed foods, a way to fool the brain.
 

Why are we fooling the brain?

We circumvent the natural satiety mechanisms that start with the gut. When we eat, our gastric fundus and intestinal stretch receptors start the process that informs the hypothalamus about food intake. Highly processed foods are usually devoid of fiber and volume, and pack in the calories in small volumes so that the stretch receptors are not activated until more calories are ingested. The study mentioned above developed two ad lib diets with the same number of calories, sugar, fat, and carbohydrate content – one ultraprocessed and the other unprocessed.

That explanation is just the tip of the iceberg, because a lot more than primitive stretch receptors is informing the brain. There are gut hormones that are secreted before and after meals, such as ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (CCK), among a slew of others. These peptide hormones are all secreted from gut cells into the blood or vagus nerve, or both, and alert the brain that there is or is not enough food to maintain body weight at its set point.

It’s a highly regulated and precise system that regulates body weight for survival of the species in this environment. However, the environment has changed over the past 100 years but our genetic makeup for survival of the fittest has not. The mechanism of action for defense of a higher body weight set point in this new environment has not been elucidated as yet. Most likely, there are many players or instigators involved, such as food-supply changes, sedentary lifestyle, ambient temperature, fetal programming, air quality, and global warming and climate change, to name a few.

The goal of obesity researchers is to investigate the underlying mechanisms of the increased prevalence of obesity over the past 100 years. The goal of obesity medicine specialists is to treat obesity in adults and children, and to prevent obesity as much as possible with lifestyle change and medications that have been shown to help “reverse” the metabolic adaptation to this environment. Our newest GLP-1/GIP receptor agonists have been shown in animal models to hit several pathways that lead to obesity. They are not just appetite suppressants. Yes, they do modulate appetite and satiety, but they also affect energy expenditure. The body’s normal reaction to a lack of calorie intake is to reduce resting energy expenditure until body weight increases back to “set point levels.” These agonists prevent that metabolic adaptation. That is why they are true agents that can treat obesity – the disease.

Back to the ketogenic diet. The ketogenic diet can fool the brain temporarily by using protein and fat to elicit satiety with less food intake in calories. After a while, however, gut hormones and other factors begin to counteract the weight loss with a reduction in resting energy and total energy expenditure, and other metabolic measures, to get the body back to a certain body weight set point.

The ketogenic diet also can help dieters avoid ultra- and highly processed foods. In the end, any type of diet that lowers caloric intake will work for weight loss, but it’s the maintenance of that weight loss that makes a long-term difference, and that involves closing the metabolic gap that the body generates to defend fat mass. Understanding this pathophysiology will allow obesity medicine specialists to assist patients with obesity to lose weight and keep it off.

Dr. Apovian is in the department of medicine, division of endocrinology, diabetes, and hypertension, and codirector, Center for Weight Management and Wellness, Harvard Medical School, Boston. She disclosed ties with Altimmune, Cowen and Company, Currax Pharmaceuticals, EPG Communication Holdings, Gelesis Srl, L-Nutra, NeuroBo Pharmaceuticals, National Institutes of Health, Patient-Centered Outcomes Research Institute, GI Dynamics, and Novo Nordisk. A version of this article first appeared on Medscape.com.

Is the ketogenic diet the only way to lose weight? Of course not! Keep track of calories in vs. calories out and almost anyone can lose weight. The problem is keeping it off. To understand that, we need to look at metabolic adaptation and the biology of obesity.

Our bodies have a “set point” that is epigenetically latched onto the environment the brain senses, just as the fetal environment responds to the maternal environment.

Thomas R. Collins/MDedge News

If food is plentiful, our hormones force us to eat until our bodies feel that there are enough fat stores to survive. Because of environmental influences such as highly processed food, preservatives, climate change, and regulation of temperature, our brains have decided that we need more adipose tissue than we did 50-100 years ago. It could be that an element in food has caused a dysfunction of the pathways that regulate our body weight, and most of us “defend” a higher body weight in this environment.

How to counteract that? Not easily. The ketogenic diet works temporarily just like any other diet where calorie intake is lower than usual. It seems to be agreeable to many people because they say they feel full after eating protein, fat, and perhaps some vegetables. Protein and fat are certainly more satiating than simple carbohydrates.

If strictly followed, a ketogenic diet will force the body to burn fat and go into ketosis. Without a source for glucose, the brain will burn ketones from fat stores. Owen and colleagues discovered this in 1969 when they did their now-famous studies of fasting in inpatients at Brigham and Women’s hospital, using IV amino acids to protect muscle mass.
 

Keto for life?

Is the ketogenic diet a healthy diet for the long term? That is a different question.

Of course not – we need high-fiber carbohydrate sources such as whole grains, fruits, and vegetables to keep the colon healthy and obtain the vitamins and minerals needed to make the Krebs cycle, or citric acid cycle, work at its best.

Why, then, are we promoting ketogenic diets for those with obesity and type 2 diabetes? Ketogenic or low-carbohydrate diets are easy to teach and can rapidly help patients lose weight and return their blood glucose, blood pressure, and other metabolic parameters to normal.

The patient will be instructed to avoid all highly processed foods. Studies have shown that highly processed foods, created to maximize flavor, “coerce” people to eat more calories than when presented with the same number of calories in unprocessed foods, a way to fool the brain.
 

Why are we fooling the brain?

We circumvent the natural satiety mechanisms that start with the gut. When we eat, our gastric fundus and intestinal stretch receptors start the process that informs the hypothalamus about food intake. Highly processed foods are usually devoid of fiber and volume, and pack in the calories in small volumes so that the stretch receptors are not activated until more calories are ingested. The study mentioned above developed two ad lib diets with the same number of calories, sugar, fat, and carbohydrate content – one ultraprocessed and the other unprocessed.

That explanation is just the tip of the iceberg, because a lot more than primitive stretch receptors is informing the brain. There are gut hormones that are secreted before and after meals, such as ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (CCK), among a slew of others. These peptide hormones are all secreted from gut cells into the blood or vagus nerve, or both, and alert the brain that there is or is not enough food to maintain body weight at its set point.

It’s a highly regulated and precise system that regulates body weight for survival of the species in this environment. However, the environment has changed over the past 100 years but our genetic makeup for survival of the fittest has not. The mechanism of action for defense of a higher body weight set point in this new environment has not been elucidated as yet. Most likely, there are many players or instigators involved, such as food-supply changes, sedentary lifestyle, ambient temperature, fetal programming, air quality, and global warming and climate change, to name a few.

The goal of obesity researchers is to investigate the underlying mechanisms of the increased prevalence of obesity over the past 100 years. The goal of obesity medicine specialists is to treat obesity in adults and children, and to prevent obesity as much as possible with lifestyle change and medications that have been shown to help “reverse” the metabolic adaptation to this environment. Our newest GLP-1/GIP receptor agonists have been shown in animal models to hit several pathways that lead to obesity. They are not just appetite suppressants. Yes, they do modulate appetite and satiety, but they also affect energy expenditure. The body’s normal reaction to a lack of calorie intake is to reduce resting energy expenditure until body weight increases back to “set point levels.” These agonists prevent that metabolic adaptation. That is why they are true agents that can treat obesity – the disease.

Back to the ketogenic diet. The ketogenic diet can fool the brain temporarily by using protein and fat to elicit satiety with less food intake in calories. After a while, however, gut hormones and other factors begin to counteract the weight loss with a reduction in resting energy and total energy expenditure, and other metabolic measures, to get the body back to a certain body weight set point.

The ketogenic diet also can help dieters avoid ultra- and highly processed foods. In the end, any type of diet that lowers caloric intake will work for weight loss, but it’s the maintenance of that weight loss that makes a long-term difference, and that involves closing the metabolic gap that the body generates to defend fat mass. Understanding this pathophysiology will allow obesity medicine specialists to assist patients with obesity to lose weight and keep it off.

Dr. Apovian is in the department of medicine, division of endocrinology, diabetes, and hypertension, and codirector, Center for Weight Management and Wellness, Harvard Medical School, Boston. She disclosed ties with Altimmune, Cowen and Company, Currax Pharmaceuticals, EPG Communication Holdings, Gelesis Srl, L-Nutra, NeuroBo Pharmaceuticals, National Institutes of Health, Patient-Centered Outcomes Research Institute, GI Dynamics, and Novo Nordisk. A version of this article first appeared on Medscape.com.

Since before the COVID-19 pandemic, primary care providers (PCPs) have been addressing an increasing frequency of mental health concerns, particularly anxiety and stress-related diagnoses, based on a recent study.

These findings point to a sizable gap in psychiatric care that has likely been exacerbated by the pandemic, reported lead author Lisa S. Rotenstein, MD, MBA, assistant professor of medicine at Harvard Medical School and Medical Director of Population Health at Brigham and Women’s Hospital, both in Boston, and colleagues.

To ensure that PCPs can effectively manage this burden, innovative approaches are needed, such as value-based care models, billing codes for integrated behavioral health, and e-consultations with psychiatric colleagues, they added.

“Previous studies demonstrated that the rate of adult mental health outpatient visits increased between 1995 and 2010,” Dr. Rotenstein and colleagues wrote in Health Affairs. “However, more than a decade later, the extent to which the rate of primary care visits addressing mental health concerns has changed is unclear, with multiple health care delivery trends potentially influencing a further increase in prevalence.”

To address this knowledge gap, the investigators turned to the 2006-2018 National Ambulatory Medical Care Surveys, a nationally representative, serial, cross-sectional dataset. The present analysis included 109,898 visits representing 3,891,233,060 weighted visits.

Over the study period, the proportion of PCP visits that addressed mental health concerns rose from 10.7% to 15.9%.

This latter figure has probably increased since the onset of the pandemic, the investigators wrote, while availability of psychiatric care hasn’t kept pace, meaning PCPs are increasingly on the hook for managing mental illness.

“Even before the pandemic, one in five Americans lived with a mental health condition,” Dr. Rotenstein said in a written comment. “The COVID pandemic has only accelerated demand for mental health treatment. ... We know that there aren’t enough psychiatrists to meet this demand.”

Over the course of the study period, the rate of depression and affective disorders diagnoses slowed while anxiety and stress-related disorders were increasingly diagnosed.

“Particularly given the common co-occurrence of anxiety and depression, the trends we identified may represent physicians’ greater comfort over time with accurately diagnosing anxiety in the primary care setting, potentially for diagnoses that previously would have been classified as depression,” the investigators wrote, noting these findings align with a 2014 study by Olfson and colleagues.

Multiple factors associated with primary care mental health visits

Several variables were associated with significantly greater likelihood that a mental health concern would be addressed at a given visit, including female sex, younger age, payment via Medicare or Medicaid, and the physician being the patient’s regular physician.

“Our study demonstrated that mental health concerns were significantly more likely to be addressed in a visit with one’s usual primary care physician,” Dr. Rotenstein said. “This finding emphasizes the value of the longitudinal, supportive relationship developed in primary care for raising and addressing the full continuum of a patient’s needs, including mental health concerns.”

The investigators also observed significant associations between race/ethnicity and likelihood of addressing a mental health concern.

Compared with White patients, Black patients were 40% less likely to have a primary care visit with a mental health concern (odds ratio, 0.6; P less than .001). Similarly, Hispanic patients were 40% less likely than non-Hispanic patients to have a visit with a mental health concern (OR, 0.6; P less than .001).

“Unfortunately, our data don’t give us insight into why Black and Hispanic patients were less likely to have a mental health concern addressed in the context of a primary care visit,” Dr. Rotenstein said. “However, the data do suggest an urgent need to better understand and subsequently address the underlying causes of these disparities.”

She suggested several possible explanations, including differences in rates of screening, issues with access to care, insurance coverage disparities, and communication or cultural barriers.

Stuck in the reimbursement trap

Michael Klinkman, MD , professor of family medicine and learning health sciences at the University of Michigan Medical School, Ann Arbor, said the data align with his own clinical experience.

“The proportion of visits where depression was addresed went down, but the baseline is going up, so I don’t think we’re dealing with any less depression,” Dr. Klinkman said in an interview. “It’s just that there’s a lot more anxiety and stress that we’re finding and dealing with in primary care.”

While most family doctors are comfortable with best practices in managing these conditions, they may feel increasingly overburdened by the sheer number of patients with mental illness under their care alone, according to Dr. Klinkman.

“Primary care docs are increasingly feeling like they’re on their own in dealing with mental health problems,” he said.

While he agreed in theory with the interventions proposed by Dr. Rotenstein and colleagues, some solutions, like billing code changes, may ultimately worsen the burden on primary care providers.

“My fear in all of this, frankly, is that we’re going to create a better sense of the need for primary care practice in general to address mental health and social care issues, and we’re just going to create a lot more work and more widget-counting around doing that,” said Dr. Klinkman. 

Value-based care appears to be a better solution, he said, since “we’re trying to take care of a human being, not the 1,050 pieces of that human being’s care that we’re trying to bundle up with different codes.”

A flat-fee, per-patient model, however, is unlikely to gain traction in the United States.

Dr. Klinkman has been involved in health care system reform up to the federal level, where he has encountered politicians who understood the issues but were incapable of helping because of partisan gridlock, he said. “It’s just politically near impossible to make changes in this basic health care business model.”

Policymakers advised Dr. Klinkman and his colleagues to strive for incremental changes, leaving them to grapple with increasingly complex reimbursement rules.

“We’re kind of stuck in this trap of trying to create new codes for services that we think ought to be better reimbursed,” Dr. Klinkman said. “We’re missing the person in all of this – the human being we’re trying to serve.”

The investigators, Dr. Cain, and Dr. Klinkman disclosed no conflicts of interest.

*This article was updated on 2/27/2023.

Since before the COVID-19 pandemic, primary care providers (PCPs) have been addressing an increasing frequency of mental health concerns, particularly anxiety and stress-related diagnoses, based on a recent study.

These findings point to a sizable gap in psychiatric care that has likely been exacerbated by the pandemic, reported lead author Lisa S. Rotenstein, MD, MBA, assistant professor of medicine at Harvard Medical School and Medical Director of Population Health at Brigham and Women’s Hospital, both in Boston, and colleagues.

To ensure that PCPs can effectively manage this burden, innovative approaches are needed, such as value-based care models, billing codes for integrated behavioral health, and e-consultations with psychiatric colleagues, they added.

“Previous studies demonstrated that the rate of adult mental health outpatient visits increased between 1995 and 2010,” Dr. Rotenstein and colleagues wrote in Health Affairs. “However, more than a decade later, the extent to which the rate of primary care visits addressing mental health concerns has changed is unclear, with multiple health care delivery trends potentially influencing a further increase in prevalence.”

To address this knowledge gap, the investigators turned to the 2006-2018 National Ambulatory Medical Care Surveys, a nationally representative, serial, cross-sectional dataset. The present analysis included 109,898 visits representing 3,891,233,060 weighted visits.

Over the study period, the proportion of PCP visits that addressed mental health concerns rose from 10.7% to 15.9%.

This latter figure has probably increased since the onset of the pandemic, the investigators wrote, while availability of psychiatric care hasn’t kept pace, meaning PCPs are increasingly on the hook for managing mental illness.

“Even before the pandemic, one in five Americans lived with a mental health condition,” Dr. Rotenstein said in a written comment. “The COVID pandemic has only accelerated demand for mental health treatment. ... We know that there aren’t enough psychiatrists to meet this demand.”

Over the course of the study period, the rate of depression and affective disorders diagnoses slowed while anxiety and stress-related disorders were increasingly diagnosed.

“Particularly given the common co-occurrence of anxiety and depression, the trends we identified may represent physicians’ greater comfort over time with accurately diagnosing anxiety in the primary care setting, potentially for diagnoses that previously would have been classified as depression,” the investigators wrote, noting these findings align with a 2014 study by Olfson and colleagues.

Multiple factors associated with primary care mental health visits

Several variables were associated with significantly greater likelihood that a mental health concern would be addressed at a given visit, including female sex, younger age, payment via Medicare or Medicaid, and the physician being the patient’s regular physician.

“Our study demonstrated that mental health concerns were significantly more likely to be addressed in a visit with one’s usual primary care physician,” Dr. Rotenstein said. “This finding emphasizes the value of the longitudinal, supportive relationship developed in primary care for raising and addressing the full continuum of a patient’s needs, including mental health concerns.”

The investigators also observed significant associations between race/ethnicity and likelihood of addressing a mental health concern.

Compared with White patients, Black patients were 40% less likely to have a primary care visit with a mental health concern (odds ratio, 0.6; P less than .001). Similarly, Hispanic patients were 40% less likely than non-Hispanic patients to have a visit with a mental health concern (OR, 0.6; P less than .001).

“Unfortunately, our data don’t give us insight into why Black and Hispanic patients were less likely to have a mental health concern addressed in the context of a primary care visit,” Dr. Rotenstein said. “However, the data do suggest an urgent need to better understand and subsequently address the underlying causes of these disparities.”

She suggested several possible explanations, including differences in rates of screening, issues with access to care, insurance coverage disparities, and communication or cultural barriers.

Stuck in the reimbursement trap

Michael Klinkman, MD , professor of family medicine and learning health sciences at the University of Michigan Medical School, Ann Arbor, said the data align with his own clinical experience.

“The proportion of visits where depression was addresed went down, but the baseline is going up, so I don’t think we’re dealing with any less depression,” Dr. Klinkman said in an interview. “It’s just that there’s a lot more anxiety and stress that we’re finding and dealing with in primary care.”

While most family doctors are comfortable with best practices in managing these conditions, they may feel increasingly overburdened by the sheer number of patients with mental illness under their care alone, according to Dr. Klinkman.

“Primary care docs are increasingly feeling like they’re on their own in dealing with mental health problems,” he said.

While he agreed in theory with the interventions proposed by Dr. Rotenstein and colleagues, some solutions, like billing code changes, may ultimately worsen the burden on primary care providers.

“My fear in all of this, frankly, is that we’re going to create a better sense of the need for primary care practice in general to address mental health and social care issues, and we’re just going to create a lot more work and more widget-counting around doing that,” said Dr. Klinkman. 

Value-based care appears to be a better solution, he said, since “we’re trying to take care of a human being, not the 1,050 pieces of that human being’s care that we’re trying to bundle up with different codes.”

A flat-fee, per-patient model, however, is unlikely to gain traction in the United States.

Dr. Klinkman has been involved in health care system reform up to the federal level, where he has encountered politicians who understood the issues but were incapable of helping because of partisan gridlock, he said. “It’s just politically near impossible to make changes in this basic health care business model.”

Policymakers advised Dr. Klinkman and his colleagues to strive for incremental changes, leaving them to grapple with increasingly complex reimbursement rules.

“We’re kind of stuck in this trap of trying to create new codes for services that we think ought to be better reimbursed,” Dr. Klinkman said. “We’re missing the person in all of this – the human being we’re trying to serve.”

The investigators, Dr. Cain, and Dr. Klinkman disclosed no conflicts of interest.

*This article was updated on 2/27/2023.

Since before the COVID-19 pandemic, primary care providers (PCPs) have been addressing an increasing frequency of mental health concerns, particularly anxiety and stress-related diagnoses, based on a recent study.

These findings point to a sizable gap in psychiatric care that has likely been exacerbated by the pandemic, reported lead author Lisa S. Rotenstein, MD, MBA, assistant professor of medicine at Harvard Medical School and Medical Director of Population Health at Brigham and Women’s Hospital, both in Boston, and colleagues.

To ensure that PCPs can effectively manage this burden, innovative approaches are needed, such as value-based care models, billing codes for integrated behavioral health, and e-consultations with psychiatric colleagues, they added.

“Previous studies demonstrated that the rate of adult mental health outpatient visits increased between 1995 and 2010,” Dr. Rotenstein and colleagues wrote in Health Affairs. “However, more than a decade later, the extent to which the rate of primary care visits addressing mental health concerns has changed is unclear, with multiple health care delivery trends potentially influencing a further increase in prevalence.”

To address this knowledge gap, the investigators turned to the 2006-2018 National Ambulatory Medical Care Surveys, a nationally representative, serial, cross-sectional dataset. The present analysis included 109,898 visits representing 3,891,233,060 weighted visits.

Over the study period, the proportion of PCP visits that addressed mental health concerns rose from 10.7% to 15.9%.

This latter figure has probably increased since the onset of the pandemic, the investigators wrote, while availability of psychiatric care hasn’t kept pace, meaning PCPs are increasingly on the hook for managing mental illness.

“Even before the pandemic, one in five Americans lived with a mental health condition,” Dr. Rotenstein said in a written comment. “The COVID pandemic has only accelerated demand for mental health treatment. ... We know that there aren’t enough psychiatrists to meet this demand.”

Over the course of the study period, the rate of depression and affective disorders diagnoses slowed while anxiety and stress-related disorders were increasingly diagnosed.

“Particularly given the common co-occurrence of anxiety and depression, the trends we identified may represent physicians’ greater comfort over time with accurately diagnosing anxiety in the primary care setting, potentially for diagnoses that previously would have been classified as depression,” the investigators wrote, noting these findings align with a 2014 study by Olfson and colleagues.

Multiple factors associated with primary care mental health visits

Several variables were associated with significantly greater likelihood that a mental health concern would be addressed at a given visit, including female sex, younger age, payment via Medicare or Medicaid, and the physician being the patient’s regular physician.

“Our study demonstrated that mental health concerns were significantly more likely to be addressed in a visit with one’s usual primary care physician,” Dr. Rotenstein said. “This finding emphasizes the value of the longitudinal, supportive relationship developed in primary care for raising and addressing the full continuum of a patient’s needs, including mental health concerns.”

The investigators also observed significant associations between race/ethnicity and likelihood of addressing a mental health concern.

Compared with White patients, Black patients were 40% less likely to have a primary care visit with a mental health concern (odds ratio, 0.6; P less than .001). Similarly, Hispanic patients were 40% less likely than non-Hispanic patients to have a visit with a mental health concern (OR, 0.6; P less than .001).

“Unfortunately, our data don’t give us insight into why Black and Hispanic patients were less likely to have a mental health concern addressed in the context of a primary care visit,” Dr. Rotenstein said. “However, the data do suggest an urgent need to better understand and subsequently address the underlying causes of these disparities.”

She suggested several possible explanations, including differences in rates of screening, issues with access to care, insurance coverage disparities, and communication or cultural barriers.

Stuck in the reimbursement trap

Michael Klinkman, MD , professor of family medicine and learning health sciences at the University of Michigan Medical School, Ann Arbor, said the data align with his own clinical experience.

“The proportion of visits where depression was addresed went down, but the baseline is going up, so I don’t think we’re dealing with any less depression,” Dr. Klinkman said in an interview. “It’s just that there’s a lot more anxiety and stress that we’re finding and dealing with in primary care.”

While most family doctors are comfortable with best practices in managing these conditions, they may feel increasingly overburdened by the sheer number of patients with mental illness under their care alone, according to Dr. Klinkman.

“Primary care docs are increasingly feeling like they’re on their own in dealing with mental health problems,” he said.

While he agreed in theory with the interventions proposed by Dr. Rotenstein and colleagues, some solutions, like billing code changes, may ultimately worsen the burden on primary care providers.

“My fear in all of this, frankly, is that we’re going to create a better sense of the need for primary care practice in general to address mental health and social care issues, and we’re just going to create a lot more work and more widget-counting around doing that,” said Dr. Klinkman. 

Value-based care appears to be a better solution, he said, since “we’re trying to take care of a human being, not the 1,050 pieces of that human being’s care that we’re trying to bundle up with different codes.”

A flat-fee, per-patient model, however, is unlikely to gain traction in the United States.

Dr. Klinkman has been involved in health care system reform up to the federal level, where he has encountered politicians who understood the issues but were incapable of helping because of partisan gridlock, he said. “It’s just politically near impossible to make changes in this basic health care business model.”

Policymakers advised Dr. Klinkman and his colleagues to strive for incremental changes, leaving them to grapple with increasingly complex reimbursement rules.

“We’re kind of stuck in this trap of trying to create new codes for services that we think ought to be better reimbursed,” Dr. Klinkman said. “We’re missing the person in all of this – the human being we’re trying to serve.”

The investigators, Dr. Cain, and Dr. Klinkman disclosed no conflicts of interest.

*This article was updated on 2/27/2023.

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Psychiatric electroceutical interventions (PEIs) – including Food and Drug Administration–approved therapies like electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS), as well as experimental interventions such as deep brain stimulation (DBS) and adaptive brain implants (ABI) – offer therapeutic promise for patients suffering with major depressive disorder (MDD). Yet there remain many open questions regarding their use, even in cases where their safety and effectiveness is well established.

Our research aims to better understand how different stakeholder groups view these interventions. We conducted a series of interviews with psychiatrists, patients with MDD, and members of the public to more fully comprehend these groups’ perceptions of barriers to using these therapies.¹ They raised concerns about limitations to access posed by the limited geographic availability of these treatments, their cost, and lack of insurance coverage. In addition, each stakeholder group cited lack of knowledge about PEIs as a perceived barrier to their wider implementation in depression care.

Michigan State University

Our participants recognized there are significant geographic limitations to accessing PEIs, as many of these treatments are available only in large, well-resourced cities. This is especially true for DBS and ABIs as they remain investigational, require neurosurgery, and currently are offered only during clinical research trials. However, even for established therapies like ECT and rTMS, access often remains limited to larger treatment centers. Further, training on the proper implementation and use of these modalities is limited in the United States. Current requirements from the Accreditation Council for Graduate Medical Education state only that psychiatry residents demonstrate knowledge of these therapies and their indications, falling short of requiring first-hand experience in referring or administering them.²

Michigan State University

Our participants also perceived the cost of these therapies as a significant barrier affecting a large proportion of patients who could potentially benefit from them. Another frequently mentioned barrier is the lack of insurance coverage for existing PEIs, particularly rTMS. Even when insurance covers treatment with an approved PEI (for example, ECT, rTMS), there may be a requirement to have tried and failed multiple antidepressant medications first. These insurance requirements may contribute to a lack of general clarity about when these treatments should be used. The psychiatrists we interviewed, for example, were almost evenly split between believing that ECT and/or rTMS should be offered earlier in the course of therapy and believing that they should be reserved only for patients with treatment-resistant depression.

Michigan State University

Further, some psychiatrists we interviewed stated that they wanted more information about the appropriate use of these treatments. This is unsurprising, as the available guidelines for the approved electroceutical treatments are outdated. Although the American Psychiatric Association Task Force is due to publish updated guidelines for ECT, it has been more than 20 years since the current guidelines were published.³ More recent guidelines, such as those issued in 2016 by the Canadian Network for Mood and Anxiety Treatments cite studies that were even then several years old.⁴ For rTMS, newer guidelines are available, but they have not yet been revised to include recent developments such as the SAINT protocol.^5,6

While useful, clinical guidelines do not provide all of the information psychiatrists require for clinical decision-making. They are only as good as the evidence available and to the extent that they include all of the considerations important to psychiatrists and the specific patients they are treating.^7,8 We asked the psychiatrists in our interviews what practical information they would like to see included in treatment guidelines. They offered a range of suggestions: better guidance about which patients would be most likely to benefit, when to offer the treatments, and how to combine these therapies with other interventions.

Pennsylvania State University

For the experimental PEIs (DBS and ABIs), similar questions and concerns arise. In the current research context, psychiatrists may not be aware of which patients are good candidates for referral to clinical trials. If these therapies are approved, similar questions about patient selection and place in treatment (for example, first line, second line, etc.) remain.⁹

Finally, each of our participant groups believed that patients and the public lack adequate knowledge about electroceutical interventions, and they emphasized the importance of giving potential patients sufficient information to enable them to provide valid informed consent. This is important in the case of the approved electroceutical therapies (ECT and rTMS), in part because of the potential for decision-making to be influenced unduly by misinformation and controversy – especially given that the media’s depiction of these interventions might influence patients’ willingness to receive helpful therapies such as ECT.¹⁰

Our interviews were used to inform the development of a national survey of these four stakeholder groups, which will provide further information about perceived barriers to accessing PEIs.

Dr. Bluhm is associate professor of philosophy at Michigan State University, East Lansing. Dr. Achtyes is director of the division of psychiatry and behavioral medicine at Michigan State University, Grand Rapids. Dr. McCright is chair of the department of sociology at Michigan State University. Dr. Cabrera is Dorothy Foehr Huck and J. Lloyd Huck Chair in Neuroethics at the Huck Institutes of the Life Sciences, Penn State University, University Park.

References

1. Cabrera LY et al. Psychiatry Res. 2022 Jul;313:114612. doi: 10.1016/j.psychres.2022.114612.

2. Accreditation Council for Graduate Medical Education. Psychiatry – Program Requirements and FAQs. https://www.acgme.org/specialties/psychiatry/program-requirements-and-faqs-and-applications/

3. American Psychiatric Association. The Practice of Electroconvulsive Therapy, Second Edition: Recommendations for Treatment, Training, and Privileging. 2001.

4. Miley RV et al. Can J Psychiatry. 2016 Sep;61(9):561-75. doi: 10.1177/0706743716660033.

5. Perera T et al. Brain Stimul. 2016 May-Jun;9(3):336-46. doi: 10.1016/j.brs.2016.03.010.

6. Cole EJ et al. Am J Psychiatry. 2020 Aug 1;177(8):716-26. doi: 10.1176/appi.ajp.2019.19070720.

7. Gabriel FC et al. PLoS One. 2020 Apr 21;15(4):e0231700. doi: 10.1371/journal.pone.0231700.

8. Woolf SH et al. BMJ. 1999 Feb 20;318(7182):527-30. doi: 10.1136/bmj.318.7182.527.

9. Widge AS et al. Biol Psychiatry. 2016 Feb 15;79(4):e9-10. doi: 10.1016/j.biopsych.2015.06.005.

10. Sienaert P. Brain Stimul. 2016 Nov-Dec;9(6):882-91. doi: 10.1016/j.brs.2016.07.005.

Psychiatric electroceutical interventions (PEIs) – including Food and Drug Administration–approved therapies like electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS), as well as experimental interventions such as deep brain stimulation (DBS) and adaptive brain implants (ABI) – offer therapeutic promise for patients suffering with major depressive disorder (MDD). Yet there remain many open questions regarding their use, even in cases where their safety and effectiveness is well established.

Our research aims to better understand how different stakeholder groups view these interventions. We conducted a series of interviews with psychiatrists, patients with MDD, and members of the public to more fully comprehend these groups’ perceptions of barriers to using these therapies.¹ They raised concerns about limitations to access posed by the limited geographic availability of these treatments, their cost, and lack of insurance coverage. In addition, each stakeholder group cited lack of knowledge about PEIs as a perceived barrier to their wider implementation in depression care.

Michigan State University

Our participants recognized there are significant geographic limitations to accessing PEIs, as many of these treatments are available only in large, well-resourced cities. This is especially true for DBS and ABIs as they remain investigational, require neurosurgery, and currently are offered only during clinical research trials. However, even for established therapies like ECT and rTMS, access often remains limited to larger treatment centers. Further, training on the proper implementation and use of these modalities is limited in the United States. Current requirements from the Accreditation Council for Graduate Medical Education state only that psychiatry residents demonstrate knowledge of these therapies and their indications, falling short of requiring first-hand experience in referring or administering them.²

Michigan State University

Our participants also perceived the cost of these therapies as a significant barrier affecting a large proportion of patients who could potentially benefit from them. Another frequently mentioned barrier is the lack of insurance coverage for existing PEIs, particularly rTMS. Even when insurance covers treatment with an approved PEI (for example, ECT, rTMS), there may be a requirement to have tried and failed multiple antidepressant medications first. These insurance requirements may contribute to a lack of general clarity about when these treatments should be used. The psychiatrists we interviewed, for example, were almost evenly split between believing that ECT and/or rTMS should be offered earlier in the course of therapy and believing that they should be reserved only for patients with treatment-resistant depression.

Michigan State University

Further, some psychiatrists we interviewed stated that they wanted more information about the appropriate use of these treatments. This is unsurprising, as the available guidelines for the approved electroceutical treatments are outdated. Although the American Psychiatric Association Task Force is due to publish updated guidelines for ECT, it has been more than 20 years since the current guidelines were published.³ More recent guidelines, such as those issued in 2016 by the Canadian Network for Mood and Anxiety Treatments cite studies that were even then several years old.⁴ For rTMS, newer guidelines are available, but they have not yet been revised to include recent developments such as the SAINT protocol.^5,6

While useful, clinical guidelines do not provide all of the information psychiatrists require for clinical decision-making. They are only as good as the evidence available and to the extent that they include all of the considerations important to psychiatrists and the specific patients they are treating.^7,8 We asked the psychiatrists in our interviews what practical information they would like to see included in treatment guidelines. They offered a range of suggestions: better guidance about which patients would be most likely to benefit, when to offer the treatments, and how to combine these therapies with other interventions.

Pennsylvania State University

For the experimental PEIs (DBS and ABIs), similar questions and concerns arise. In the current research context, psychiatrists may not be aware of which patients are good candidates for referral to clinical trials. If these therapies are approved, similar questions about patient selection and place in treatment (for example, first line, second line, etc.) remain.⁹

Finally, each of our participant groups believed that patients and the public lack adequate knowledge about electroceutical interventions, and they emphasized the importance of giving potential patients sufficient information to enable them to provide valid informed consent. This is important in the case of the approved electroceutical therapies (ECT and rTMS), in part because of the potential for decision-making to be influenced unduly by misinformation and controversy – especially given that the media’s depiction of these interventions might influence patients’ willingness to receive helpful therapies such as ECT.¹⁰

Our interviews were used to inform the development of a national survey of these four stakeholder groups, which will provide further information about perceived barriers to accessing PEIs.

Dr. Bluhm is associate professor of philosophy at Michigan State University, East Lansing. Dr. Achtyes is director of the division of psychiatry and behavioral medicine at Michigan State University, Grand Rapids. Dr. McCright is chair of the department of sociology at Michigan State University. Dr. Cabrera is Dorothy Foehr Huck and J. Lloyd Huck Chair in Neuroethics at the Huck Institutes of the Life Sciences, Penn State University, University Park.

References

1. Cabrera LY et al. Psychiatry Res. 2022 Jul;313:114612. doi: 10.1016/j.psychres.2022.114612.

2. Accreditation Council for Graduate Medical Education. Psychiatry – Program Requirements and FAQs. https://www.acgme.org/specialties/psychiatry/program-requirements-and-faqs-and-applications/

3. American Psychiatric Association. The Practice of Electroconvulsive Therapy, Second Edition: Recommendations for Treatment, Training, and Privileging. 2001.

4. Miley RV et al. Can J Psychiatry. 2016 Sep;61(9):561-75. doi: 10.1177/0706743716660033.

5. Perera T et al. Brain Stimul. 2016 May-Jun;9(3):336-46. doi: 10.1016/j.brs.2016.03.010.

6. Cole EJ et al. Am J Psychiatry. 2020 Aug 1;177(8):716-26. doi: 10.1176/appi.ajp.2019.19070720.

7. Gabriel FC et al. PLoS One. 2020 Apr 21;15(4):e0231700. doi: 10.1371/journal.pone.0231700.

8. Woolf SH et al. BMJ. 1999 Feb 20;318(7182):527-30. doi: 10.1136/bmj.318.7182.527.

9. Widge AS et al. Biol Psychiatry. 2016 Feb 15;79(4):e9-10. doi: 10.1016/j.biopsych.2015.06.005.

10. Sienaert P. Brain Stimul. 2016 Nov-Dec;9(6):882-91. doi: 10.1016/j.brs.2016.07.005.

Psychiatric electroceutical interventions (PEIs) – including Food and Drug Administration–approved therapies like electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS), as well as experimental interventions such as deep brain stimulation (DBS) and adaptive brain implants (ABI) – offer therapeutic promise for patients suffering with major depressive disorder (MDD). Yet there remain many open questions regarding their use, even in cases where their safety and effectiveness is well established.

Our research aims to better understand how different stakeholder groups view these interventions. We conducted a series of interviews with psychiatrists, patients with MDD, and members of the public to more fully comprehend these groups’ perceptions of barriers to using these therapies.¹ They raised concerns about limitations to access posed by the limited geographic availability of these treatments, their cost, and lack of insurance coverage. In addition, each stakeholder group cited lack of knowledge about PEIs as a perceived barrier to their wider implementation in depression care.

Michigan State University

Our participants recognized there are significant geographic limitations to accessing PEIs, as many of these treatments are available only in large, well-resourced cities. This is especially true for DBS and ABIs as they remain investigational, require neurosurgery, and currently are offered only during clinical research trials. However, even for established therapies like ECT and rTMS, access often remains limited to larger treatment centers. Further, training on the proper implementation and use of these modalities is limited in the United States. Current requirements from the Accreditation Council for Graduate Medical Education state only that psychiatry residents demonstrate knowledge of these therapies and their indications, falling short of requiring first-hand experience in referring or administering them.²

Michigan State University

Our participants also perceived the cost of these therapies as a significant barrier affecting a large proportion of patients who could potentially benefit from them. Another frequently mentioned barrier is the lack of insurance coverage for existing PEIs, particularly rTMS. Even when insurance covers treatment with an approved PEI (for example, ECT, rTMS), there may be a requirement to have tried and failed multiple antidepressant medications first. These insurance requirements may contribute to a lack of general clarity about when these treatments should be used. The psychiatrists we interviewed, for example, were almost evenly split between believing that ECT and/or rTMS should be offered earlier in the course of therapy and believing that they should be reserved only for patients with treatment-resistant depression.

Michigan State University

Further, some psychiatrists we interviewed stated that they wanted more information about the appropriate use of these treatments. This is unsurprising, as the available guidelines for the approved electroceutical treatments are outdated. Although the American Psychiatric Association Task Force is due to publish updated guidelines for ECT, it has been more than 20 years since the current guidelines were published.³ More recent guidelines, such as those issued in 2016 by the Canadian Network for Mood and Anxiety Treatments cite studies that were even then several years old.⁴ For rTMS, newer guidelines are available, but they have not yet been revised to include recent developments such as the SAINT protocol.^5,6

While useful, clinical guidelines do not provide all of the information psychiatrists require for clinical decision-making. They are only as good as the evidence available and to the extent that they include all of the considerations important to psychiatrists and the specific patients they are treating.^7,8 We asked the psychiatrists in our interviews what practical information they would like to see included in treatment guidelines. They offered a range of suggestions: better guidance about which patients would be most likely to benefit, when to offer the treatments, and how to combine these therapies with other interventions.

Pennsylvania State University

For the experimental PEIs (DBS and ABIs), similar questions and concerns arise. In the current research context, psychiatrists may not be aware of which patients are good candidates for referral to clinical trials. If these therapies are approved, similar questions about patient selection and place in treatment (for example, first line, second line, etc.) remain.⁹

Finally, each of our participant groups believed that patients and the public lack adequate knowledge about electroceutical interventions, and they emphasized the importance of giving potential patients sufficient information to enable them to provide valid informed consent. This is important in the case of the approved electroceutical therapies (ECT and rTMS), in part because of the potential for decision-making to be influenced unduly by misinformation and controversy – especially given that the media’s depiction of these interventions might influence patients’ willingness to receive helpful therapies such as ECT.¹⁰

Our interviews were used to inform the development of a national survey of these four stakeholder groups, which will provide further information about perceived barriers to accessing PEIs.

Dr. Bluhm is associate professor of philosophy at Michigan State University, East Lansing. Dr. Achtyes is director of the division of psychiatry and behavioral medicine at Michigan State University, Grand Rapids. Dr. McCright is chair of the department of sociology at Michigan State University. Dr. Cabrera is Dorothy Foehr Huck and J. Lloyd Huck Chair in Neuroethics at the Huck Institutes of the Life Sciences, Penn State University, University Park.

References

1. Cabrera LY et al. Psychiatry Res. 2022 Jul;313:114612. doi: 10.1016/j.psychres.2022.114612.

2. Accreditation Council for Graduate Medical Education. Psychiatry – Program Requirements and FAQs. https://www.acgme.org/specialties/psychiatry/program-requirements-and-faqs-and-applications/

3. American Psychiatric Association. The Practice of Electroconvulsive Therapy, Second Edition: Recommendations for Treatment, Training, and Privileging. 2001.

4. Miley RV et al. Can J Psychiatry. 2016 Sep;61(9):561-75. doi: 10.1177/0706743716660033.

5. Perera T et al. Brain Stimul. 2016 May-Jun;9(3):336-46. doi: 10.1016/j.brs.2016.03.010.

6. Cole EJ et al. Am J Psychiatry. 2020 Aug 1;177(8):716-26. doi: 10.1176/appi.ajp.2019.19070720.

7. Gabriel FC et al. PLoS One. 2020 Apr 21;15(4):e0231700. doi: 10.1371/journal.pone.0231700.

8. Woolf SH et al. BMJ. 1999 Feb 20;318(7182):527-30. doi: 10.1136/bmj.318.7182.527.

9. Widge AS et al. Biol Psychiatry. 2016 Feb 15;79(4):e9-10. doi: 10.1016/j.biopsych.2015.06.005.

10. Sienaert P. Brain Stimul. 2016 Nov-Dec;9(6):882-91. doi: 10.1016/j.brs.2016.07.005.

Elevated depressive symptoms were associated with an additional brain age of nearly 3 years, based on data from more than 600 individuals.

Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.

Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.

The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.

In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).

The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.

Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.

The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.

However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.

In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.

The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.

Elevated depressive symptoms were associated with an additional brain age of nearly 3 years, based on data from more than 600 individuals.

Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.

Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.

The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.

In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).

The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.

Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.

The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.

However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.

In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.

The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.

Elevated depressive symptoms were associated with an additional brain age of nearly 3 years, based on data from more than 600 individuals.

Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.

Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.

The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.

In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).

The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.

Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.

The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.

However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.

In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.

The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.

Sleep disturbances are consistently high throughout the course of psychosis, with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.

For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles – or bursts of brainwave activity during sleep identified by electroencephalography.

“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, told this news organization.

University of Pittsburgh

‘Window of opportunity’

Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).

Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.

Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5,135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1,575 patients and 977 healthy controls.

The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.

The pooled prevalence of sleep disturbances was 50% across clinical stages (95% confidence interval, 40%-61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.

The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases, 48% of the EP group, and 27% of the CP group.

“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Dr. Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”

He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.

“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Dr. Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
 

Altered sleep architecture

To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.

There was a significant standardized mean difference in pooled cases versus controls (SMD, 1.0; 95% CI, 0.7-1.3; P < .001). Each clinical group showed poorer sleep quality, compared with controls.

When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.

Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.

Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.

The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.

They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
 

‘Robust’ spindle results

As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, –1.06), spindle amplitude (SMD, –1.08), and spindle duration (SMD, −1.21), compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.

Dr. Ferrarelli noted the results for spindle abnormalities were among “the most robust” and show that these abnormalities “tend to get worse over the course of the illness.”

The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Dr. Ferrarelli.

“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.

He noted that spindles may also represent a promising target for treatment interventions and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.

Another way to evoke target-brain activity may be through auditory tones – with a patient listening to a particular sound through headphones while asleep, Dr. Ferrarelli said.
 

Reaffirms previous data

Commenting on the study, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”

That so many at-risk study subjects had a sleep abnormality is not surprising, said Dr. Lieberman, who was not involved with the current research.

“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: How distinctive is this from what occurs in people who don’t develop the illness?”

The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Dr. Lieberman.

“But it’s not clear from these results how one would do that,” he added.

The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.

The study was supported by the National Institute of Mental Health. Dr. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Dr. Lieberman has reported no relevant financial relationships.

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

Sleep disturbances are consistently high throughout the course of psychosis, with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.

For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles – or bursts of brainwave activity during sleep identified by electroencephalography.

“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, told this news organization.

University of Pittsburgh

‘Window of opportunity’

Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).

Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.

Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5,135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1,575 patients and 977 healthy controls.

The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.

The pooled prevalence of sleep disturbances was 50% across clinical stages (95% confidence interval, 40%-61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.

The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases, 48% of the EP group, and 27% of the CP group.

“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Dr. Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”

He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.

“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Dr. Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
 

Altered sleep architecture

To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.

There was a significant standardized mean difference in pooled cases versus controls (SMD, 1.0; 95% CI, 0.7-1.3; P < .001). Each clinical group showed poorer sleep quality, compared with controls.

When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.

Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.

Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.

The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.

They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
 

‘Robust’ spindle results

As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, –1.06), spindle amplitude (SMD, –1.08), and spindle duration (SMD, −1.21), compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.

Dr. Ferrarelli noted the results for spindle abnormalities were among “the most robust” and show that these abnormalities “tend to get worse over the course of the illness.”

The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Dr. Ferrarelli.

“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.

He noted that spindles may also represent a promising target for treatment interventions and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.

Another way to evoke target-brain activity may be through auditory tones – with a patient listening to a particular sound through headphones while asleep, Dr. Ferrarelli said.
 

Reaffirms previous data

Commenting on the study, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”

That so many at-risk study subjects had a sleep abnormality is not surprising, said Dr. Lieberman, who was not involved with the current research.

“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: How distinctive is this from what occurs in people who don’t develop the illness?”

The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Dr. Lieberman.

“But it’s not clear from these results how one would do that,” he added.

The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.

The study was supported by the National Institute of Mental Health. Dr. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Dr. Lieberman has reported no relevant financial relationships.

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

Sleep disturbances are consistently high throughout the course of psychosis, with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.

For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles – or bursts of brainwave activity during sleep identified by electroencephalography.

“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, told this news organization.

University of Pittsburgh

‘Window of opportunity’

Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).

Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.

Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5,135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1,575 patients and 977 healthy controls.

The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.

The pooled prevalence of sleep disturbances was 50% across clinical stages (95% confidence interval, 40%-61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.

The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases, 48% of the EP group, and 27% of the CP group.

“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Dr. Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”

He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.

“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Dr. Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
 

Altered sleep architecture

To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.

There was a significant standardized mean difference in pooled cases versus controls (SMD, 1.0; 95% CI, 0.7-1.3; P < .001). Each clinical group showed poorer sleep quality, compared with controls.

When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.

Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.

Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.

The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.

They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
 

‘Robust’ spindle results

As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, –1.06), spindle amplitude (SMD, –1.08), and spindle duration (SMD, −1.21), compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.

Dr. Ferrarelli noted the results for spindle abnormalities were among “the most robust” and show that these abnormalities “tend to get worse over the course of the illness.”

The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Dr. Ferrarelli.

“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.

He noted that spindles may also represent a promising target for treatment interventions and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.

Another way to evoke target-brain activity may be through auditory tones – with a patient listening to a particular sound through headphones while asleep, Dr. Ferrarelli said.
 

Reaffirms previous data

Commenting on the study, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”

That so many at-risk study subjects had a sleep abnormality is not surprising, said Dr. Lieberman, who was not involved with the current research.

“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: How distinctive is this from what occurs in people who don’t develop the illness?”

The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Dr. Lieberman.

“But it’s not clear from these results how one would do that,” he added.

The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.

The study was supported by the National Institute of Mental Health. Dr. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Dr. Lieberman has reported no relevant financial relationships.

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

As physicians well know, magic wands don’t exist. If they did, every patient would recover in the exam room, prior authorization wouldn’t exist, and continuing medical education credits would be printed on bearer bonds.

But in the spirit of suspended disbelief, we asked physicians and other contributors what their three wishes would be for their patients, practice/hospital, and health systems. Because, hey – we all need to dream.
 

Suzanne C. Boulter, MD, adjunct professor of pediatrics and community and family medicine, Geisel School of Medicine at Dartmouth, Hanover, N.H.
Patients: An end to gun violence.
Practice/hospital: Adequate staffing and pediatric bed availability.
Health system: Universal access to health insurance.

Sarah G. Candler, MD, MPH, care team medical director and director of academic relations, Iora Primary Care, Northside Clinic, Houston
Patients: Systems of health that start with communities of safety, including access to affordable housing, food, transportation, and health care.
Practice/hospital: I.N.T.E.R.O.P.E.R.A.B.I.L.I.T.Y.
Health system: Clinician leadership that has the power (often aka funding) to do what’s right, not just what’s right in front of us.

Arthur L. Caplan, PhD, bioethicist, New York University Langone Health
Patients: I wish for patients in the United States greater access to affordable primary care. There are still too many people without insurance or a reasonably accessible quality provider. And I especially wish for the rapid expansion of affordable training programs to meet staffing needs, including more scholarships, 3-year programs, and more new primary care–oriented schools.
Hospital: Increased staffing, especially nursing. There are too many retirements, too much burnout, and too much privatization into boutique practices to ensure the ability to provide high-quality, safe, patient-oriented care.
Health system: I wish for health systems to seriously move into electronic medicine. While billing has become electronic, there is still much to be done to supplement diagnosis, training, and standardized data collection on key metrics. Systems are not yet behaving in a manner consistent with the hype in this regard.

Stephen Devries, MD, executive director, Gaples Institute (nonprofit) and adjunct associate professor of nutrition, Harvard School of Public Health, Boston
Patients: Patients continue to demand more from their health care professionals and insist that they are offered evidence-based counseling on nutrition and lifestyle strategies.
Practice: Quality-based reimbursement for medical services will take hold that will incentivize much-needed preventive care.
Hospital: Hospitals will more fully embrace the role of serving as true centers of health and focus as much on preventive medicine as on the more lucrative areas of high-tech treatment.

Peter D. Friedmann, MD, MPH, chief research officer, Baystate Health, Springfield, Mass.
Seconded by: Elisabeth Poorman, MD, general internist, University of Washington Clinic, Kent
Patients: Don’t forget the ongoing epidemic of substance use disorder, a major cause of premature mortality. Descheduling of cannabis and expungement of cannabis-related convictions.
Practice/hospital: Commitment of hospitals and practices to address stigma and ensure delivery of medications for opioid use disorder in primary care, the emergency department, and inpatient settings.
Health system: Reform of antiquated methadone regulations to permit office-based prescription and pharmacy dispensing to treat opioid use disorder, as is the case in most of the world.

Robert Glatter, MD, emergency physician, New York
Patients: I want all patients to understand the enormous strain the health care system has been under – not just with the pandemic, the tripledemic, and mpox [previously called monkeypox], but well before the onset of these public health crises.
Hospital: The medical profession has endured not only burnout but a growing mental health crisis, staffing shortages, a physician addiction crisis, and increased attrition in the decade leading up to the pandemic. The pandemic was like a punch in the gut, occurring at the most inopportune time one could imagine.
Health system: The intersection of health and the state of our public health deserves important mention. Unless we take action to bolster our public health infrastructure, our health care system will be in jeopardy, unable to handle the next pandemic, which could be just around the corner.

William E. Golden, MD, medical director of Arkansas Medicaid, professor of medicine and public health, University of Arkansas for Medical Sciences, Little Rock
Patients: Affordable options for diabetes and obesity management.
Health system: Greater investment by health systems and third-party payers in primary care infrastructure.

Gregory A. Hood, MD, Baptist Health, Lexington, Ky.
Patients: To embrace the gift of getting out in the world, being active, and connecting with others – having put down the screens.
Health system: To be freed from the financial gamesmanship of the insurers as they continue to serve their goals of promoting their hedge fund investing over meaningful and productive partnering with primary care physicians, and that they gain insight that they are one of the main reasons they can’t find PCPs to connect with to render care in disadvantaged environments – because they made it economically impossible to do so.

Robert H. Hopkins Jr., MD, associate professor of internal medicine and pediatrics and director of the division of general internal medicine, University of Arkansas for Medical Sciences, Little Rock
Patients/Health system: I would wish for staged implementation of universal basic health coverage for all, perhaps closest to the French or Canadian model. This would need to be coupled with expanded funding for nursing education, graduate medical education, and tracing of other health-related professionals.

Harvey Hsu, MD, Banner Health, Phoenix
Patients: More clear guidelines that are simple to understand. This can apply to colonoscopy (now age 45), immunizations, blood pressure goals. I wish medications were not as expensive so patients can take the best medicine for them and not stop taking them when they hit their donut hole in coverage.
Practice: We have been functioning on a leaner basis to cut down costs. When the pandemic hit, turnover was high and we lost PAs, nurses, front-office staff, and physicians. Having adequate staffing is probably number one on many lists. One way we dealt with lack of staffing was converting in-person visits to telehealth. Video visits are paid the same as in-person visits, but if the patient could not get their video to work, then it would be a telephone visit. Now many insurances do not even pay for telephone visits. So I would wish that we could still be reimbursed for telehealth visits.
Health system: I would wish for our health system to recognize the extra work required to take care of patients while improving quality and meeting quality measures. Allowing more time for patient visits could be one way to meet those goals or having more support staff to make sure patients get their colonoscopy/mammograms done, improve their sugars, and take their medications.

Jan L. Shifren, MD, Vincent Trustees Professor, obstetrics, gynecology, and reproductive biology, Harvard Medical School, and director of the Midlife Women’s Health Center at Massachusetts General Hospital, Boston
Patients: I wish for patients to be actively involved in all aspects of their care, well informed with shared decision-making.
Practice: I wish for the enormous time demands of electronic medical records and documentation to not distract from the pleasure of caring for patients.
Health system: Patient care remains at the center of decisions and programs.

Timothy J. Joos, MD, MPH, internal medicine/pediatrics, Seattle
Health system: I wish someone could figure out how we could be reimbursed for the quality of care we provide instead of the volume of patients we see. I wish EMRs could become less complicated and more user-friendly rather than needing advanced training to use.

Peter Kovacs, MD, medical director, Kaali Institute IVF Center, Budapest
Patients: I work as an infertility specialist, so when we talk about infectious diseases and associated risks, we talk about a minimum of two (female and male partner) and ideally three (plus the pregnancy) individuals. We have learned that SARS-CoV-2 affects reproductive health. It may compromise sperm production, could delay fertility treatment, could be associated with lower success rates; and if the treatment is successful, it may harm the pregnant woman/fetus/newborn. The best preventive measure that we can offer is vaccination. One cannot overemphasize the importance of preventive measures, paying attention to personal hygiene and social distancing. Therefore, I wish those planning to become pregnant to listen to their health care provider and accept the recommended vaccines to minimize the risk of getting infected and to minimize the risk for severe disease, especially if one undergoes successful fertility treatment and achieves a long-desired pregnancy.
Practice: During the 2022 calendar year we had many days when one or more employees were out of work on sick leave. This puts extra stress on the others to allow uncompromised work in the clinic. In addition, we all have to work in a less-comfortable environment if we consider mask use every day, all day. For health care workers, vaccination is mandated but many still are affected by milder forms of coronavirus infection and other respiratory diseases. Therefore, I wish my colleagues patience toward the preventive measures to lower the individual risk for infections. As a result, hopefully we will have a less stressful 2023.
Health system: Many resources had to be delegated to dealing with acute and chronic COVID, and this was at the expense of routine daily elective and preventive medical services. I wish the health care system to return to normal daily operations, to have the personnel and financial resources to carry on with the required preventive and elective medical services to avoid long-term consequences of not being able to provide such services. It would be sad if we had to treat otherwise preventable illnesses in the upcoming years that went undiagnosed and/or were not properly managed due to limited resources as the result of the pandemic.

Alan R. Nelson, MD, internist-endocrinologist, retired
Patients: Expansion of the FDA’s authority into over-the-counter drugs, including the veracity of their advertising claims.
Practice: Make diabetes drugs available at a reasonable cost.
Health system: With the expansion of Medicaid eligibility during COVID-19 coming to a close, federal government actions are necessary for those who once again have been dropped from coverage to have their legitimate needs met.

Kevin Powell, MD, PhD, St. Louis
Patients: To be cared for and about, and not just medically, even when illness strikes and health fails.
Hospitals: To hear the thankfulness of a grateful public for the care you provide, and to hear that above the angry noise of outraged individuals who spout vitriol and focus on how they believe others have harmed them.
Health system: A truer understanding of mercy and justice.

Margaret Thew, DNP, FNP-BC, director, department of adolescent medicine, Children’s Hospital of Wisconsin, Milwaukee
Seconded by: M. Susan Jay, MD, professor of pediatrics, chief of adolescent medicine, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee
My wish for patients, hospital, and system: health, calm, and grace.

Mark P. Trolice, MD, director of Fertility CARE, the IVF Center, Winter Park, Fla.
Patients: To be proactive in their health care and be their own advocates. Question when unclear and only consult credible resources.
Practice/hospital: Improve support of physicians and all health care providers to allow more input in their practice operations and growth.
Health system: Reduce interference of the “business of medicine” and ensure that the patient experience is the priority.

Charles P. Vega, MD, University of California, Irvine
Three minutes on a routine basis for everyone in health care to reflect on our blessings and the honor and gravity – as well as joy – that are integral to health care. Three minutes that will also help us to recognize our challenges and put them in the proper context. I know 3 minutes is not meeting any standard for reflective practice. But it’s 3 minutes more than I have right now.

Karen Breach Washington, MD, medical director of WellCare of North Carolina/Centene, Charlotte
Seconded by: Lillian M. Beard, MD, physician director, Children’s Pediatricians and Associates, Silver Spring, Md.
Patients: Access to affordable health care.
Hospital: Resources to care for patients (sufficient number of beds and a healthy staff).
Health system: Equity for all.

Andrew Wilner, MD, host of the podcast “The Art of Medicine with Dr. Andrew Wilner,” www.andrewwilner.com
Let’s put patients first! Too many extraneous considerations other than the patient’s best interest obstruct optimal patient care.

Here are just a few examples of patients coming last instead of first.

• If a patient needs to start a new medication in hospital, we shouldn’t have to wait until the patient is an outpatient because “that’s when insurance will pay.”
• If there’s a new medication that’s better than the old medication, we shouldn’t be forced to choose the old medication and provide inferior care because “that’s when insurance will pay.”
• If patients need to stay in hospital, we shouldn’t be pressured to discharge them because the hospital has decided that decreasing “length of stay” is its highest priority.

Dr. Francis Peabody said it best in 1927: “The secret of the care of the patient is in caring for the patient.” How hard is that?

In 2023, why don’t we follow Dr. Peabody’s sage advice from nearly 100 years ago and see what happens?
 

James M. Wooten, PharmD, University of Missouri–Kansas City, University Health, Kansas City, Mo.
Patients: I want patients to understand and properly realize the advantage of vaccinations – not only for COVID-19 but also for influenza. There is so much misinformation that I spend a lot of time trying to convince patients to get vaccinated. Most patients don’t realize that through their lives, most of them have already been vaccinated for something just to be able to attend school. How the COVID-19 vaccine created so much stigma makes little sense to me. I also want patients to understand that COVID-19 vaccination and boosters do not always prevent infection but will many times prevent severe infection. I believe that better patient communication and education is the key and will always be the key to improving vaccination numbers. Not only communicating and educating patients on vaccination itself but also making patients realize that personal vaccination decisions may affect what happens to your neighbor. Allowing infection means that you may be more likely to infect someone else. As a society, we must take care of each other.
Health system: It will be interesting to see what happens when vaccines are no longer reimbursed by the federal government. Understanding which vaccines work best and are better tolerated will be key to choosing appropriate vaccine brands. Health care providers will need to be very selective regarding which vaccines are selected for formulary inclusion. Thorough meta-analysis studies must be done to provide more evaluable information to allow for appropriate selection. “Knowledge is power!” Appropriate knowledge will help distinguish which vaccines work best for various patient populations.

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

As physicians well know, magic wands don’t exist. If they did, every patient would recover in the exam room, prior authorization wouldn’t exist, and continuing medical education credits would be printed on bearer bonds.

But in the spirit of suspended disbelief, we asked physicians and other contributors what their three wishes would be for their patients, practice/hospital, and health systems. Because, hey – we all need to dream.
 

Suzanne C. Boulter, MD, adjunct professor of pediatrics and community and family medicine, Geisel School of Medicine at Dartmouth, Hanover, N.H.
Patients: An end to gun violence.
Practice/hospital: Adequate staffing and pediatric bed availability.
Health system: Universal access to health insurance.

Sarah G. Candler, MD, MPH, care team medical director and director of academic relations, Iora Primary Care, Northside Clinic, Houston
Patients: Systems of health that start with communities of safety, including access to affordable housing, food, transportation, and health care.
Practice/hospital: I.N.T.E.R.O.P.E.R.A.B.I.L.I.T.Y.
Health system: Clinician leadership that has the power (often aka funding) to do what’s right, not just what’s right in front of us.

Arthur L. Caplan, PhD, bioethicist, New York University Langone Health
Patients: I wish for patients in the United States greater access to affordable primary care. There are still too many people without insurance or a reasonably accessible quality provider. And I especially wish for the rapid expansion of affordable training programs to meet staffing needs, including more scholarships, 3-year programs, and more new primary care–oriented schools.
Hospital: Increased staffing, especially nursing. There are too many retirements, too much burnout, and too much privatization into boutique practices to ensure the ability to provide high-quality, safe, patient-oriented care.
Health system: I wish for health systems to seriously move into electronic medicine. While billing has become electronic, there is still much to be done to supplement diagnosis, training, and standardized data collection on key metrics. Systems are not yet behaving in a manner consistent with the hype in this regard.

Stephen Devries, MD, executive director, Gaples Institute (nonprofit) and adjunct associate professor of nutrition, Harvard School of Public Health, Boston
Patients: Patients continue to demand more from their health care professionals and insist that they are offered evidence-based counseling on nutrition and lifestyle strategies.
Practice: Quality-based reimbursement for medical services will take hold that will incentivize much-needed preventive care.
Hospital: Hospitals will more fully embrace the role of serving as true centers of health and focus as much on preventive medicine as on the more lucrative areas of high-tech treatment.

Peter D. Friedmann, MD, MPH, chief research officer, Baystate Health, Springfield, Mass.
Seconded by: Elisabeth Poorman, MD, general internist, University of Washington Clinic, Kent
Patients: Don’t forget the ongoing epidemic of substance use disorder, a major cause of premature mortality. Descheduling of cannabis and expungement of cannabis-related convictions.
Practice/hospital: Commitment of hospitals and practices to address stigma and ensure delivery of medications for opioid use disorder in primary care, the emergency department, and inpatient settings.
Health system: Reform of antiquated methadone regulations to permit office-based prescription and pharmacy dispensing to treat opioid use disorder, as is the case in most of the world.

Robert Glatter, MD, emergency physician, New York
Patients: I want all patients to understand the enormous strain the health care system has been under – not just with the pandemic, the tripledemic, and mpox [previously called monkeypox], but well before the onset of these public health crises.
Hospital: The medical profession has endured not only burnout but a growing mental health crisis, staffing shortages, a physician addiction crisis, and increased attrition in the decade leading up to the pandemic. The pandemic was like a punch in the gut, occurring at the most inopportune time one could imagine.
Health system: The intersection of health and the state of our public health deserves important mention. Unless we take action to bolster our public health infrastructure, our health care system will be in jeopardy, unable to handle the next pandemic, which could be just around the corner.

William E. Golden, MD, medical director of Arkansas Medicaid, professor of medicine and public health, University of Arkansas for Medical Sciences, Little Rock
Patients: Affordable options for diabetes and obesity management.
Health system: Greater investment by health systems and third-party payers in primary care infrastructure.

Gregory A. Hood, MD, Baptist Health, Lexington, Ky.
Patients: To embrace the gift of getting out in the world, being active, and connecting with others – having put down the screens.
Health system: To be freed from the financial gamesmanship of the insurers as they continue to serve their goals of promoting their hedge fund investing over meaningful and productive partnering with primary care physicians, and that they gain insight that they are one of the main reasons they can’t find PCPs to connect with to render care in disadvantaged environments – because they made it economically impossible to do so.

Robert H. Hopkins Jr., MD, associate professor of internal medicine and pediatrics and director of the division of general internal medicine, University of Arkansas for Medical Sciences, Little Rock
Patients/Health system: I would wish for staged implementation of universal basic health coverage for all, perhaps closest to the French or Canadian model. This would need to be coupled with expanded funding for nursing education, graduate medical education, and tracing of other health-related professionals.

Harvey Hsu, MD, Banner Health, Phoenix
Patients: More clear guidelines that are simple to understand. This can apply to colonoscopy (now age 45), immunizations, blood pressure goals. I wish medications were not as expensive so patients can take the best medicine for them and not stop taking them when they hit their donut hole in coverage.
Practice: We have been functioning on a leaner basis to cut down costs. When the pandemic hit, turnover was high and we lost PAs, nurses, front-office staff, and physicians. Having adequate staffing is probably number one on many lists. One way we dealt with lack of staffing was converting in-person visits to telehealth. Video visits are paid the same as in-person visits, but if the patient could not get their video to work, then it would be a telephone visit. Now many insurances do not even pay for telephone visits. So I would wish that we could still be reimbursed for telehealth visits.
Health system: I would wish for our health system to recognize the extra work required to take care of patients while improving quality and meeting quality measures. Allowing more time for patient visits could be one way to meet those goals or having more support staff to make sure patients get their colonoscopy/mammograms done, improve their sugars, and take their medications.

Jan L. Shifren, MD, Vincent Trustees Professor, obstetrics, gynecology, and reproductive biology, Harvard Medical School, and director of the Midlife Women’s Health Center at Massachusetts General Hospital, Boston
Patients: I wish for patients to be actively involved in all aspects of their care, well informed with shared decision-making.
Practice: I wish for the enormous time demands of electronic medical records and documentation to not distract from the pleasure of caring for patients.
Health system: Patient care remains at the center of decisions and programs.

Timothy J. Joos, MD, MPH, internal medicine/pediatrics, Seattle
Health system: I wish someone could figure out how we could be reimbursed for the quality of care we provide instead of the volume of patients we see. I wish EMRs could become less complicated and more user-friendly rather than needing advanced training to use.

Peter Kovacs, MD, medical director, Kaali Institute IVF Center, Budapest
Patients: I work as an infertility specialist, so when we talk about infectious diseases and associated risks, we talk about a minimum of two (female and male partner) and ideally three (plus the pregnancy) individuals. We have learned that SARS-CoV-2 affects reproductive health. It may compromise sperm production, could delay fertility treatment, could be associated with lower success rates; and if the treatment is successful, it may harm the pregnant woman/fetus/newborn. The best preventive measure that we can offer is vaccination. One cannot overemphasize the importance of preventive measures, paying attention to personal hygiene and social distancing. Therefore, I wish those planning to become pregnant to listen to their health care provider and accept the recommended vaccines to minimize the risk of getting infected and to minimize the risk for severe disease, especially if one undergoes successful fertility treatment and achieves a long-desired pregnancy.
Practice: During the 2022 calendar year we had many days when one or more employees were out of work on sick leave. This puts extra stress on the others to allow uncompromised work in the clinic. In addition, we all have to work in a less-comfortable environment if we consider mask use every day, all day. For health care workers, vaccination is mandated but many still are affected by milder forms of coronavirus infection and other respiratory diseases. Therefore, I wish my colleagues patience toward the preventive measures to lower the individual risk for infections. As a result, hopefully we will have a less stressful 2023.
Health system: Many resources had to be delegated to dealing with acute and chronic COVID, and this was at the expense of routine daily elective and preventive medical services. I wish the health care system to return to normal daily operations, to have the personnel and financial resources to carry on with the required preventive and elective medical services to avoid long-term consequences of not being able to provide such services. It would be sad if we had to treat otherwise preventable illnesses in the upcoming years that went undiagnosed and/or were not properly managed due to limited resources as the result of the pandemic.

Alan R. Nelson, MD, internist-endocrinologist, retired
Patients: Expansion of the FDA’s authority into over-the-counter drugs, including the veracity of their advertising claims.
Practice: Make diabetes drugs available at a reasonable cost.
Health system: With the expansion of Medicaid eligibility during COVID-19 coming to a close, federal government actions are necessary for those who once again have been dropped from coverage to have their legitimate needs met.

Kevin Powell, MD, PhD, St. Louis
Patients: To be cared for and about, and not just medically, even when illness strikes and health fails.
Hospitals: To hear the thankfulness of a grateful public for the care you provide, and to hear that above the angry noise of outraged individuals who spout vitriol and focus on how they believe others have harmed them.
Health system: A truer understanding of mercy and justice.

Margaret Thew, DNP, FNP-BC, director, department of adolescent medicine, Children’s Hospital of Wisconsin, Milwaukee
Seconded by: M. Susan Jay, MD, professor of pediatrics, chief of adolescent medicine, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee
My wish for patients, hospital, and system: health, calm, and grace.

Mark P. Trolice, MD, director of Fertility CARE, the IVF Center, Winter Park, Fla.
Patients: To be proactive in their health care and be their own advocates. Question when unclear and only consult credible resources.
Practice/hospital: Improve support of physicians and all health care providers to allow more input in their practice operations and growth.
Health system: Reduce interference of the “business of medicine” and ensure that the patient experience is the priority.

Charles P. Vega, MD, University of California, Irvine
Three minutes on a routine basis for everyone in health care to reflect on our blessings and the honor and gravity – as well as joy – that are integral to health care. Three minutes that will also help us to recognize our challenges and put them in the proper context. I know 3 minutes is not meeting any standard for reflective practice. But it’s 3 minutes more than I have right now.

Karen Breach Washington, MD, medical director of WellCare of North Carolina/Centene, Charlotte
Seconded by: Lillian M. Beard, MD, physician director, Children’s Pediatricians and Associates, Silver Spring, Md.
Patients: Access to affordable health care.
Hospital: Resources to care for patients (sufficient number of beds and a healthy staff).
Health system: Equity for all.

Andrew Wilner, MD, host of the podcast “The Art of Medicine with Dr. Andrew Wilner,” www.andrewwilner.com
Let’s put patients first! Too many extraneous considerations other than the patient’s best interest obstruct optimal patient care.

Here are just a few examples of patients coming last instead of first.

• If a patient needs to start a new medication in hospital, we shouldn’t have to wait until the patient is an outpatient because “that’s when insurance will pay.”
• If there’s a new medication that’s better than the old medication, we shouldn’t be forced to choose the old medication and provide inferior care because “that’s when insurance will pay.”
• If patients need to stay in hospital, we shouldn’t be pressured to discharge them because the hospital has decided that decreasing “length of stay” is its highest priority.

Dr. Francis Peabody said it best in 1927: “The secret of the care of the patient is in caring for the patient.” How hard is that?

In 2023, why don’t we follow Dr. Peabody’s sage advice from nearly 100 years ago and see what happens?
 

James M. Wooten, PharmD, University of Missouri–Kansas City, University Health, Kansas City, Mo.
Patients: I want patients to understand and properly realize the advantage of vaccinations – not only for COVID-19 but also for influenza. There is so much misinformation that I spend a lot of time trying to convince patients to get vaccinated. Most patients don’t realize that through their lives, most of them have already been vaccinated for something just to be able to attend school. How the COVID-19 vaccine created so much stigma makes little sense to me. I also want patients to understand that COVID-19 vaccination and boosters do not always prevent infection but will many times prevent severe infection. I believe that better patient communication and education is the key and will always be the key to improving vaccination numbers. Not only communicating and educating patients on vaccination itself but also making patients realize that personal vaccination decisions may affect what happens to your neighbor. Allowing infection means that you may be more likely to infect someone else. As a society, we must take care of each other.
Health system: It will be interesting to see what happens when vaccines are no longer reimbursed by the federal government. Understanding which vaccines work best and are better tolerated will be key to choosing appropriate vaccine brands. Health care providers will need to be very selective regarding which vaccines are selected for formulary inclusion. Thorough meta-analysis studies must be done to provide more evaluable information to allow for appropriate selection. “Knowledge is power!” Appropriate knowledge will help distinguish which vaccines work best for various patient populations.

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

As physicians well know, magic wands don’t exist. If they did, every patient would recover in the exam room, prior authorization wouldn’t exist, and continuing medical education credits would be printed on bearer bonds.

But in the spirit of suspended disbelief, we asked physicians and other contributors what their three wishes would be for their patients, practice/hospital, and health systems. Because, hey – we all need to dream.
 

Suzanne C. Boulter, MD, adjunct professor of pediatrics and community and family medicine, Geisel School of Medicine at Dartmouth, Hanover, N.H.
Patients: An end to gun violence.
Practice/hospital: Adequate staffing and pediatric bed availability.
Health system: Universal access to health insurance.

Sarah G. Candler, MD, MPH, care team medical director and director of academic relations, Iora Primary Care, Northside Clinic, Houston
Patients: Systems of health that start with communities of safety, including access to affordable housing, food, transportation, and health care.
Practice/hospital: I.N.T.E.R.O.P.E.R.A.B.I.L.I.T.Y.
Health system: Clinician leadership that has the power (often aka funding) to do what’s right, not just what’s right in front of us.

Arthur L. Caplan, PhD, bioethicist, New York University Langone Health
Patients: I wish for patients in the United States greater access to affordable primary care. There are still too many people without insurance or a reasonably accessible quality provider. And I especially wish for the rapid expansion of affordable training programs to meet staffing needs, including more scholarships, 3-year programs, and more new primary care–oriented schools.
Hospital: Increased staffing, especially nursing. There are too many retirements, too much burnout, and too much privatization into boutique practices to ensure the ability to provide high-quality, safe, patient-oriented care.
Health system: I wish for health systems to seriously move into electronic medicine. While billing has become electronic, there is still much to be done to supplement diagnosis, training, and standardized data collection on key metrics. Systems are not yet behaving in a manner consistent with the hype in this regard.

Stephen Devries, MD, executive director, Gaples Institute (nonprofit) and adjunct associate professor of nutrition, Harvard School of Public Health, Boston
Patients: Patients continue to demand more from their health care professionals and insist that they are offered evidence-based counseling on nutrition and lifestyle strategies.
Practice: Quality-based reimbursement for medical services will take hold that will incentivize much-needed preventive care.
Hospital: Hospitals will more fully embrace the role of serving as true centers of health and focus as much on preventive medicine as on the more lucrative areas of high-tech treatment.

Peter D. Friedmann, MD, MPH, chief research officer, Baystate Health, Springfield, Mass.
Seconded by: Elisabeth Poorman, MD, general internist, University of Washington Clinic, Kent
Patients: Don’t forget the ongoing epidemic of substance use disorder, a major cause of premature mortality. Descheduling of cannabis and expungement of cannabis-related convictions.
Practice/hospital: Commitment of hospitals and practices to address stigma and ensure delivery of medications for opioid use disorder in primary care, the emergency department, and inpatient settings.
Health system: Reform of antiquated methadone regulations to permit office-based prescription and pharmacy dispensing to treat opioid use disorder, as is the case in most of the world.

Robert Glatter, MD, emergency physician, New York
Patients: I want all patients to understand the enormous strain the health care system has been under – not just with the pandemic, the tripledemic, and mpox [previously called monkeypox], but well before the onset of these public health crises.
Hospital: The medical profession has endured not only burnout but a growing mental health crisis, staffing shortages, a physician addiction crisis, and increased attrition in the decade leading up to the pandemic. The pandemic was like a punch in the gut, occurring at the most inopportune time one could imagine.
Health system: The intersection of health and the state of our public health deserves important mention. Unless we take action to bolster our public health infrastructure, our health care system will be in jeopardy, unable to handle the next pandemic, which could be just around the corner.

William E. Golden, MD, medical director of Arkansas Medicaid, professor of medicine and public health, University of Arkansas for Medical Sciences, Little Rock
Patients: Affordable options for diabetes and obesity management.
Health system: Greater investment by health systems and third-party payers in primary care infrastructure.

Gregory A. Hood, MD, Baptist Health, Lexington, Ky.
Patients: To embrace the gift of getting out in the world, being active, and connecting with others – having put down the screens.
Health system: To be freed from the financial gamesmanship of the insurers as they continue to serve their goals of promoting their hedge fund investing over meaningful and productive partnering with primary care physicians, and that they gain insight that they are one of the main reasons they can’t find PCPs to connect with to render care in disadvantaged environments – because they made it economically impossible to do so.

Robert H. Hopkins Jr., MD, associate professor of internal medicine and pediatrics and director of the division of general internal medicine, University of Arkansas for Medical Sciences, Little Rock
Patients/Health system: I would wish for staged implementation of universal basic health coverage for all, perhaps closest to the French or Canadian model. This would need to be coupled with expanded funding for nursing education, graduate medical education, and tracing of other health-related professionals.

Harvey Hsu, MD, Banner Health, Phoenix
Patients: More clear guidelines that are simple to understand. This can apply to colonoscopy (now age 45), immunizations, blood pressure goals. I wish medications were not as expensive so patients can take the best medicine for them and not stop taking them when they hit their donut hole in coverage.
Practice: We have been functioning on a leaner basis to cut down costs. When the pandemic hit, turnover was high and we lost PAs, nurses, front-office staff, and physicians. Having adequate staffing is probably number one on many lists. One way we dealt with lack of staffing was converting in-person visits to telehealth. Video visits are paid the same as in-person visits, but if the patient could not get their video to work, then it would be a telephone visit. Now many insurances do not even pay for telephone visits. So I would wish that we could still be reimbursed for telehealth visits.
Health system: I would wish for our health system to recognize the extra work required to take care of patients while improving quality and meeting quality measures. Allowing more time for patient visits could be one way to meet those goals or having more support staff to make sure patients get their colonoscopy/mammograms done, improve their sugars, and take their medications.

Jan L. Shifren, MD, Vincent Trustees Professor, obstetrics, gynecology, and reproductive biology, Harvard Medical School, and director of the Midlife Women’s Health Center at Massachusetts General Hospital, Boston
Patients: I wish for patients to be actively involved in all aspects of their care, well informed with shared decision-making.
Practice: I wish for the enormous time demands of electronic medical records and documentation to not distract from the pleasure of caring for patients.
Health system: Patient care remains at the center of decisions and programs.

Timothy J. Joos, MD, MPH, internal medicine/pediatrics, Seattle
Health system: I wish someone could figure out how we could be reimbursed for the quality of care we provide instead of the volume of patients we see. I wish EMRs could become less complicated and more user-friendly rather than needing advanced training to use.

Peter Kovacs, MD, medical director, Kaali Institute IVF Center, Budapest
Patients: I work as an infertility specialist, so when we talk about infectious diseases and associated risks, we talk about a minimum of two (female and male partner) and ideally three (plus the pregnancy) individuals. We have learned that SARS-CoV-2 affects reproductive health. It may compromise sperm production, could delay fertility treatment, could be associated with lower success rates; and if the treatment is successful, it may harm the pregnant woman/fetus/newborn. The best preventive measure that we can offer is vaccination. One cannot overemphasize the importance of preventive measures, paying attention to personal hygiene and social distancing. Therefore, I wish those planning to become pregnant to listen to their health care provider and accept the recommended vaccines to minimize the risk of getting infected and to minimize the risk for severe disease, especially if one undergoes successful fertility treatment and achieves a long-desired pregnancy.
Practice: During the 2022 calendar year we had many days when one or more employees were out of work on sick leave. This puts extra stress on the others to allow uncompromised work in the clinic. In addition, we all have to work in a less-comfortable environment if we consider mask use every day, all day. For health care workers, vaccination is mandated but many still are affected by milder forms of coronavirus infection and other respiratory diseases. Therefore, I wish my colleagues patience toward the preventive measures to lower the individual risk for infections. As a result, hopefully we will have a less stressful 2023.
Health system: Many resources had to be delegated to dealing with acute and chronic COVID, and this was at the expense of routine daily elective and preventive medical services. I wish the health care system to return to normal daily operations, to have the personnel and financial resources to carry on with the required preventive and elective medical services to avoid long-term consequences of not being able to provide such services. It would be sad if we had to treat otherwise preventable illnesses in the upcoming years that went undiagnosed and/or were not properly managed due to limited resources as the result of the pandemic.

Alan R. Nelson, MD, internist-endocrinologist, retired
Patients: Expansion of the FDA’s authority into over-the-counter drugs, including the veracity of their advertising claims.
Practice: Make diabetes drugs available at a reasonable cost.
Health system: With the expansion of Medicaid eligibility during COVID-19 coming to a close, federal government actions are necessary for those who once again have been dropped from coverage to have their legitimate needs met.

Kevin Powell, MD, PhD, St. Louis
Patients: To be cared for and about, and not just medically, even when illness strikes and health fails.
Hospitals: To hear the thankfulness of a grateful public for the care you provide, and to hear that above the angry noise of outraged individuals who spout vitriol and focus on how they believe others have harmed them.
Health system: A truer understanding of mercy and justice.

Margaret Thew, DNP, FNP-BC, director, department of adolescent medicine, Children’s Hospital of Wisconsin, Milwaukee
Seconded by: M. Susan Jay, MD, professor of pediatrics, chief of adolescent medicine, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee
My wish for patients, hospital, and system: health, calm, and grace.

Mark P. Trolice, MD, director of Fertility CARE, the IVF Center, Winter Park, Fla.
Patients: To be proactive in their health care and be their own advocates. Question when unclear and only consult credible resources.
Practice/hospital: Improve support of physicians and all health care providers to allow more input in their practice operations and growth.
Health system: Reduce interference of the “business of medicine” and ensure that the patient experience is the priority.

Charles P. Vega, MD, University of California, Irvine
Three minutes on a routine basis for everyone in health care to reflect on our blessings and the honor and gravity – as well as joy – that are integral to health care. Three minutes that will also help us to recognize our challenges and put them in the proper context. I know 3 minutes is not meeting any standard for reflective practice. But it’s 3 minutes more than I have right now.

Karen Breach Washington, MD, medical director of WellCare of North Carolina/Centene, Charlotte
Seconded by: Lillian M. Beard, MD, physician director, Children’s Pediatricians and Associates, Silver Spring, Md.
Patients: Access to affordable health care.
Hospital: Resources to care for patients (sufficient number of beds and a healthy staff).
Health system: Equity for all.

Andrew Wilner, MD, host of the podcast “The Art of Medicine with Dr. Andrew Wilner,” www.andrewwilner.com
Let’s put patients first! Too many extraneous considerations other than the patient’s best interest obstruct optimal patient care.

Here are just a few examples of patients coming last instead of first.

• If a patient needs to start a new medication in hospital, we shouldn’t have to wait until the patient is an outpatient because “that’s when insurance will pay.”
• If there’s a new medication that’s better than the old medication, we shouldn’t be forced to choose the old medication and provide inferior care because “that’s when insurance will pay.”
• If patients need to stay in hospital, we shouldn’t be pressured to discharge them because the hospital has decided that decreasing “length of stay” is its highest priority.

Dr. Francis Peabody said it best in 1927: “The secret of the care of the patient is in caring for the patient.” How hard is that?

In 2023, why don’t we follow Dr. Peabody’s sage advice from nearly 100 years ago and see what happens?
 

James M. Wooten, PharmD, University of Missouri–Kansas City, University Health, Kansas City, Mo.
Patients: I want patients to understand and properly realize the advantage of vaccinations – not only for COVID-19 but also for influenza. There is so much misinformation that I spend a lot of time trying to convince patients to get vaccinated. Most patients don’t realize that through their lives, most of them have already been vaccinated for something just to be able to attend school. How the COVID-19 vaccine created so much stigma makes little sense to me. I also want patients to understand that COVID-19 vaccination and boosters do not always prevent infection but will many times prevent severe infection. I believe that better patient communication and education is the key and will always be the key to improving vaccination numbers. Not only communicating and educating patients on vaccination itself but also making patients realize that personal vaccination decisions may affect what happens to your neighbor. Allowing infection means that you may be more likely to infect someone else. As a society, we must take care of each other.
Health system: It will be interesting to see what happens when vaccines are no longer reimbursed by the federal government. Understanding which vaccines work best and are better tolerated will be key to choosing appropriate vaccine brands. Health care providers will need to be very selective regarding which vaccines are selected for formulary inclusion. Thorough meta-analysis studies must be done to provide more evaluable information to allow for appropriate selection. “Knowledge is power!” Appropriate knowledge will help distinguish which vaccines work best for various patient populations.

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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