Depression

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

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

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

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

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

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

Expanding suicide risk screening in primary care to identify patients at highest risk may help boost prevention efforts and make better use of health care resources, according to a new study.

Craig J. Bryan, PsyD, ABPP, with the department of psychiatry and behavioral health at Ohio State University Wexner Medical Center, Columbus, led the study, published online on Nov. 8, 2021, in Annals of Family Medicine.

The authors cited the urgency highlighted by statistics showing that, from 1999 to 2017, the U.S. suicide rate increased by more than 33% and was particularly high among military personnel and veterans.

Primary care offices are seen as a prime target for prevention efforts as nearly one-half of people who die by suicide in the United States visit a primary care office in the months before their deaths.

A common approach to screening for suicide risk has been to use the Patient Health Questionnaire–9 (PHQ-9). The first two questions assess the frequency of depressed mood and anhedonia in the past 2 weeks. If patients screen positive on those two questions, they are given the remaining seven questions.

A single item – question 9 – asks about how often a patient has “thoughts that you would be better off dead, or of hurting yourself in some way” during the past 2 weeks.

Yet, more that 95% of patients who screen positive on the PHQ-9 suicide risk question do not attempt or die by suicide, the authors noted.
 

Two methods tested for improving screening

Dr. Bryan and colleagues wanted to assess whether suicide risk screening could be improved in primary care and evaluated two methods.

One was to see whether using any of the other PHQ-9 items could be better than just using item 9 alone to identify the patients who were most likely to attempt suicide in the near future. Researchers found that method was not significantly beneficial. The second was to evaluate the performance of the 16 items on the Suicide Cognitions Scale (SCS), a questionnaire that asks patients to rate the extent to which they agree or disagree with statements that are commonly endorsed by suicidal people.

Patients who were eligible for medical treatment from the Department of Defense medical system were recruited from six large and small military primary care clinics across the United States from July 2015 to August 2018.

Patients answered questions on the PHQ-9 and 16 items from the SCS during routine primary care visits. Evaluators, who were blind to screening results, assessed postbaseline suicide attempts, interrupted attempts and aborted attempts by interviewing patients.

The study included 2,744 primary care patients, ranging from 18 to 89 years of age, with an average age of 40.
 

Adding at least one question may help

Researchers found that the accuracy of suicide risk screening using the PHQ-9 can be significantly improved by adding one or more questions from the SCS. Three items from SCS contributed most to meaningful improvements in identifying patients who went on to exhibit suicidal behaviors within 30-90 days of screening.

One question was item 16: “I don’t deserve to live another moment.”

Two SCS items improved specificity and positive predictive value without reducing sensitivity, the authors wrote. They are: “It is unbearable when I get this upset” (item 8) and “I can’t imagine anyone being able to withstand this kind of pain” (item 13).

“For example,” the authors wrote, “only 4.1% of patients who screened positive on the PHQ-9 suicide risk item 9 engaged in suicidal behavior within the next 30 days, but when the PHQ-9 suicide risk item 9 was combined with SCS item 13 (the best-performing SCS item), this percentage nearly doubled, to 7.6% of patients.”

Adding one of these SCS items to the PHQ-9 “could provide a simple, accessible, and low-cost method for more accurately identifying primary care patients who require more immediate clinical intervention,” the authors wrote.
 

Outside expert perspective

Meredith Williamson, PhD, a mental health diagnosis and psychotherapy expert and clinical assistant professor at Texas A&M University, Bryan, said that, though the SCS questions are valuable, neither they nor the PHQ-9 question get to the direct question of whether the person is likely to act on their thoughts and attempt or complete suicide.

“Someone with depression may have thought of wishing they were dead or wishing they weren’t here but that doesn’t always mean they necessarily want to kill themselves,” she said in an interview. “It’s our responsibility as providers to really clarify the meaning of that item.”

Dr. Williamson noted the PHQ-9 is a very accessible method to screen for depression in primary care settings and is a way to catch large numbers of people screening positive, but its shortcomings are well known and additional information is needed.

She said that, in her practice, if a patient screens positive on PHQ-9, clinicians ask more about their intentions, how frequently they occur and whether patients have developed a plan for killing themselves.

The challenge is that “we have yet to predict who is and who is not going to kill themselves.”

Dr. Williamson said she finds the Columbia-Suicide Severity Rating Scale a valuable tool used in research settings that looks at prior attempts and current desire to engage in an attempt in more detail.

“It doesn’t stop people from killing themselves, but helps to better understand their suicidal behavior,” she explained.

This project was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program. Dr. Williamson has no relevant financial disclosures. Dr. Bryan is a paid consultant to Oui Therapeutics and Neurostat Analytical Solutions. He is a principal of Anduril, which conducts training workshops and provides mental health consultation focused on suicide prevention and PTSD.

Expanding suicide risk screening in primary care to identify patients at highest risk may help boost prevention efforts and make better use of health care resources, according to a new study.

Craig J. Bryan, PsyD, ABPP, with the department of psychiatry and behavioral health at Ohio State University Wexner Medical Center, Columbus, led the study, published online on Nov. 8, 2021, in Annals of Family Medicine.

The authors cited the urgency highlighted by statistics showing that, from 1999 to 2017, the U.S. suicide rate increased by more than 33% and was particularly high among military personnel and veterans.

Primary care offices are seen as a prime target for prevention efforts as nearly one-half of people who die by suicide in the United States visit a primary care office in the months before their deaths.

A common approach to screening for suicide risk has been to use the Patient Health Questionnaire–9 (PHQ-9). The first two questions assess the frequency of depressed mood and anhedonia in the past 2 weeks. If patients screen positive on those two questions, they are given the remaining seven questions.

A single item – question 9 – asks about how often a patient has “thoughts that you would be better off dead, or of hurting yourself in some way” during the past 2 weeks.

Yet, more that 95% of patients who screen positive on the PHQ-9 suicide risk question do not attempt or die by suicide, the authors noted.
 

Two methods tested for improving screening

Dr. Bryan and colleagues wanted to assess whether suicide risk screening could be improved in primary care and evaluated two methods.

One was to see whether using any of the other PHQ-9 items could be better than just using item 9 alone to identify the patients who were most likely to attempt suicide in the near future. Researchers found that method was not significantly beneficial. The second was to evaluate the performance of the 16 items on the Suicide Cognitions Scale (SCS), a questionnaire that asks patients to rate the extent to which they agree or disagree with statements that are commonly endorsed by suicidal people.

Patients who were eligible for medical treatment from the Department of Defense medical system were recruited from six large and small military primary care clinics across the United States from July 2015 to August 2018.

Patients answered questions on the PHQ-9 and 16 items from the SCS during routine primary care visits. Evaluators, who were blind to screening results, assessed postbaseline suicide attempts, interrupted attempts and aborted attempts by interviewing patients.

The study included 2,744 primary care patients, ranging from 18 to 89 years of age, with an average age of 40.
 

Adding at least one question may help

Researchers found that the accuracy of suicide risk screening using the PHQ-9 can be significantly improved by adding one or more questions from the SCS. Three items from SCS contributed most to meaningful improvements in identifying patients who went on to exhibit suicidal behaviors within 30-90 days of screening.

One question was item 16: “I don’t deserve to live another moment.”

Two SCS items improved specificity and positive predictive value without reducing sensitivity, the authors wrote. They are: “It is unbearable when I get this upset” (item 8) and “I can’t imagine anyone being able to withstand this kind of pain” (item 13).

“For example,” the authors wrote, “only 4.1% of patients who screened positive on the PHQ-9 suicide risk item 9 engaged in suicidal behavior within the next 30 days, but when the PHQ-9 suicide risk item 9 was combined with SCS item 13 (the best-performing SCS item), this percentage nearly doubled, to 7.6% of patients.”

Adding one of these SCS items to the PHQ-9 “could provide a simple, accessible, and low-cost method for more accurately identifying primary care patients who require more immediate clinical intervention,” the authors wrote.
 

Outside expert perspective

Meredith Williamson, PhD, a mental health diagnosis and psychotherapy expert and clinical assistant professor at Texas A&M University, Bryan, said that, though the SCS questions are valuable, neither they nor the PHQ-9 question get to the direct question of whether the person is likely to act on their thoughts and attempt or complete suicide.

“Someone with depression may have thought of wishing they were dead or wishing they weren’t here but that doesn’t always mean they necessarily want to kill themselves,” she said in an interview. “It’s our responsibility as providers to really clarify the meaning of that item.”

Dr. Williamson noted the PHQ-9 is a very accessible method to screen for depression in primary care settings and is a way to catch large numbers of people screening positive, but its shortcomings are well known and additional information is needed.

She said that, in her practice, if a patient screens positive on PHQ-9, clinicians ask more about their intentions, how frequently they occur and whether patients have developed a plan for killing themselves.

The challenge is that “we have yet to predict who is and who is not going to kill themselves.”

Dr. Williamson said she finds the Columbia-Suicide Severity Rating Scale a valuable tool used in research settings that looks at prior attempts and current desire to engage in an attempt in more detail.

“It doesn’t stop people from killing themselves, but helps to better understand their suicidal behavior,” she explained.

This project was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program. Dr. Williamson has no relevant financial disclosures. Dr. Bryan is a paid consultant to Oui Therapeutics and Neurostat Analytical Solutions. He is a principal of Anduril, which conducts training workshops and provides mental health consultation focused on suicide prevention and PTSD.

Expanding suicide risk screening in primary care to identify patients at highest risk may help boost prevention efforts and make better use of health care resources, according to a new study.

Craig J. Bryan, PsyD, ABPP, with the department of psychiatry and behavioral health at Ohio State University Wexner Medical Center, Columbus, led the study, published online on Nov. 8, 2021, in Annals of Family Medicine.

The authors cited the urgency highlighted by statistics showing that, from 1999 to 2017, the U.S. suicide rate increased by more than 33% and was particularly high among military personnel and veterans.

Primary care offices are seen as a prime target for prevention efforts as nearly one-half of people who die by suicide in the United States visit a primary care office in the months before their deaths.

A common approach to screening for suicide risk has been to use the Patient Health Questionnaire–9 (PHQ-9). The first two questions assess the frequency of depressed mood and anhedonia in the past 2 weeks. If patients screen positive on those two questions, they are given the remaining seven questions.

A single item – question 9 – asks about how often a patient has “thoughts that you would be better off dead, or of hurting yourself in some way” during the past 2 weeks.

Yet, more that 95% of patients who screen positive on the PHQ-9 suicide risk question do not attempt or die by suicide, the authors noted.
 

Two methods tested for improving screening

Dr. Bryan and colleagues wanted to assess whether suicide risk screening could be improved in primary care and evaluated two methods.

One was to see whether using any of the other PHQ-9 items could be better than just using item 9 alone to identify the patients who were most likely to attempt suicide in the near future. Researchers found that method was not significantly beneficial. The second was to evaluate the performance of the 16 items on the Suicide Cognitions Scale (SCS), a questionnaire that asks patients to rate the extent to which they agree or disagree with statements that are commonly endorsed by suicidal people.

Patients who were eligible for medical treatment from the Department of Defense medical system were recruited from six large and small military primary care clinics across the United States from July 2015 to August 2018.

Patients answered questions on the PHQ-9 and 16 items from the SCS during routine primary care visits. Evaluators, who were blind to screening results, assessed postbaseline suicide attempts, interrupted attempts and aborted attempts by interviewing patients.

The study included 2,744 primary care patients, ranging from 18 to 89 years of age, with an average age of 40.
 

Adding at least one question may help

Researchers found that the accuracy of suicide risk screening using the PHQ-9 can be significantly improved by adding one or more questions from the SCS. Three items from SCS contributed most to meaningful improvements in identifying patients who went on to exhibit suicidal behaviors within 30-90 days of screening.

One question was item 16: “I don’t deserve to live another moment.”

Two SCS items improved specificity and positive predictive value without reducing sensitivity, the authors wrote. They are: “It is unbearable when I get this upset” (item 8) and “I can’t imagine anyone being able to withstand this kind of pain” (item 13).

“For example,” the authors wrote, “only 4.1% of patients who screened positive on the PHQ-9 suicide risk item 9 engaged in suicidal behavior within the next 30 days, but when the PHQ-9 suicide risk item 9 was combined with SCS item 13 (the best-performing SCS item), this percentage nearly doubled, to 7.6% of patients.”

Adding one of these SCS items to the PHQ-9 “could provide a simple, accessible, and low-cost method for more accurately identifying primary care patients who require more immediate clinical intervention,” the authors wrote.
 

Outside expert perspective

Meredith Williamson, PhD, a mental health diagnosis and psychotherapy expert and clinical assistant professor at Texas A&M University, Bryan, said that, though the SCS questions are valuable, neither they nor the PHQ-9 question get to the direct question of whether the person is likely to act on their thoughts and attempt or complete suicide.

“Someone with depression may have thought of wishing they were dead or wishing they weren’t here but that doesn’t always mean they necessarily want to kill themselves,” she said in an interview. “It’s our responsibility as providers to really clarify the meaning of that item.”

Dr. Williamson noted the PHQ-9 is a very accessible method to screen for depression in primary care settings and is a way to catch large numbers of people screening positive, but its shortcomings are well known and additional information is needed.

She said that, in her practice, if a patient screens positive on PHQ-9, clinicians ask more about their intentions, how frequently they occur and whether patients have developed a plan for killing themselves.

The challenge is that “we have yet to predict who is and who is not going to kill themselves.”

Dr. Williamson said she finds the Columbia-Suicide Severity Rating Scale a valuable tool used in research settings that looks at prior attempts and current desire to engage in an attempt in more detail.

“It doesn’t stop people from killing themselves, but helps to better understand their suicidal behavior,” she explained.

This project was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program. Dr. Williamson has no relevant financial disclosures. Dr. Bryan is a paid consultant to Oui Therapeutics and Neurostat Analytical Solutions. He is a principal of Anduril, which conducts training workshops and provides mental health consultation focused on suicide prevention and PTSD.

Recent research suggests that some pediatric patients who develop neuropsychiatric symptoms from COVID-19 may have intrathecal antineural SARS-CoV-2 autoantibodies, which may hint at central nervous system (CNS) autoimmunity in these patients.

“Overall, these findings indicate that severe neuropsychiatric symptoms can occur in the setting of pediatric COVID-19, including patients who lack many of the cardinal systemic features,” Christopher M. Bartley, MD, PhD, of the Weill Institute for Neurosciences at the University of California, San Francisco, and colleagues wrote in their study. “These data highlight the possibility of SARS-CoV-2 neuroinvasion and/or CNS autoimmunity in pediatric patients with COVID-19 and neuropsychiatric symptoms.”

In a case series published Oct. 25 in JAMA Neurology (doi: 10.1001/jamaneurol.2021.3821), Dr. Bartley and colleagues examined three pediatric patients who were infected with SARS-CoV-2 and, over a period of 5 months in 2020, were admitted to the hospital – where they received a neurology consultation for “subacute, functionally impairing behavioral changes.”

Patient 1 had a history of unspecified anxiety and depression, and was admitted for erratic behavior, paranoia-like fears, social withdrawal, and insomnia. The patient did not respond to treatment with risperidone and gabapentin, and was readmitted soon after discharge, then treated with olanzapine followed by a transition to valproate and lorazepam. It was found the patient had cerebrospinal fluid (CSF) abnormalities in the form of elevated protein levels, and an elevated IgG index, and was given intravenous immunoglobulin followed by IV methylprednisolone. While symptoms such as paranoia improved and the patient was able to better organize thoughts after 5 days, other symptoms such as delusions and hyperreflexia persisted for at least 1 month before resolving, and some symptoms, such as lability, did not resolve before discharge.

Patient 2 had a history of motor tics and anxiety, but showed signs of insomnia, mood lability, impaired concentration, difficulty finding words, and problems completing homework following a SARS-CoV-2 infection. The patient’s father previously had been diagnosed with COVID-19 and the patient developed respiratory symptoms and fever; an IgG serology test later confirmed a SARS-CoV-2 infection. The patient went on to experience internal preoccupation, aggression, and suicidal ideation. The patients was treated with aripiprazole and risperidone, but did not respond, and was admitted to the hospital. As with patient 1, patient 2 had CSF abnormalities in the form of elevated protein levels, and responded to IV methylprednisolone, with working memory and bradyphrenia improving. However, the patient developed insomnia, extreme anxiety, suicidal ideation, aggression, and sadness after discharge, and was readmitted. The patient was treated with IV immunoglobulin, and discharged with quetiapine and lithium.

“Six months later, although improved from initial presentation, the patient required academic accommodations and continued to endorse forgetfulness and attention difficulties. The patient’s chronic tics and anxiety were unchanged,” Dr. Bartley and colleagues wrote.

Patient 3 had no psychiatric history but started to demonstrate “odd behavior, including repetitive behaviors, anorexia, and insomnia” following a SARS-CoV-2 infection. After being hospitalized, the patient showed signs of “ideomotor apraxia, abulia, disorganized behavior, agitation, and diffusely brisk reflexes” and had a high white blood cell count, creatine kinase level, and C-reactive protein level. CSF was also abnormal for this patient, with three unique oligoclonal bands identified. The patient was treated with lorazepam and olanzapine, did not receive immunotherapy, and was discharged without psychiatric medications after 4 days.

When the researchers performed testing on each of the three patients, they found intrathecal anti–SARS-CoV-2 IgG and immunostained mouse brain tissue, and “a diverse set of candidate autoantigens by human phage immunoprecipitation sequencing” in patient 1 and patient 2. In comparison, patient 3 “neither appreciably immunostained nor enriched candidates by human phage immunoprecipitation sequencing,” the researchers said.

“These data motivate a systematic study of humoral immunity in the CSF of pediatric patients with COVID-19 and neuropsychiatric involvement and the potential for immunotherapy in some,” Dr. Bartley and colleagues concluded.
 

Potential of CNS autoimmunity

Evan J. Kyzar, MD, PhD, a resident physician in psychiatry at New York State Psychiatric Institute in New York Presbyterian–Columbia Campus, said in an interview that the results of the case series show some pediatric patients with neuropsychiatric symptoms can have anti-SARS-CoV-2 antibodies after viral clearance.

“Interestingly, some of the patients in this study also had antibodies in the CSF that targeted native proteins, demonstrating that COVID-19 may lead to autoimmunity directed at the brain,” he said. “This study increases our knowledge of how COVID-19 interacts with the nervous system and how autoimmune mechanisms might be contributing to at least a portion of patients with neuropsychiatric symptoms during acute infection, and possibly even after viral clearance.”

Dr. Kyzar noted that the immunological methods in the study were “cutting-edge” and the validation exploring the immune responses was detailed, but was limited because of the small sample size.

“[T]he researchers are using similar techniques to explore psychiatric disorders such as depression and schizophrenia to determine if some patients diagnosed with these conditions may have CNS-targeting autoantibodies that contribute to their symptoms and clinical presentation,” Dr. Kyzar said. “This work has the potential to discover novel neuroimmune mechanisms contributing to neuropsychiatric disease and offer possible pathways for the discovery of new treatments.”

The authors reported financial relationships with Allen & Company, the Chan Zuckerberg Initiative, National Institutes of Health, Novartis, Public Health Company, Roche/Genentech, Sandler Foundation, and Takeda in the form of grants and personal fees. They reported funding and/or support from the Brain Research Foundation, Hanna H. Gray Fellowship, Howard Hughes Medical Institute, John A. Watson Scholar Program, Latinx Center of Excellence, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, President’s Postdoctoral Fellowship Program, and Shared Instrumentation grant. Dr. Kyzar reported no relevant financial disclosures.

Recent research suggests that some pediatric patients who develop neuropsychiatric symptoms from COVID-19 may have intrathecal antineural SARS-CoV-2 autoantibodies, which may hint at central nervous system (CNS) autoimmunity in these patients.

“Overall, these findings indicate that severe neuropsychiatric symptoms can occur in the setting of pediatric COVID-19, including patients who lack many of the cardinal systemic features,” Christopher M. Bartley, MD, PhD, of the Weill Institute for Neurosciences at the University of California, San Francisco, and colleagues wrote in their study. “These data highlight the possibility of SARS-CoV-2 neuroinvasion and/or CNS autoimmunity in pediatric patients with COVID-19 and neuropsychiatric symptoms.”

In a case series published Oct. 25 in JAMA Neurology (doi: 10.1001/jamaneurol.2021.3821), Dr. Bartley and colleagues examined three pediatric patients who were infected with SARS-CoV-2 and, over a period of 5 months in 2020, were admitted to the hospital – where they received a neurology consultation for “subacute, functionally impairing behavioral changes.”

Patient 1 had a history of unspecified anxiety and depression, and was admitted for erratic behavior, paranoia-like fears, social withdrawal, and insomnia. The patient did not respond to treatment with risperidone and gabapentin, and was readmitted soon after discharge, then treated with olanzapine followed by a transition to valproate and lorazepam. It was found the patient had cerebrospinal fluid (CSF) abnormalities in the form of elevated protein levels, and an elevated IgG index, and was given intravenous immunoglobulin followed by IV methylprednisolone. While symptoms such as paranoia improved and the patient was able to better organize thoughts after 5 days, other symptoms such as delusions and hyperreflexia persisted for at least 1 month before resolving, and some symptoms, such as lability, did not resolve before discharge.

Patient 2 had a history of motor tics and anxiety, but showed signs of insomnia, mood lability, impaired concentration, difficulty finding words, and problems completing homework following a SARS-CoV-2 infection. The patient’s father previously had been diagnosed with COVID-19 and the patient developed respiratory symptoms and fever; an IgG serology test later confirmed a SARS-CoV-2 infection. The patient went on to experience internal preoccupation, aggression, and suicidal ideation. The patients was treated with aripiprazole and risperidone, but did not respond, and was admitted to the hospital. As with patient 1, patient 2 had CSF abnormalities in the form of elevated protein levels, and responded to IV methylprednisolone, with working memory and bradyphrenia improving. However, the patient developed insomnia, extreme anxiety, suicidal ideation, aggression, and sadness after discharge, and was readmitted. The patient was treated with IV immunoglobulin, and discharged with quetiapine and lithium.

“Six months later, although improved from initial presentation, the patient required academic accommodations and continued to endorse forgetfulness and attention difficulties. The patient’s chronic tics and anxiety were unchanged,” Dr. Bartley and colleagues wrote.

Patient 3 had no psychiatric history but started to demonstrate “odd behavior, including repetitive behaviors, anorexia, and insomnia” following a SARS-CoV-2 infection. After being hospitalized, the patient showed signs of “ideomotor apraxia, abulia, disorganized behavior, agitation, and diffusely brisk reflexes” and had a high white blood cell count, creatine kinase level, and C-reactive protein level. CSF was also abnormal for this patient, with three unique oligoclonal bands identified. The patient was treated with lorazepam and olanzapine, did not receive immunotherapy, and was discharged without psychiatric medications after 4 days.

When the researchers performed testing on each of the three patients, they found intrathecal anti–SARS-CoV-2 IgG and immunostained mouse brain tissue, and “a diverse set of candidate autoantigens by human phage immunoprecipitation sequencing” in patient 1 and patient 2. In comparison, patient 3 “neither appreciably immunostained nor enriched candidates by human phage immunoprecipitation sequencing,” the researchers said.

“These data motivate a systematic study of humoral immunity in the CSF of pediatric patients with COVID-19 and neuropsychiatric involvement and the potential for immunotherapy in some,” Dr. Bartley and colleagues concluded.
 

Potential of CNS autoimmunity

Evan J. Kyzar, MD, PhD, a resident physician in psychiatry at New York State Psychiatric Institute in New York Presbyterian–Columbia Campus, said in an interview that the results of the case series show some pediatric patients with neuropsychiatric symptoms can have anti-SARS-CoV-2 antibodies after viral clearance.

“Interestingly, some of the patients in this study also had antibodies in the CSF that targeted native proteins, demonstrating that COVID-19 may lead to autoimmunity directed at the brain,” he said. “This study increases our knowledge of how COVID-19 interacts with the nervous system and how autoimmune mechanisms might be contributing to at least a portion of patients with neuropsychiatric symptoms during acute infection, and possibly even after viral clearance.”

Dr. Kyzar noted that the immunological methods in the study were “cutting-edge” and the validation exploring the immune responses was detailed, but was limited because of the small sample size.

“[T]he researchers are using similar techniques to explore psychiatric disorders such as depression and schizophrenia to determine if some patients diagnosed with these conditions may have CNS-targeting autoantibodies that contribute to their symptoms and clinical presentation,” Dr. Kyzar said. “This work has the potential to discover novel neuroimmune mechanisms contributing to neuropsychiatric disease and offer possible pathways for the discovery of new treatments.”

The authors reported financial relationships with Allen & Company, the Chan Zuckerberg Initiative, National Institutes of Health, Novartis, Public Health Company, Roche/Genentech, Sandler Foundation, and Takeda in the form of grants and personal fees. They reported funding and/or support from the Brain Research Foundation, Hanna H. Gray Fellowship, Howard Hughes Medical Institute, John A. Watson Scholar Program, Latinx Center of Excellence, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, President’s Postdoctoral Fellowship Program, and Shared Instrumentation grant. Dr. Kyzar reported no relevant financial disclosures.

Recent research suggests that some pediatric patients who develop neuropsychiatric symptoms from COVID-19 may have intrathecal antineural SARS-CoV-2 autoantibodies, which may hint at central nervous system (CNS) autoimmunity in these patients.

“Overall, these findings indicate that severe neuropsychiatric symptoms can occur in the setting of pediatric COVID-19, including patients who lack many of the cardinal systemic features,” Christopher M. Bartley, MD, PhD, of the Weill Institute for Neurosciences at the University of California, San Francisco, and colleagues wrote in their study. “These data highlight the possibility of SARS-CoV-2 neuroinvasion and/or CNS autoimmunity in pediatric patients with COVID-19 and neuropsychiatric symptoms.”

In a case series published Oct. 25 in JAMA Neurology (doi: 10.1001/jamaneurol.2021.3821), Dr. Bartley and colleagues examined three pediatric patients who were infected with SARS-CoV-2 and, over a period of 5 months in 2020, were admitted to the hospital – where they received a neurology consultation for “subacute, functionally impairing behavioral changes.”

Patient 1 had a history of unspecified anxiety and depression, and was admitted for erratic behavior, paranoia-like fears, social withdrawal, and insomnia. The patient did not respond to treatment with risperidone and gabapentin, and was readmitted soon after discharge, then treated with olanzapine followed by a transition to valproate and lorazepam. It was found the patient had cerebrospinal fluid (CSF) abnormalities in the form of elevated protein levels, and an elevated IgG index, and was given intravenous immunoglobulin followed by IV methylprednisolone. While symptoms such as paranoia improved and the patient was able to better organize thoughts after 5 days, other symptoms such as delusions and hyperreflexia persisted for at least 1 month before resolving, and some symptoms, such as lability, did not resolve before discharge.

Patient 2 had a history of motor tics and anxiety, but showed signs of insomnia, mood lability, impaired concentration, difficulty finding words, and problems completing homework following a SARS-CoV-2 infection. The patient’s father previously had been diagnosed with COVID-19 and the patient developed respiratory symptoms and fever; an IgG serology test later confirmed a SARS-CoV-2 infection. The patient went on to experience internal preoccupation, aggression, and suicidal ideation. The patients was treated with aripiprazole and risperidone, but did not respond, and was admitted to the hospital. As with patient 1, patient 2 had CSF abnormalities in the form of elevated protein levels, and responded to IV methylprednisolone, with working memory and bradyphrenia improving. However, the patient developed insomnia, extreme anxiety, suicidal ideation, aggression, and sadness after discharge, and was readmitted. The patient was treated with IV immunoglobulin, and discharged with quetiapine and lithium.

“Six months later, although improved from initial presentation, the patient required academic accommodations and continued to endorse forgetfulness and attention difficulties. The patient’s chronic tics and anxiety were unchanged,” Dr. Bartley and colleagues wrote.

Patient 3 had no psychiatric history but started to demonstrate “odd behavior, including repetitive behaviors, anorexia, and insomnia” following a SARS-CoV-2 infection. After being hospitalized, the patient showed signs of “ideomotor apraxia, abulia, disorganized behavior, agitation, and diffusely brisk reflexes” and had a high white blood cell count, creatine kinase level, and C-reactive protein level. CSF was also abnormal for this patient, with three unique oligoclonal bands identified. The patient was treated with lorazepam and olanzapine, did not receive immunotherapy, and was discharged without psychiatric medications after 4 days.

When the researchers performed testing on each of the three patients, they found intrathecal anti–SARS-CoV-2 IgG and immunostained mouse brain tissue, and “a diverse set of candidate autoantigens by human phage immunoprecipitation sequencing” in patient 1 and patient 2. In comparison, patient 3 “neither appreciably immunostained nor enriched candidates by human phage immunoprecipitation sequencing,” the researchers said.

“These data motivate a systematic study of humoral immunity in the CSF of pediatric patients with COVID-19 and neuropsychiatric involvement and the potential for immunotherapy in some,” Dr. Bartley and colleagues concluded.
 

Potential of CNS autoimmunity

Evan J. Kyzar, MD, PhD, a resident physician in psychiatry at New York State Psychiatric Institute in New York Presbyterian–Columbia Campus, said in an interview that the results of the case series show some pediatric patients with neuropsychiatric symptoms can have anti-SARS-CoV-2 antibodies after viral clearance.

“Interestingly, some of the patients in this study also had antibodies in the CSF that targeted native proteins, demonstrating that COVID-19 may lead to autoimmunity directed at the brain,” he said. “This study increases our knowledge of how COVID-19 interacts with the nervous system and how autoimmune mechanisms might be contributing to at least a portion of patients with neuropsychiatric symptoms during acute infection, and possibly even after viral clearance.”

Dr. Kyzar noted that the immunological methods in the study were “cutting-edge” and the validation exploring the immune responses was detailed, but was limited because of the small sample size.

“[T]he researchers are using similar techniques to explore psychiatric disorders such as depression and schizophrenia to determine if some patients diagnosed with these conditions may have CNS-targeting autoantibodies that contribute to their symptoms and clinical presentation,” Dr. Kyzar said. “This work has the potential to discover novel neuroimmune mechanisms contributing to neuropsychiatric disease and offer possible pathways for the discovery of new treatments.”

The authors reported financial relationships with Allen & Company, the Chan Zuckerberg Initiative, National Institutes of Health, Novartis, Public Health Company, Roche/Genentech, Sandler Foundation, and Takeda in the form of grants and personal fees. They reported funding and/or support from the Brain Research Foundation, Hanna H. Gray Fellowship, Howard Hughes Medical Institute, John A. Watson Scholar Program, Latinx Center of Excellence, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, President’s Postdoctoral Fellowship Program, and Shared Instrumentation grant. Dr. Kyzar reported no relevant financial disclosures.

Telehealth is safe and effective for the treatment of borderline personality disorder (BPD) and may even have an edge over in-person treatment, new research suggests.

Courtesy Dr. Mark Zimmerman

Investigators compared BPD outcomes with therapy delivered in person and via telemedicine and found comparable reductions in depression, anxiety, and anger symptoms as well as improved overall well-being and mental health.

The results also suggest a telehealth advantage with significantly better patient attendance vs. patients treated in-person.

“We found a large effect size of treatment in both groups, as well as comparable levels of satisfaction with treatment, symptom reduction, and improved functioning, coping ability, positive mental health, and general well-being,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., said in an interview.

The study was published online Nov. 8 in the Journal of Personality Disorders.
 

‘No other option’

Most previous research investigating telehealth has occurred in outpatient, individual treatment settings and has not examined telehealth-delivered group therapy or partial hospitalization, the authors noted.

“Until the pandemic, we were delivering care in person, but when the pandemic began, because of public safety recommendations, we knew that we could no longer continue doing so,” said Dr. Zimmerman, director of the outpatient division at the partial hospital program (PHP), Rhode Island Hospital.

“In switching to a telehealth platform, we were concerned about patient safety and acceptability of delivering care in that manner, especially with patients with BPD, which is associated with impulsive behavior, self-harm, and suicidal behavior, among other problems,” he said. However “we had no other option” than to utilize a telehealth delivery mode, since the alternative was to shut down the program.

The investigators were “interested in whether or not virtual treatment in an acute intensive setting, such as a PHP, would be as safe, acceptable, and effective as in-person treatment.”

The study was part of the ongoing work of the Rhode Island Methods to Improve Diagnostic Assessment and Services.
 

Additional safety measures

Treatment, consisting of an Acceptance and Commitment Therapy (ACT) treatment model – including intake assessments, individual therapy, psychiatric visits, and group therapy – was delivered by a multidisciplinary team via Zoom.

Dr. Zimmerman noted that the team implemented additional safety precautions, including having patients check in at the beginning of each day to indicate their location, not seeing patients who were out of state, and making sure all patients had a contact person.

In addition, beyond the therapist leading the group, another therapist was always available, overseeing groups and meeting one-on-one (virtually) with participants if they had been triggered by the group process and were highly distressed.

Patients were asked to complete a number of questionnaires, including the Clinically Useful Patient Satisfaction Scale (CUPSS) at the end of their intake session. The primary outcome measure was the Remission from Depression Questionnaire (RDQ-M).

The study was conducted between May 1 and Dec. 15 of 2020 and included 64 patients with BPD who were treated for the first time in the Rhode Island Hospital PHP. They were compared to 117 patients who participated in the in-person program during the same months in 2019.

Participant characteristics were similar – for example, three-quarters of the participants in both groups were female, and the mean age was 34 years.
 

‘Sea change’

Most patients in the telehealth and in-person groups reported being “very” or “extremely” satisfied with the initial evaluation (90% vs. 85.3%, c² = 0.74) and were hopeful that they would get better (85.8% vs. 82.1%, c² = 0.45).

Upon completion of the program, 100% of the in-person and 95.4% of the telehealth group indicated that they were “very” or “extremely” satisfied (c² = 4.62), and “under both telehealth and in-person treatment conditions, the patients significantly improved from admission to discharge on each of the RDQ-M subscales, with large effect sizes found for most of the subscales,” the authors reported.

There were significant differences between the groups in the average number of days of attendance and number of days missed.

A nonsignificantly higher proportion of patients completed the telehealth program, vs. the in-person program (68.8% vs. 59%, c² = 1.69).

In both programs, transfer to inpatient care and dissatisfaction-related withdrawal from the program were low (both < 2%). Notably, no patients attempted or completed suicide during treatment.

Virtual treatment is more convenient than in-person treatment, Dr. Zimmerman noted. “Some patients – generally those with medical or transportation issues – told us they otherwise would not have been able to participate [in the program] if treatment had been in person.”

He added, “My prediction is that 5 years from now, two-thirds to three-quarters of outpatient visits will be virtual because that is what the patients prefer – and although there will certainly be individuals who prefer in-person care, I think we’ve witnessed a sea change in how behavioral health care will be delivered.”
 

‘Game changer’

In an interview, Monica Carsky, PhD, clinical assistant professor of psychology in psychiatry and a senior fellow at the Personality Disorders Institute, Weill Cornell Medical College, New York, said the study has “a lot of valuable detail about how to set up a virtual PHP, which could guide any group wanting to try this.”

Dr. Carsky, who was not involved with the study, called it “a very important contribution to the research literature on efficacious treatment of BPD,” although it is not a randomized controlled trial.

“Adding more individual attention to the virtual group (e.g., having a co-host in the groups) seems as though it may be an important factor in dealing with the limitations of virtual treatment,” she noted.

However, she continued, “a limitation is that outcome assessment relied on self-administered questionnaires and did not include clinician rating scales, so the response may have been subject to the effects of social desirability bias.”

Courtesy Dr. Donald Black

Donald W. Black, MD, associate chief of staff for mental health at the Iowa City Veterans Administration Hospital, said in an interview that the pandemic has been a “game changer, as we have had to quickly adapt mental health programs to a virtual format.

“For the most part, they have been remarkably successful for a variety of conditions, and Zimmerman and colleagues now show this for BPD families,” said Dr. Black, who was not associated with the research.

No study funding was listed. The study authors, Dr. Carsky, and Dr. Black have disclosed no relevant financial relationships.
 

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

Telehealth is safe and effective for the treatment of borderline personality disorder (BPD) and may even have an edge over in-person treatment, new research suggests.

Courtesy Dr. Mark Zimmerman

Investigators compared BPD outcomes with therapy delivered in person and via telemedicine and found comparable reductions in depression, anxiety, and anger symptoms as well as improved overall well-being and mental health.

The results also suggest a telehealth advantage with significantly better patient attendance vs. patients treated in-person.

“We found a large effect size of treatment in both groups, as well as comparable levels of satisfaction with treatment, symptom reduction, and improved functioning, coping ability, positive mental health, and general well-being,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., said in an interview.

The study was published online Nov. 8 in the Journal of Personality Disorders.
 

‘No other option’

Most previous research investigating telehealth has occurred in outpatient, individual treatment settings and has not examined telehealth-delivered group therapy or partial hospitalization, the authors noted.

“Until the pandemic, we were delivering care in person, but when the pandemic began, because of public safety recommendations, we knew that we could no longer continue doing so,” said Dr. Zimmerman, director of the outpatient division at the partial hospital program (PHP), Rhode Island Hospital.

“In switching to a telehealth platform, we were concerned about patient safety and acceptability of delivering care in that manner, especially with patients with BPD, which is associated with impulsive behavior, self-harm, and suicidal behavior, among other problems,” he said. However “we had no other option” than to utilize a telehealth delivery mode, since the alternative was to shut down the program.

The investigators were “interested in whether or not virtual treatment in an acute intensive setting, such as a PHP, would be as safe, acceptable, and effective as in-person treatment.”

The study was part of the ongoing work of the Rhode Island Methods to Improve Diagnostic Assessment and Services.
 

Additional safety measures

Treatment, consisting of an Acceptance and Commitment Therapy (ACT) treatment model – including intake assessments, individual therapy, psychiatric visits, and group therapy – was delivered by a multidisciplinary team via Zoom.

Dr. Zimmerman noted that the team implemented additional safety precautions, including having patients check in at the beginning of each day to indicate their location, not seeing patients who were out of state, and making sure all patients had a contact person.

In addition, beyond the therapist leading the group, another therapist was always available, overseeing groups and meeting one-on-one (virtually) with participants if they had been triggered by the group process and were highly distressed.

Patients were asked to complete a number of questionnaires, including the Clinically Useful Patient Satisfaction Scale (CUPSS) at the end of their intake session. The primary outcome measure was the Remission from Depression Questionnaire (RDQ-M).

The study was conducted between May 1 and Dec. 15 of 2020 and included 64 patients with BPD who were treated for the first time in the Rhode Island Hospital PHP. They were compared to 117 patients who participated in the in-person program during the same months in 2019.

Participant characteristics were similar – for example, three-quarters of the participants in both groups were female, and the mean age was 34 years.
 

‘Sea change’

Most patients in the telehealth and in-person groups reported being “very” or “extremely” satisfied with the initial evaluation (90% vs. 85.3%, c² = 0.74) and were hopeful that they would get better (85.8% vs. 82.1%, c² = 0.45).

Upon completion of the program, 100% of the in-person and 95.4% of the telehealth group indicated that they were “very” or “extremely” satisfied (c² = 4.62), and “under both telehealth and in-person treatment conditions, the patients significantly improved from admission to discharge on each of the RDQ-M subscales, with large effect sizes found for most of the subscales,” the authors reported.

There were significant differences between the groups in the average number of days of attendance and number of days missed.

A nonsignificantly higher proportion of patients completed the telehealth program, vs. the in-person program (68.8% vs. 59%, c² = 1.69).

In both programs, transfer to inpatient care and dissatisfaction-related withdrawal from the program were low (both < 2%). Notably, no patients attempted or completed suicide during treatment.

Virtual treatment is more convenient than in-person treatment, Dr. Zimmerman noted. “Some patients – generally those with medical or transportation issues – told us they otherwise would not have been able to participate [in the program] if treatment had been in person.”

He added, “My prediction is that 5 years from now, two-thirds to three-quarters of outpatient visits will be virtual because that is what the patients prefer – and although there will certainly be individuals who prefer in-person care, I think we’ve witnessed a sea change in how behavioral health care will be delivered.”
 

‘Game changer’

In an interview, Monica Carsky, PhD, clinical assistant professor of psychology in psychiatry and a senior fellow at the Personality Disorders Institute, Weill Cornell Medical College, New York, said the study has “a lot of valuable detail about how to set up a virtual PHP, which could guide any group wanting to try this.”

Dr. Carsky, who was not involved with the study, called it “a very important contribution to the research literature on efficacious treatment of BPD,” although it is not a randomized controlled trial.

“Adding more individual attention to the virtual group (e.g., having a co-host in the groups) seems as though it may be an important factor in dealing with the limitations of virtual treatment,” she noted.

However, she continued, “a limitation is that outcome assessment relied on self-administered questionnaires and did not include clinician rating scales, so the response may have been subject to the effects of social desirability bias.”

Courtesy Dr. Donald Black

Donald W. Black, MD, associate chief of staff for mental health at the Iowa City Veterans Administration Hospital, said in an interview that the pandemic has been a “game changer, as we have had to quickly adapt mental health programs to a virtual format.

“For the most part, they have been remarkably successful for a variety of conditions, and Zimmerman and colleagues now show this for BPD families,” said Dr. Black, who was not associated with the research.

No study funding was listed. The study authors, Dr. Carsky, and Dr. Black have disclosed no relevant financial relationships.
 

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

Telehealth is safe and effective for the treatment of borderline personality disorder (BPD) and may even have an edge over in-person treatment, new research suggests.

Courtesy Dr. Mark Zimmerman

Investigators compared BPD outcomes with therapy delivered in person and via telemedicine and found comparable reductions in depression, anxiety, and anger symptoms as well as improved overall well-being and mental health.

The results also suggest a telehealth advantage with significantly better patient attendance vs. patients treated in-person.

“We found a large effect size of treatment in both groups, as well as comparable levels of satisfaction with treatment, symptom reduction, and improved functioning, coping ability, positive mental health, and general well-being,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., said in an interview.

The study was published online Nov. 8 in the Journal of Personality Disorders.
 

‘No other option’

Most previous research investigating telehealth has occurred in outpatient, individual treatment settings and has not examined telehealth-delivered group therapy or partial hospitalization, the authors noted.

“Until the pandemic, we were delivering care in person, but when the pandemic began, because of public safety recommendations, we knew that we could no longer continue doing so,” said Dr. Zimmerman, director of the outpatient division at the partial hospital program (PHP), Rhode Island Hospital.

“In switching to a telehealth platform, we were concerned about patient safety and acceptability of delivering care in that manner, especially with patients with BPD, which is associated with impulsive behavior, self-harm, and suicidal behavior, among other problems,” he said. However “we had no other option” than to utilize a telehealth delivery mode, since the alternative was to shut down the program.

The investigators were “interested in whether or not virtual treatment in an acute intensive setting, such as a PHP, would be as safe, acceptable, and effective as in-person treatment.”

The study was part of the ongoing work of the Rhode Island Methods to Improve Diagnostic Assessment and Services.
 

Additional safety measures

Treatment, consisting of an Acceptance and Commitment Therapy (ACT) treatment model – including intake assessments, individual therapy, psychiatric visits, and group therapy – was delivered by a multidisciplinary team via Zoom.

Dr. Zimmerman noted that the team implemented additional safety precautions, including having patients check in at the beginning of each day to indicate their location, not seeing patients who were out of state, and making sure all patients had a contact person.

In addition, beyond the therapist leading the group, another therapist was always available, overseeing groups and meeting one-on-one (virtually) with participants if they had been triggered by the group process and were highly distressed.

Patients were asked to complete a number of questionnaires, including the Clinically Useful Patient Satisfaction Scale (CUPSS) at the end of their intake session. The primary outcome measure was the Remission from Depression Questionnaire (RDQ-M).

The study was conducted between May 1 and Dec. 15 of 2020 and included 64 patients with BPD who were treated for the first time in the Rhode Island Hospital PHP. They were compared to 117 patients who participated in the in-person program during the same months in 2019.

Participant characteristics were similar – for example, three-quarters of the participants in both groups were female, and the mean age was 34 years.
 

‘Sea change’

Most patients in the telehealth and in-person groups reported being “very” or “extremely” satisfied with the initial evaluation (90% vs. 85.3%, c² = 0.74) and were hopeful that they would get better (85.8% vs. 82.1%, c² = 0.45).

Upon completion of the program, 100% of the in-person and 95.4% of the telehealth group indicated that they were “very” or “extremely” satisfied (c² = 4.62), and “under both telehealth and in-person treatment conditions, the patients significantly improved from admission to discharge on each of the RDQ-M subscales, with large effect sizes found for most of the subscales,” the authors reported.

There were significant differences between the groups in the average number of days of attendance and number of days missed.

A nonsignificantly higher proportion of patients completed the telehealth program, vs. the in-person program (68.8% vs. 59%, c² = 1.69).

In both programs, transfer to inpatient care and dissatisfaction-related withdrawal from the program were low (both < 2%). Notably, no patients attempted or completed suicide during treatment.

Virtual treatment is more convenient than in-person treatment, Dr. Zimmerman noted. “Some patients – generally those with medical or transportation issues – told us they otherwise would not have been able to participate [in the program] if treatment had been in person.”

He added, “My prediction is that 5 years from now, two-thirds to three-quarters of outpatient visits will be virtual because that is what the patients prefer – and although there will certainly be individuals who prefer in-person care, I think we’ve witnessed a sea change in how behavioral health care will be delivered.”
 

‘Game changer’

In an interview, Monica Carsky, PhD, clinical assistant professor of psychology in psychiatry and a senior fellow at the Personality Disorders Institute, Weill Cornell Medical College, New York, said the study has “a lot of valuable detail about how to set up a virtual PHP, which could guide any group wanting to try this.”

Dr. Carsky, who was not involved with the study, called it “a very important contribution to the research literature on efficacious treatment of BPD,” although it is not a randomized controlled trial.

“Adding more individual attention to the virtual group (e.g., having a co-host in the groups) seems as though it may be an important factor in dealing with the limitations of virtual treatment,” she noted.

However, she continued, “a limitation is that outcome assessment relied on self-administered questionnaires and did not include clinician rating scales, so the response may have been subject to the effects of social desirability bias.”

Courtesy Dr. Donald Black

Donald W. Black, MD, associate chief of staff for mental health at the Iowa City Veterans Administration Hospital, said in an interview that the pandemic has been a “game changer, as we have had to quickly adapt mental health programs to a virtual format.

“For the most part, they have been remarkably successful for a variety of conditions, and Zimmerman and colleagues now show this for BPD families,” said Dr. Black, who was not associated with the research.

No study funding was listed. The study authors, Dr. Carsky, and Dr. Black have disclosed no relevant financial relationships.
 

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

Brain beta rhythm predicts early and robust response to deep brain stimulation (DBS) for severe depression in new findings that could help optimize and personalize DBS treatment protocols, early research suggests.

In a small study, investigators found brief stimulation at the time of implantation of DBS leads induced a rapid and consistent decrease in beta power measured at the site of stimulation, which correlated with significant and sustained decrease in depressive symptoms.

“Patient by patient, the magnitude of the decrease in the left beta power could predict how well they were doing a week later,” study investigator Helen Mayberg, MD, founding director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai in New York, told this news organization.

The study was published online Nov. 3 in Translational Psychiatry.
 

Optimal targets identified

Eight adults with treatment-resistant depression underwent intraoperative electrophysiological recording at the time that bilateral DBS leads were implanted in the subcallosal cingulate (SCC).

Using patient-specific tractography models prior to surgery, the investigators identified the optimal target within the SCC for lead placement.

During surgery, 20 minutes of stimulation in the optimal tractography-defined targets was delivered, with no stimulation in the 4 weeks after surgery. Local field potentials (LFPs) – electrical signals between neurons deep in the brain – were simultaneously recorded during intraoperative stimulation.

One week after brief intraoperative stimulation, patient depression scores had declined by 45.6% on the 17-item Hamilton Depression Rating Scale (HDRS-17).

This early antidepressant response correlated with a decrease in the beta power recorded from the left hemisphere SCC. The correlation of symptom improvement with reduction in SCC beta power suggests that this electrophysiological finding is a “biomarker for treatment optimization,” the investigators note.

“This study shows reproducible and consistent changes in a brain readout over the first minutes of optimized stimulation in the operating room in individual patients,” Dr. Mayberg said in a press release.

“Within minutes of stimulation inside the operating room, there was a change in the beta brain rhythm. Patients who showed larger changes then experienced greater relief from their depression in the week after surgery,” added Allison Waters, PhD, a co–first author on the study and electrophysiology core leader at Mount Sinai’s Nash Center.

It appears that the early decline in depressive symptoms is “partially but not completely lost” during a postoperative, one-month washout period, the researchers note.

In addition, it remains unknown whether intraoperative stimulation-induced changes in beta power are predictive of eventual sustained clinical response to chronic therapeutic SCC DBS for treatment-resistant depression.

To this point, however, chronic SCC DBS at the tractography-defined “optimal” locations led to a response rate of 88% (7 of 8) after 6 months of treatment, they report.
 

One step closer to precision psychiatry

“This line of work is moving the field one step closer to precision psychiatry,” Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Massachusetts, said in an interview.

“Outside of psychiatry, many diseases have measurable biomarkers that correlate with whether the disease is present or its severity. For example, for diabetes there is hemoglobin A1c, and for multiple sclerosis, brain lesions on MRI are both diagnostic and prognostic. Sadly, within psychiatry, biomarkers are few and far between,” said Dr. Lakhan, who wasn’t involved in this study.

“Over the last decades, an interesting phenomenon occurs with DBS for patients with advanced Parkinson’s – often their depression abates and mood improves. Several lines of studies have tried to tease apart whether this was primarily from alleviating the motor symptoms of Parkinson’s or [if] DBS is directly implicated in mood enhancement. Lo and behold a subset of patients with treatment-resistant depression demonstrate improvement on standardized depression testing,” Dr. Lakhan added.

This study now shows that beta rhythm – a signal deep in the brain that traditional EEG can’t pick up – “predicted who would later benefit from DBS right at the time of implantation,” Dr. Lakhan said.

“This is incredibly important for not only predicting response to DBS for depression, but specifically targeting this potential biomarker (deep beta rhythm) in and outside of brain surgery,” he told this news organization.

“Other therapy trials, for instance, with drugs or non-invasive, digital neuroactivation and modulation (DiNaMo), may use this key biomarker to optimize its development and maximize effect, one day, for a given individual,” Dr. Lakhan predicted.

“The challenge remains that these signals are deep in the brain and currently require surgical implantation of electrodes for recordings. However, technologies such as magnetoencephalography (MEG) that use powerful external magnetics may substitute,” he added.

Funding support was provided by the National Institutes of Health, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, and the Hope for Depression Research Foundation. Implanted devices used in this research were donated by Medtronic. Dr. Mayberg receives consulting and licensing fees from Abbott Labs. Dr. Lakhan has disclosed no relevant financial relationships.

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

Brain beta rhythm predicts early and robust response to deep brain stimulation (DBS) for severe depression in new findings that could help optimize and personalize DBS treatment protocols, early research suggests.

In a small study, investigators found brief stimulation at the time of implantation of DBS leads induced a rapid and consistent decrease in beta power measured at the site of stimulation, which correlated with significant and sustained decrease in depressive symptoms.

“Patient by patient, the magnitude of the decrease in the left beta power could predict how well they were doing a week later,” study investigator Helen Mayberg, MD, founding director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai in New York, told this news organization.

The study was published online Nov. 3 in Translational Psychiatry.
 

Optimal targets identified

Eight adults with treatment-resistant depression underwent intraoperative electrophysiological recording at the time that bilateral DBS leads were implanted in the subcallosal cingulate (SCC).

Using patient-specific tractography models prior to surgery, the investigators identified the optimal target within the SCC for lead placement.

During surgery, 20 minutes of stimulation in the optimal tractography-defined targets was delivered, with no stimulation in the 4 weeks after surgery. Local field potentials (LFPs) – electrical signals between neurons deep in the brain – were simultaneously recorded during intraoperative stimulation.

One week after brief intraoperative stimulation, patient depression scores had declined by 45.6% on the 17-item Hamilton Depression Rating Scale (HDRS-17).

This early antidepressant response correlated with a decrease in the beta power recorded from the left hemisphere SCC. The correlation of symptom improvement with reduction in SCC beta power suggests that this electrophysiological finding is a “biomarker for treatment optimization,” the investigators note.

“This study shows reproducible and consistent changes in a brain readout over the first minutes of optimized stimulation in the operating room in individual patients,” Dr. Mayberg said in a press release.

“Within minutes of stimulation inside the operating room, there was a change in the beta brain rhythm. Patients who showed larger changes then experienced greater relief from their depression in the week after surgery,” added Allison Waters, PhD, a co–first author on the study and electrophysiology core leader at Mount Sinai’s Nash Center.

It appears that the early decline in depressive symptoms is “partially but not completely lost” during a postoperative, one-month washout period, the researchers note.

In addition, it remains unknown whether intraoperative stimulation-induced changes in beta power are predictive of eventual sustained clinical response to chronic therapeutic SCC DBS for treatment-resistant depression.

To this point, however, chronic SCC DBS at the tractography-defined “optimal” locations led to a response rate of 88% (7 of 8) after 6 months of treatment, they report.
 

One step closer to precision psychiatry

“This line of work is moving the field one step closer to precision psychiatry,” Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Massachusetts, said in an interview.

“Outside of psychiatry, many diseases have measurable biomarkers that correlate with whether the disease is present or its severity. For example, for diabetes there is hemoglobin A1c, and for multiple sclerosis, brain lesions on MRI are both diagnostic and prognostic. Sadly, within psychiatry, biomarkers are few and far between,” said Dr. Lakhan, who wasn’t involved in this study.

“Over the last decades, an interesting phenomenon occurs with DBS for patients with advanced Parkinson’s – often their depression abates and mood improves. Several lines of studies have tried to tease apart whether this was primarily from alleviating the motor symptoms of Parkinson’s or [if] DBS is directly implicated in mood enhancement. Lo and behold a subset of patients with treatment-resistant depression demonstrate improvement on standardized depression testing,” Dr. Lakhan added.

This study now shows that beta rhythm – a signal deep in the brain that traditional EEG can’t pick up – “predicted who would later benefit from DBS right at the time of implantation,” Dr. Lakhan said.

“This is incredibly important for not only predicting response to DBS for depression, but specifically targeting this potential biomarker (deep beta rhythm) in and outside of brain surgery,” he told this news organization.

“Other therapy trials, for instance, with drugs or non-invasive, digital neuroactivation and modulation (DiNaMo), may use this key biomarker to optimize its development and maximize effect, one day, for a given individual,” Dr. Lakhan predicted.

“The challenge remains that these signals are deep in the brain and currently require surgical implantation of electrodes for recordings. However, technologies such as magnetoencephalography (MEG) that use powerful external magnetics may substitute,” he added.

Funding support was provided by the National Institutes of Health, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, and the Hope for Depression Research Foundation. Implanted devices used in this research were donated by Medtronic. Dr. Mayberg receives consulting and licensing fees from Abbott Labs. Dr. Lakhan has disclosed no relevant financial relationships.

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

Brain beta rhythm predicts early and robust response to deep brain stimulation (DBS) for severe depression in new findings that could help optimize and personalize DBS treatment protocols, early research suggests.

In a small study, investigators found brief stimulation at the time of implantation of DBS leads induced a rapid and consistent decrease in beta power measured at the site of stimulation, which correlated with significant and sustained decrease in depressive symptoms.

“Patient by patient, the magnitude of the decrease in the left beta power could predict how well they were doing a week later,” study investigator Helen Mayberg, MD, founding director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai in New York, told this news organization.

The study was published online Nov. 3 in Translational Psychiatry.
 

Optimal targets identified

Eight adults with treatment-resistant depression underwent intraoperative electrophysiological recording at the time that bilateral DBS leads were implanted in the subcallosal cingulate (SCC).

Using patient-specific tractography models prior to surgery, the investigators identified the optimal target within the SCC for lead placement.

During surgery, 20 minutes of stimulation in the optimal tractography-defined targets was delivered, with no stimulation in the 4 weeks after surgery. Local field potentials (LFPs) – electrical signals between neurons deep in the brain – were simultaneously recorded during intraoperative stimulation.

One week after brief intraoperative stimulation, patient depression scores had declined by 45.6% on the 17-item Hamilton Depression Rating Scale (HDRS-17).

This early antidepressant response correlated with a decrease in the beta power recorded from the left hemisphere SCC. The correlation of symptom improvement with reduction in SCC beta power suggests that this electrophysiological finding is a “biomarker for treatment optimization,” the investigators note.

“This study shows reproducible and consistent changes in a brain readout over the first minutes of optimized stimulation in the operating room in individual patients,” Dr. Mayberg said in a press release.

“Within minutes of stimulation inside the operating room, there was a change in the beta brain rhythm. Patients who showed larger changes then experienced greater relief from their depression in the week after surgery,” added Allison Waters, PhD, a co–first author on the study and electrophysiology core leader at Mount Sinai’s Nash Center.

It appears that the early decline in depressive symptoms is “partially but not completely lost” during a postoperative, one-month washout period, the researchers note.

In addition, it remains unknown whether intraoperative stimulation-induced changes in beta power are predictive of eventual sustained clinical response to chronic therapeutic SCC DBS for treatment-resistant depression.

To this point, however, chronic SCC DBS at the tractography-defined “optimal” locations led to a response rate of 88% (7 of 8) after 6 months of treatment, they report.
 

One step closer to precision psychiatry

“This line of work is moving the field one step closer to precision psychiatry,” Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Massachusetts, said in an interview.

“Outside of psychiatry, many diseases have measurable biomarkers that correlate with whether the disease is present or its severity. For example, for diabetes there is hemoglobin A1c, and for multiple sclerosis, brain lesions on MRI are both diagnostic and prognostic. Sadly, within psychiatry, biomarkers are few and far between,” said Dr. Lakhan, who wasn’t involved in this study.

“Over the last decades, an interesting phenomenon occurs with DBS for patients with advanced Parkinson’s – often their depression abates and mood improves. Several lines of studies have tried to tease apart whether this was primarily from alleviating the motor symptoms of Parkinson’s or [if] DBS is directly implicated in mood enhancement. Lo and behold a subset of patients with treatment-resistant depression demonstrate improvement on standardized depression testing,” Dr. Lakhan added.

This study now shows that beta rhythm – a signal deep in the brain that traditional EEG can’t pick up – “predicted who would later benefit from DBS right at the time of implantation,” Dr. Lakhan said.

“This is incredibly important for not only predicting response to DBS for depression, but specifically targeting this potential biomarker (deep beta rhythm) in and outside of brain surgery,” he told this news organization.

“Other therapy trials, for instance, with drugs or non-invasive, digital neuroactivation and modulation (DiNaMo), may use this key biomarker to optimize its development and maximize effect, one day, for a given individual,” Dr. Lakhan predicted.

“The challenge remains that these signals are deep in the brain and currently require surgical implantation of electrodes for recordings. However, technologies such as magnetoencephalography (MEG) that use powerful external magnetics may substitute,” he added.

Funding support was provided by the National Institutes of Health, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, and the Hope for Depression Research Foundation. Implanted devices used in this research were donated by Medtronic. Dr. Mayberg receives consulting and licensing fees from Abbott Labs. Dr. Lakhan has disclosed no relevant financial relationships.

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

He always dressed the same at conferences: dark suit, white shirt, bright red bow tie.

Courtesy of Beck Institute for Cognitive Behavior Therapy

For all his fame, he was very kind, warmly greeting those who wanted to see him and immediately turning attention toward their research rather than his own. Aaron Beck actually didn’t lecture much; he preferred to roleplay cognitive therapy with an audience member acting as the patient. He would engage in what he called Socratic questioning, or more formally, cognitive restructuring, with warmth and true curiosity:

• What might be another explanation or viewpoint?
• What are the effects of thinking this way?
• Can you think of any evidence that supports the opposite view?

The audience member/patient would benefit not only from thinking about things differently, but also from the captivating interaction with the man, Aaron Temkin Beck, MD, (who went by Tim), youngest child of Jewish immigrants from the Ukraine.

When written up in treatment manuals, cognitive restructuring can seem cold and overly logical, but in person, Dr. Beck made it come to life. This ability to nurture curiosity was a special talent; his friend and fellow cognitive psychologist Donald Meichenbaum, PhD, recalls that even over lunch, he never stopped asking questions, personal and professional, on a wide range of topics.

It is widely accepted that Dr. Beck, who died Nov. 1 at the age of 100 in suburban Philadelphia, was the most important figure in the field of cognitive-behavioral therapy (CBT).

He didn’t invent the field. Behaviorism predated him by generations, founded by figures such as John Watson and B.F. Skinner. Those psychologists set up behaviorism as an alternative to the reigning power of Freudian psychoanalysis, but they ran a distant second.

It wasn’t until Dr. Beck added a new approach, cognitive therapy, to the behavioristic movement that the new mélange, CBT, began to gain traction with clinicians and researchers. Dr. Beck, who had trained in psychiatry, developed his ideas in the 1960s while observing what he believed were limitations in the classic Freudian methods. He recognized that patients had “automatic thoughts,” not just unconscious emotions, when they engaged in Freudian free association, saying whatever came to their minds.

These thoughts often distorted reality, he observed; they were “maladaptive beliefs,” and when they changed, patients’ emotional states improved.

Dr. Beck wasn’t alone. The psychologist Albert Ellis, PhD, in New York, had come to similar conclusions a decade earlier, though with a more coldly logical and challenging style. The prominent British psychologist Hans Eysenck, PhD, had argued strongly that Freudian psychoanalysis was ineffective and that behavioral approaches were better.

Dr. Beck turned the Freudian equation around: Instead of emotion as cause and thought as effect, it was thought which affected emotion, for better or worse. Once you connected behavior as the outcome, you had the essence of CBT: thought, emotion, and behavior – each affecting the other, with thought being the strongest axis of change.

The process wasn’t bloodless. Behaviorists defended their turf against cognitivists, just as much as Freudians rejected both. At one point the behaviorists in the Association for the Advancement of Behavior Therapy tried to expel the advocates of a cognitive approach. Dr. Beck responded by leading the cognitivists in creating a new journal; he emphasized the importance of research being the main mechanism to decide what treatments worked the best.

Putting these ideas out in the 1960s and 1970s, Dr. Beck garnered support from researchers when he manualized the approach. Freudian psychoanalysis was idiosyncratic; it was almost impossible to study empirically, because the therapist would be responding to the unpredictable dreams and memories of patients engaged in free association. Each case was unique.

But CBT was systematic: The same general approach was taken to all patients; the same negative cognitions were found in depression, for instance, like all-or-nothing thinking or overgeneralization. Once manualized, CBT became the standard method of psychotherapy studied with the newly developed method of randomized controlled trials (RCTs).

By the 1980s, RCTs had proven the efficacy of CBT in depression, and the approach took off.

Dr. Beck already had developed a series of rating scales: the Beck Depression Inventory, the Beck Scale for Suicidal Ideation, the Beck Anxiety Inventory, the Beck Hopelessness Scale. Widely used, these scales extended his influence enormously. Copyrighted, they created a new industry of psychological research.

Dr. Beck’s own work was mainly in depression, but his followers extended it everywhere else: anxiety disorders and phobias, eating disorders, substance abuse, bipolar illness, even schizophrenia. Meanwhile, Freudian psychoanalysis fell into a steep decline from which it never recovered.

Dr. Beck’s CBT became king of the hill in psychotherapy, but it wasn’t without criticism.

Some argued that it was abetted by insurance restrictions on psychotherapy, which favored shorter-term CBT; others that its research was biased in its favor because psychotherapy treatments, unlike medications, cannot be blinded; others that its efficacy could not be shown to be specific to its theory, as opposed to the interpersonal relationship between therapist and client.

Still, CBT has transformed psychotherapy and continues to expand its influence. Computer-based CBT has been proven effective, and digital CBT has become a standard approach in many smartphone applications and is central to the claims of multiple new biotechnology companies advocating for digital psychotherapy.

Aaron Beck continued publishing scientific articles to age 98. His last papers reviewed his life’s work. He characteristically gave credit to others, calmly recollected how he traveled away from psychoanalysis, described how his work started and ended in schizophrenia, and noted that the “working relationship with the therapist” remained a key factor for the success of CBT.

That parting comment reminds us that behind all the technology and research stands the kindly man in the dark suit, white shirt, and bright red bow tie, looking at you warmly, asking about your thoughts, and curiously wondering what might be another explanation or viewpoint you hadn’t considered.
 

Nassir Ghaemi, MD, MPH, is a professor of psychiatry at Tufts Medical Center and a lecturer in psychiatry at Harvard Medical School. He is the author of several general-interest books on psychiatry. A version of this article first appeared on Medscape.com.

He always dressed the same at conferences: dark suit, white shirt, bright red bow tie.

Courtesy of Beck Institute for Cognitive Behavior Therapy

For all his fame, he was very kind, warmly greeting those who wanted to see him and immediately turning attention toward their research rather than his own. Aaron Beck actually didn’t lecture much; he preferred to roleplay cognitive therapy with an audience member acting as the patient. He would engage in what he called Socratic questioning, or more formally, cognitive restructuring, with warmth and true curiosity:

• What might be another explanation or viewpoint?
• What are the effects of thinking this way?
• Can you think of any evidence that supports the opposite view?

The audience member/patient would benefit not only from thinking about things differently, but also from the captivating interaction with the man, Aaron Temkin Beck, MD, (who went by Tim), youngest child of Jewish immigrants from the Ukraine.

When written up in treatment manuals, cognitive restructuring can seem cold and overly logical, but in person, Dr. Beck made it come to life. This ability to nurture curiosity was a special talent; his friend and fellow cognitive psychologist Donald Meichenbaum, PhD, recalls that even over lunch, he never stopped asking questions, personal and professional, on a wide range of topics.

It is widely accepted that Dr. Beck, who died Nov. 1 at the age of 100 in suburban Philadelphia, was the most important figure in the field of cognitive-behavioral therapy (CBT).

He didn’t invent the field. Behaviorism predated him by generations, founded by figures such as John Watson and B.F. Skinner. Those psychologists set up behaviorism as an alternative to the reigning power of Freudian psychoanalysis, but they ran a distant second.

It wasn’t until Dr. Beck added a new approach, cognitive therapy, to the behavioristic movement that the new mélange, CBT, began to gain traction with clinicians and researchers. Dr. Beck, who had trained in psychiatry, developed his ideas in the 1960s while observing what he believed were limitations in the classic Freudian methods. He recognized that patients had “automatic thoughts,” not just unconscious emotions, when they engaged in Freudian free association, saying whatever came to their minds.

These thoughts often distorted reality, he observed; they were “maladaptive beliefs,” and when they changed, patients’ emotional states improved.

Dr. Beck wasn’t alone. The psychologist Albert Ellis, PhD, in New York, had come to similar conclusions a decade earlier, though with a more coldly logical and challenging style. The prominent British psychologist Hans Eysenck, PhD, had argued strongly that Freudian psychoanalysis was ineffective and that behavioral approaches were better.

Dr. Beck turned the Freudian equation around: Instead of emotion as cause and thought as effect, it was thought which affected emotion, for better or worse. Once you connected behavior as the outcome, you had the essence of CBT: thought, emotion, and behavior – each affecting the other, with thought being the strongest axis of change.

The process wasn’t bloodless. Behaviorists defended their turf against cognitivists, just as much as Freudians rejected both. At one point the behaviorists in the Association for the Advancement of Behavior Therapy tried to expel the advocates of a cognitive approach. Dr. Beck responded by leading the cognitivists in creating a new journal; he emphasized the importance of research being the main mechanism to decide what treatments worked the best.

Putting these ideas out in the 1960s and 1970s, Dr. Beck garnered support from researchers when he manualized the approach. Freudian psychoanalysis was idiosyncratic; it was almost impossible to study empirically, because the therapist would be responding to the unpredictable dreams and memories of patients engaged in free association. Each case was unique.

But CBT was systematic: The same general approach was taken to all patients; the same negative cognitions were found in depression, for instance, like all-or-nothing thinking or overgeneralization. Once manualized, CBT became the standard method of psychotherapy studied with the newly developed method of randomized controlled trials (RCTs).

By the 1980s, RCTs had proven the efficacy of CBT in depression, and the approach took off.

Dr. Beck already had developed a series of rating scales: the Beck Depression Inventory, the Beck Scale for Suicidal Ideation, the Beck Anxiety Inventory, the Beck Hopelessness Scale. Widely used, these scales extended his influence enormously. Copyrighted, they created a new industry of psychological research.

Dr. Beck’s own work was mainly in depression, but his followers extended it everywhere else: anxiety disorders and phobias, eating disorders, substance abuse, bipolar illness, even schizophrenia. Meanwhile, Freudian psychoanalysis fell into a steep decline from which it never recovered.

Dr. Beck’s CBT became king of the hill in psychotherapy, but it wasn’t without criticism.

Some argued that it was abetted by insurance restrictions on psychotherapy, which favored shorter-term CBT; others that its research was biased in its favor because psychotherapy treatments, unlike medications, cannot be blinded; others that its efficacy could not be shown to be specific to its theory, as opposed to the interpersonal relationship between therapist and client.

Still, CBT has transformed psychotherapy and continues to expand its influence. Computer-based CBT has been proven effective, and digital CBT has become a standard approach in many smartphone applications and is central to the claims of multiple new biotechnology companies advocating for digital psychotherapy.

Aaron Beck continued publishing scientific articles to age 98. His last papers reviewed his life’s work. He characteristically gave credit to others, calmly recollected how he traveled away from psychoanalysis, described how his work started and ended in schizophrenia, and noted that the “working relationship with the therapist” remained a key factor for the success of CBT.

That parting comment reminds us that behind all the technology and research stands the kindly man in the dark suit, white shirt, and bright red bow tie, looking at you warmly, asking about your thoughts, and curiously wondering what might be another explanation or viewpoint you hadn’t considered.
 

Nassir Ghaemi, MD, MPH, is a professor of psychiatry at Tufts Medical Center and a lecturer in psychiatry at Harvard Medical School. He is the author of several general-interest books on psychiatry. A version of this article first appeared on Medscape.com.

He always dressed the same at conferences: dark suit, white shirt, bright red bow tie.

Courtesy of Beck Institute for Cognitive Behavior Therapy

For all his fame, he was very kind, warmly greeting those who wanted to see him and immediately turning attention toward their research rather than his own. Aaron Beck actually didn’t lecture much; he preferred to roleplay cognitive therapy with an audience member acting as the patient. He would engage in what he called Socratic questioning, or more formally, cognitive restructuring, with warmth and true curiosity:

• What might be another explanation or viewpoint?
• What are the effects of thinking this way?
• Can you think of any evidence that supports the opposite view?

The audience member/patient would benefit not only from thinking about things differently, but also from the captivating interaction with the man, Aaron Temkin Beck, MD, (who went by Tim), youngest child of Jewish immigrants from the Ukraine.

When written up in treatment manuals, cognitive restructuring can seem cold and overly logical, but in person, Dr. Beck made it come to life. This ability to nurture curiosity was a special talent; his friend and fellow cognitive psychologist Donald Meichenbaum, PhD, recalls that even over lunch, he never stopped asking questions, personal and professional, on a wide range of topics.

It is widely accepted that Dr. Beck, who died Nov. 1 at the age of 100 in suburban Philadelphia, was the most important figure in the field of cognitive-behavioral therapy (CBT).

He didn’t invent the field. Behaviorism predated him by generations, founded by figures such as John Watson and B.F. Skinner. Those psychologists set up behaviorism as an alternative to the reigning power of Freudian psychoanalysis, but they ran a distant second.

It wasn’t until Dr. Beck added a new approach, cognitive therapy, to the behavioristic movement that the new mélange, CBT, began to gain traction with clinicians and researchers. Dr. Beck, who had trained in psychiatry, developed his ideas in the 1960s while observing what he believed were limitations in the classic Freudian methods. He recognized that patients had “automatic thoughts,” not just unconscious emotions, when they engaged in Freudian free association, saying whatever came to their minds.

These thoughts often distorted reality, he observed; they were “maladaptive beliefs,” and when they changed, patients’ emotional states improved.

Dr. Beck wasn’t alone. The psychologist Albert Ellis, PhD, in New York, had come to similar conclusions a decade earlier, though with a more coldly logical and challenging style. The prominent British psychologist Hans Eysenck, PhD, had argued strongly that Freudian psychoanalysis was ineffective and that behavioral approaches were better.

Dr. Beck turned the Freudian equation around: Instead of emotion as cause and thought as effect, it was thought which affected emotion, for better or worse. Once you connected behavior as the outcome, you had the essence of CBT: thought, emotion, and behavior – each affecting the other, with thought being the strongest axis of change.

The process wasn’t bloodless. Behaviorists defended their turf against cognitivists, just as much as Freudians rejected both. At one point the behaviorists in the Association for the Advancement of Behavior Therapy tried to expel the advocates of a cognitive approach. Dr. Beck responded by leading the cognitivists in creating a new journal; he emphasized the importance of research being the main mechanism to decide what treatments worked the best.

Putting these ideas out in the 1960s and 1970s, Dr. Beck garnered support from researchers when he manualized the approach. Freudian psychoanalysis was idiosyncratic; it was almost impossible to study empirically, because the therapist would be responding to the unpredictable dreams and memories of patients engaged in free association. Each case was unique.

But CBT was systematic: The same general approach was taken to all patients; the same negative cognitions were found in depression, for instance, like all-or-nothing thinking or overgeneralization. Once manualized, CBT became the standard method of psychotherapy studied with the newly developed method of randomized controlled trials (RCTs).

By the 1980s, RCTs had proven the efficacy of CBT in depression, and the approach took off.

Dr. Beck already had developed a series of rating scales: the Beck Depression Inventory, the Beck Scale for Suicidal Ideation, the Beck Anxiety Inventory, the Beck Hopelessness Scale. Widely used, these scales extended his influence enormously. Copyrighted, they created a new industry of psychological research.

Dr. Beck’s own work was mainly in depression, but his followers extended it everywhere else: anxiety disorders and phobias, eating disorders, substance abuse, bipolar illness, even schizophrenia. Meanwhile, Freudian psychoanalysis fell into a steep decline from which it never recovered.

Dr. Beck’s CBT became king of the hill in psychotherapy, but it wasn’t without criticism.

Some argued that it was abetted by insurance restrictions on psychotherapy, which favored shorter-term CBT; others that its research was biased in its favor because psychotherapy treatments, unlike medications, cannot be blinded; others that its efficacy could not be shown to be specific to its theory, as opposed to the interpersonal relationship between therapist and client.

Still, CBT has transformed psychotherapy and continues to expand its influence. Computer-based CBT has been proven effective, and digital CBT has become a standard approach in many smartphone applications and is central to the claims of multiple new biotechnology companies advocating for digital psychotherapy.

Aaron Beck continued publishing scientific articles to age 98. His last papers reviewed his life’s work. He characteristically gave credit to others, calmly recollected how he traveled away from psychoanalysis, described how his work started and ended in schizophrenia, and noted that the “working relationship with the therapist” remained a key factor for the success of CBT.

That parting comment reminds us that behind all the technology and research stands the kindly man in the dark suit, white shirt, and bright red bow tie, looking at you warmly, asking about your thoughts, and curiously wondering what might be another explanation or viewpoint you hadn’t considered.
 

Nassir Ghaemi, MD, MPH, is a professor of psychiatry at Tufts Medical Center and a lecturer in psychiatry at Harvard Medical School. He is the author of several general-interest books on psychiatry. A version of this article first appeared on Medscape.com.

A newly discovered vascular brain barrier that blocks the passage of inflammatory molecules triggered by gut bacteria may be why patients with inflammatory bowel disease (IBD) are at increased risk for certain mental health disorders, including anxiety and depression, early research suggests.

The discovery, which was based on a preclinical model, could lead to new therapeutic targets that could have applications for both gastrointestinal and psychiatric conditions, investigators note.

The research team, which was led by immunologist Maria Rescigno, PhD, and neuroscientist Simona Lodato, PhD, both from Humanitas University, Milan, notes that the barrier resides in the choroid plexus, a region of the brain that is involved in filtering cerebrospinal fluid. The researchers found that the region closes in response to inflammatory molecules produced in reaction to the presence of intestinal bacteria in patients with gut disorders.

Dr. Lodato said in an interview that the brain’s choroid plexus vascular barrier, along with another barrier between the gut and liver, known as the gut vascular barrier, appear to control the movement of molecules along the gut-brain axis.

“We show that in addition to the epithelial barrier in the choroid plexus, there is a functional vascular barrier that only becomes evident in blocking entry of various inflammatory molecules under conditions of systemic inflammation,” Dr. Lodato said.

“This interruption of the gut-brain interaction has developed to protect the brain from inflammation. Why this happens is not yet known, but it is likely to prevent epileptic seizures and imbalanced neuronal activity,” added Dr. Rescigno.

The study was published online October 22 in Science.
 

The gut a root cause of mental illness?

Nearly 40% of patients with IBD also experience depression and anxiety. It was once thought that these conditions arose because of patients’ difficulties in coping with their disease, said Dr. Rescigno.

“People with these disorders conventionally thought to be caused by an imbalance in the brain may actually find the root cause is located in the intestine. This is the first time these symptoms have been associated with the choroid plexus vascular brain barrier and its closure,” she noted.

Dr. Rescigno added that subtle, rather than overt, inflammation may be all that’s required for closure of the choroid plexus and the subsequent effects on mental health.

In 2015, Dr. Rescigno’s group first described the gut vascular barrier that protects the systemic circulation from gut bacteria or associated bacteria-derived molecules. During intestinal inflammation, such as occurs in IBD, this barrier is compromised and becomes more permeable. This allows microbes to pass across the epithelium of the gut barrier and enter the systemic circulation, including the liver and spleen, explained Dr. Rescigno.

Dr. Rescigno and Dr. Lodato then explored whether this systemic inflammatory condition was connected to the brain along a gut-brain axis and found that it was.

The researchers tested the hypothesis that central nervous system symptoms may be due to vascular changes at the interface between the gut or the brain and elsewhere in the body.

“We set out to test whether opening of the gut vascular barrier would allow gut bacteria to trigger the release of inflammatory molecules that spread to more distant areas, possibly leading to a deficiency of certain nutrients and precipitating mental disorders,” they said.

An experimental preclinical model of the choroid plexus vascular barrier closure led to anxiety-like behavior, as well as short-term memory loss. That this behavior occurred independently of inflammation suggested that it was likely a response to closure itself, they note.

In the noninflammatory state, the epithelium of the choroid plexus filters molecules. Those that are ≤70 kDa are allowed to pass through to the brain. However, the investigators found that during systemic inflammation, this filtration stops, and the blood capillaries of the choroid plexus prevent entry of inflammatory molecules such as cytokines.

Dr. Lodato speculated that when the vascular barrier of the choroid plexus shuts off during the systemic inflammatory state, it responds by bathing the brain in cerebrospinal fluid.

“When the choroid plexus closes, like a door slamming shut, then communication between the brain and the rest of the body is halted. This means that the brain is deprived of certain nutrients and other beneficial molecules that usually enter via the cerebrospinal fluid or enriched of potentially dangerous ones, as drainage could also be affected,” she said.

If confirmed in further studies, these results may open the way to new interventions.
 

‘A significant leap forward’

Commenting on the findings, David T. Rubin, MD, professor of medicine at the University of Chicago, noted that the study’s results represent “a significant leap forward” and that it highlights “another important cost to uncontrolled gut inflammation that is the potential for worsened mental health disorders.”

Dr. Rubin, whose research involves measuring metabolites of the dietary amino acid tryptophan, including melatonin and serotonin, in patients with IBD, added that the findings offer a possible explanation for the association of both Crohn’s disease and ulcerative colitis with anxiety and depressive disorders.

“There was a belief that the association was in the opposite direction, that the mental health disorder was causing or worsening the gut inflammation, but this has been disavowed,” Dr. Rubin said.

“Most recently, the recognition that the major sources of serotonin and other metabolites of tryptophan that come from the gut microbiome has led to the hypothesis that the inflamed bowel and dysbiotic gut biome may in fact be driving the mental health disorders due to the effect of neurotransmitter imbalance,” he added. Dr. Rubin also suggested that the shutdown of the choroid plexus vascular barrier may contribute to this imbalance but that this needs additional study.

“This further supports my ongoing contention that the gut really is the center of the universe,” said Dr. Rubin.

Also commenting on the findings, Miguel Rigueiro, MD, professor in the department of medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, said, “There’s an implication that anxiety and depression and other behavioral health disorders may be explained by this mechanism. If that is the case, there may be a way to target medications against the choroid plexus and potentially treat depression or anxiety.”

This prospect was echoed by Dr. Rubin, who said, “The clinical implication is that treatment of gut inflammation may restore a balance to the neurotransmitters and resolve anxiety or depressive disorders.”

To identify new therapeutic targets, investigators will study the regions and circuits of the brain that are more susceptible to this closure of the choroid plexus, said Dr. Lodato.

“If these regions are associated with depression or other psychosocial disorders, then this new understanding around the choroid plexus vascular barrier might eventually have implications for helping treat such disorders,” she noted.

Reflecting a general shift from a brain-centric view of some psychosocial disorders to an intestinal-centric one, Dr. Lodato added, “The brain cannot be considered in isolation. It is part of a much larger body, and we need to think this way.”

Dr. Rescigno, Dr. Lodato, and Dr. Rubin report no relevant financial relationships. Dr. Rigueiro has served on advisory boards and as consultant for AbbVie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, SpA, and Bristol-Meyer Squibb.

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

A newly discovered vascular brain barrier that blocks the passage of inflammatory molecules triggered by gut bacteria may be why patients with inflammatory bowel disease (IBD) are at increased risk for certain mental health disorders, including anxiety and depression, early research suggests.

The discovery, which was based on a preclinical model, could lead to new therapeutic targets that could have applications for both gastrointestinal and psychiatric conditions, investigators note.

The research team, which was led by immunologist Maria Rescigno, PhD, and neuroscientist Simona Lodato, PhD, both from Humanitas University, Milan, notes that the barrier resides in the choroid plexus, a region of the brain that is involved in filtering cerebrospinal fluid. The researchers found that the region closes in response to inflammatory molecules produced in reaction to the presence of intestinal bacteria in patients with gut disorders.

Dr. Lodato said in an interview that the brain’s choroid plexus vascular barrier, along with another barrier between the gut and liver, known as the gut vascular barrier, appear to control the movement of molecules along the gut-brain axis.

“We show that in addition to the epithelial barrier in the choroid plexus, there is a functional vascular barrier that only becomes evident in blocking entry of various inflammatory molecules under conditions of systemic inflammation,” Dr. Lodato said.

“This interruption of the gut-brain interaction has developed to protect the brain from inflammation. Why this happens is not yet known, but it is likely to prevent epileptic seizures and imbalanced neuronal activity,” added Dr. Rescigno.

The study was published online October 22 in Science.
 

The gut a root cause of mental illness?

Nearly 40% of patients with IBD also experience depression and anxiety. It was once thought that these conditions arose because of patients’ difficulties in coping with their disease, said Dr. Rescigno.

“People with these disorders conventionally thought to be caused by an imbalance in the brain may actually find the root cause is located in the intestine. This is the first time these symptoms have been associated with the choroid plexus vascular brain barrier and its closure,” she noted.

Dr. Rescigno added that subtle, rather than overt, inflammation may be all that’s required for closure of the choroid plexus and the subsequent effects on mental health.

In 2015, Dr. Rescigno’s group first described the gut vascular barrier that protects the systemic circulation from gut bacteria or associated bacteria-derived molecules. During intestinal inflammation, such as occurs in IBD, this barrier is compromised and becomes more permeable. This allows microbes to pass across the epithelium of the gut barrier and enter the systemic circulation, including the liver and spleen, explained Dr. Rescigno.

Dr. Rescigno and Dr. Lodato then explored whether this systemic inflammatory condition was connected to the brain along a gut-brain axis and found that it was.

The researchers tested the hypothesis that central nervous system symptoms may be due to vascular changes at the interface between the gut or the brain and elsewhere in the body.

“We set out to test whether opening of the gut vascular barrier would allow gut bacteria to trigger the release of inflammatory molecules that spread to more distant areas, possibly leading to a deficiency of certain nutrients and precipitating mental disorders,” they said.

An experimental preclinical model of the choroid plexus vascular barrier closure led to anxiety-like behavior, as well as short-term memory loss. That this behavior occurred independently of inflammation suggested that it was likely a response to closure itself, they note.

In the noninflammatory state, the epithelium of the choroid plexus filters molecules. Those that are ≤70 kDa are allowed to pass through to the brain. However, the investigators found that during systemic inflammation, this filtration stops, and the blood capillaries of the choroid plexus prevent entry of inflammatory molecules such as cytokines.

Dr. Lodato speculated that when the vascular barrier of the choroid plexus shuts off during the systemic inflammatory state, it responds by bathing the brain in cerebrospinal fluid.

“When the choroid plexus closes, like a door slamming shut, then communication between the brain and the rest of the body is halted. This means that the brain is deprived of certain nutrients and other beneficial molecules that usually enter via the cerebrospinal fluid or enriched of potentially dangerous ones, as drainage could also be affected,” she said.

If confirmed in further studies, these results may open the way to new interventions.
 

‘A significant leap forward’

Commenting on the findings, David T. Rubin, MD, professor of medicine at the University of Chicago, noted that the study’s results represent “a significant leap forward” and that it highlights “another important cost to uncontrolled gut inflammation that is the potential for worsened mental health disorders.”

Dr. Rubin, whose research involves measuring metabolites of the dietary amino acid tryptophan, including melatonin and serotonin, in patients with IBD, added that the findings offer a possible explanation for the association of both Crohn’s disease and ulcerative colitis with anxiety and depressive disorders.

“There was a belief that the association was in the opposite direction, that the mental health disorder was causing or worsening the gut inflammation, but this has been disavowed,” Dr. Rubin said.

“Most recently, the recognition that the major sources of serotonin and other metabolites of tryptophan that come from the gut microbiome has led to the hypothesis that the inflamed bowel and dysbiotic gut biome may in fact be driving the mental health disorders due to the effect of neurotransmitter imbalance,” he added. Dr. Rubin also suggested that the shutdown of the choroid plexus vascular barrier may contribute to this imbalance but that this needs additional study.

“This further supports my ongoing contention that the gut really is the center of the universe,” said Dr. Rubin.

Also commenting on the findings, Miguel Rigueiro, MD, professor in the department of medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, said, “There’s an implication that anxiety and depression and other behavioral health disorders may be explained by this mechanism. If that is the case, there may be a way to target medications against the choroid plexus and potentially treat depression or anxiety.”

This prospect was echoed by Dr. Rubin, who said, “The clinical implication is that treatment of gut inflammation may restore a balance to the neurotransmitters and resolve anxiety or depressive disorders.”

To identify new therapeutic targets, investigators will study the regions and circuits of the brain that are more susceptible to this closure of the choroid plexus, said Dr. Lodato.

“If these regions are associated with depression or other psychosocial disorders, then this new understanding around the choroid plexus vascular barrier might eventually have implications for helping treat such disorders,” she noted.

Reflecting a general shift from a brain-centric view of some psychosocial disorders to an intestinal-centric one, Dr. Lodato added, “The brain cannot be considered in isolation. It is part of a much larger body, and we need to think this way.”

Dr. Rescigno, Dr. Lodato, and Dr. Rubin report no relevant financial relationships. Dr. Rigueiro has served on advisory boards and as consultant for AbbVie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, SpA, and Bristol-Meyer Squibb.

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

A newly discovered vascular brain barrier that blocks the passage of inflammatory molecules triggered by gut bacteria may be why patients with inflammatory bowel disease (IBD) are at increased risk for certain mental health disorders, including anxiety and depression, early research suggests.

The discovery, which was based on a preclinical model, could lead to new therapeutic targets that could have applications for both gastrointestinal and psychiatric conditions, investigators note.

The research team, which was led by immunologist Maria Rescigno, PhD, and neuroscientist Simona Lodato, PhD, both from Humanitas University, Milan, notes that the barrier resides in the choroid plexus, a region of the brain that is involved in filtering cerebrospinal fluid. The researchers found that the region closes in response to inflammatory molecules produced in reaction to the presence of intestinal bacteria in patients with gut disorders.

Dr. Lodato said in an interview that the brain’s choroid plexus vascular barrier, along with another barrier between the gut and liver, known as the gut vascular barrier, appear to control the movement of molecules along the gut-brain axis.

“We show that in addition to the epithelial barrier in the choroid plexus, there is a functional vascular barrier that only becomes evident in blocking entry of various inflammatory molecules under conditions of systemic inflammation,” Dr. Lodato said.

“This interruption of the gut-brain interaction has developed to protect the brain from inflammation. Why this happens is not yet known, but it is likely to prevent epileptic seizures and imbalanced neuronal activity,” added Dr. Rescigno.

The study was published online October 22 in Science.
 

The gut a root cause of mental illness?

Nearly 40% of patients with IBD also experience depression and anxiety. It was once thought that these conditions arose because of patients’ difficulties in coping with their disease, said Dr. Rescigno.

“People with these disorders conventionally thought to be caused by an imbalance in the brain may actually find the root cause is located in the intestine. This is the first time these symptoms have been associated with the choroid plexus vascular brain barrier and its closure,” she noted.

Dr. Rescigno added that subtle, rather than overt, inflammation may be all that’s required for closure of the choroid plexus and the subsequent effects on mental health.

In 2015, Dr. Rescigno’s group first described the gut vascular barrier that protects the systemic circulation from gut bacteria or associated bacteria-derived molecules. During intestinal inflammation, such as occurs in IBD, this barrier is compromised and becomes more permeable. This allows microbes to pass across the epithelium of the gut barrier and enter the systemic circulation, including the liver and spleen, explained Dr. Rescigno.

Dr. Rescigno and Dr. Lodato then explored whether this systemic inflammatory condition was connected to the brain along a gut-brain axis and found that it was.

The researchers tested the hypothesis that central nervous system symptoms may be due to vascular changes at the interface between the gut or the brain and elsewhere in the body.

“We set out to test whether opening of the gut vascular barrier would allow gut bacteria to trigger the release of inflammatory molecules that spread to more distant areas, possibly leading to a deficiency of certain nutrients and precipitating mental disorders,” they said.

An experimental preclinical model of the choroid plexus vascular barrier closure led to anxiety-like behavior, as well as short-term memory loss. That this behavior occurred independently of inflammation suggested that it was likely a response to closure itself, they note.

In the noninflammatory state, the epithelium of the choroid plexus filters molecules. Those that are ≤70 kDa are allowed to pass through to the brain. However, the investigators found that during systemic inflammation, this filtration stops, and the blood capillaries of the choroid plexus prevent entry of inflammatory molecules such as cytokines.

Dr. Lodato speculated that when the vascular barrier of the choroid plexus shuts off during the systemic inflammatory state, it responds by bathing the brain in cerebrospinal fluid.

“When the choroid plexus closes, like a door slamming shut, then communication between the brain and the rest of the body is halted. This means that the brain is deprived of certain nutrients and other beneficial molecules that usually enter via the cerebrospinal fluid or enriched of potentially dangerous ones, as drainage could also be affected,” she said.

If confirmed in further studies, these results may open the way to new interventions.
 

‘A significant leap forward’

Commenting on the findings, David T. Rubin, MD, professor of medicine at the University of Chicago, noted that the study’s results represent “a significant leap forward” and that it highlights “another important cost to uncontrolled gut inflammation that is the potential for worsened mental health disorders.”

Dr. Rubin, whose research involves measuring metabolites of the dietary amino acid tryptophan, including melatonin and serotonin, in patients with IBD, added that the findings offer a possible explanation for the association of both Crohn’s disease and ulcerative colitis with anxiety and depressive disorders.

“There was a belief that the association was in the opposite direction, that the mental health disorder was causing or worsening the gut inflammation, but this has been disavowed,” Dr. Rubin said.

“Most recently, the recognition that the major sources of serotonin and other metabolites of tryptophan that come from the gut microbiome has led to the hypothesis that the inflamed bowel and dysbiotic gut biome may in fact be driving the mental health disorders due to the effect of neurotransmitter imbalance,” he added. Dr. Rubin also suggested that the shutdown of the choroid plexus vascular barrier may contribute to this imbalance but that this needs additional study.

“This further supports my ongoing contention that the gut really is the center of the universe,” said Dr. Rubin.

Also commenting on the findings, Miguel Rigueiro, MD, professor in the department of medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, said, “There’s an implication that anxiety and depression and other behavioral health disorders may be explained by this mechanism. If that is the case, there may be a way to target medications against the choroid plexus and potentially treat depression or anxiety.”

This prospect was echoed by Dr. Rubin, who said, “The clinical implication is that treatment of gut inflammation may restore a balance to the neurotransmitters and resolve anxiety or depressive disorders.”

To identify new therapeutic targets, investigators will study the regions and circuits of the brain that are more susceptible to this closure of the choroid plexus, said Dr. Lodato.

“If these regions are associated with depression or other psychosocial disorders, then this new understanding around the choroid plexus vascular barrier might eventually have implications for helping treat such disorders,” she noted.

Reflecting a general shift from a brain-centric view of some psychosocial disorders to an intestinal-centric one, Dr. Lodato added, “The brain cannot be considered in isolation. It is part of a much larger body, and we need to think this way.”

Dr. Rescigno, Dr. Lodato, and Dr. Rubin report no relevant financial relationships. Dr. Rigueiro has served on advisory boards and as consultant for AbbVie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, SpA, and Bristol-Meyer Squibb.

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

Over half of people who believed they were transgender, transitioned to the opposite sex, but then regretted it and transitioned back – known as detransitioners – felt they did not receive adequate evaluation from a doctor or mental health professional before starting transition, new research indicates.

In what is thought to be the first study to ask whether detransitioners informed their original clinicians of their regret at transitioning, only 24 of the 100 surveyed said they had done so.

This strongly suggests that records on detransition may understate the real numbers, said Lisa Littman, MD, MPH, president of The Institute for Comprehensive Gender Dysphoria Research (ICGDR), who is the sole author of the study, published in Archives of Sexual Behavior.

She stressed that the findings illustrate the complexity surrounding gender dysphoria. “We need to recognize that there are many different types of experiences around gender dysphoria, transition, and detransition,” she told this news organization.

She said there is some resistance among certain health care professionals, and in society in general, to the idea that transitioning is not always successful.
 

‘We need to understand why this is happening’

“Detransition exists and we need to understand why this is happening,” Dr. Littman emphasized.

She observed that some supporters of “rapid transition” do not want to accept that transitioning helps some individuals but harms others.

“In the end, our goals should be providing the right treatment for the right patient, and without a thorough evaluation, clinicians are at serious risk of giving patients the wrong treatment,” she urged.

She noted that, despite some individuals feeling better after transition, these people still felt inclined to detransition because of discrimination and pressure.

“Individuals should not be pressured to detransition, nor should they be pressured to transition. Both types of pressure were reported by respondents.” 

The recently recognized shift from mostly natal males to natal females seeking to transition was borne out by her study data, with the proportion of natal girls who detransitioned at 69%.
 

‘Shedding light’ on often ignored population

Asked to comment on the study, Laura Edwards-Leeper, PhD, a clinical psychologist from Beaverton, Ore., who specializes in gender-diverse and transgender children, welcomed Dr. Littman’s study.

It is, said Dr. Edwards-Leeper, a “critical preliminary step toward shedding light on this often-ignored and dismissed population of individuals who deserve support, compassion, and sometimes medical intervention from health care providers.”

She added that multiple online reports attest to detransitioners feeling they had not received adequate evaluation prior to medically transitioning, as well as many who expressed feeling too ashamed or angry to return to their same clinicians to detransition.

“Littman’s study provides quantitative support for both of these reported experiences, further emphasizing the importance of the field taking a closer look at the processes currently in place for those experiencing gender dysphoria,” said Dr. Edwards-Leeper.

And Miroslav L. Djordjevic, MD, PhD, professor of surgery/urology, University of Belgrade (Serbia), who is a specialist in urogenital reconstructive surgery and has performed over 2,000 gender-reassignment surgeries in transgender individuals, has recently seen many cases of regret after such surgeries, with requests for reversal operations.

“Despite the fact that medical detransition is relatively safe and without severe consequences, surgical detransition presents one of the most difficult issues in transgender medicine,” Dr. Djordjevic told this news organization.

Commending Dr. Littman on her study, he drew attention to some of the bioethical questions that arise relating to those who detransition.

“I ask what happened in the period before medical transitioning? Was there proper psychological care during medical transitioning? Who confirmed their desire for detransition – the same professionals who did the transition?” or someone else, he continued. “And who accepted these individuals for gender-affirming surgery and what were the criteria for this decision?”
 

Substantial study of reasons for both transitioning and detransitioning 

In her article, Dr. Littman describes a 100-strong population of individuals (66 Americans, 9 British, 9 Canadian, 4 Australians, and 12 from “other” nations), ranging in age from 18 years to over 60 years with a mean age of 29.2 years, who had experienced gender dysphoria, chosen to undergo medical and/or surgical transition, and then detransitioned by discontinuing medications, having reversal surgery, or both.

Participants completed a 115-question survey providing data including age at first experience of gender dysphoria, when participants first sought transitioning care and from whom, and whether they felt pressured to do so. Friendship group dynamics were also explored.

Various narratives of participants’ transitioning-detransitioning experiences were gathered and grouped, for example, those related to discrimination pressures, experiences of trauma or mental health conditions prior to transition, and reports of internalized homophobia.

Dr. Edwards-Leeper observed that the study offers a more extensive assessment of reasons for detransitioning than any other prior research in the field, which has been sparse.

A survey published in April found that detransitioners report significant unmet medical and psychological needs, and a lack of compassion and help from medical and mental health practitioners.

But another 2021 study concluded most detransitioners only reverted to their birth sex because of societal or family pressure, discrimination, or shift to a nonbinary identity.

“However, [Dr.] Littman’s study found that only a small percentage actually detransitioned for that reason [23%], whereas the majority detransitioned because of a change in how the individual understood being a male or female, resulting in becoming comfortable in their assigned gender [60%],” noted Dr. Edwards-Leeper.
 

Reasons for detransitioning

Asked to expand upon the motives for detransition identified in her study, Dr. Littman told this news organization: “We found remarkable breadth in the reasons given for detransitioning.” 

“I believe that we were able to capture the diversity of experiences around detransition because we reached out to communities that were strongly ‘protransition’ – like the World Professional Association for Transgender Health – and communities where individuals might be more skeptical about transition being universally beneficial, like detransition forums,” she said.

Speaking to the complexity of the experiences, 87% selected more than one reason for detransitioning.

The most common reason (60%) was becoming more comfortable identifying with their birth sex, followed by having concerns about potential medical complications from transitioning (49.0%).

Regarding those who became more comfortable with their natal sex, Dr. Littman noted that the finding adds “further support that gender dysphoria is not always permanent.”

She added that, “because most gender-dysphoric youth who are allowed to go through puberty grow up to be lesbian, gay, or bisexual (LGB) nontransgender adults, intervening too soon with medical treatments risks derailing their development as LGB individuals.”

Internalized homophobia or difficulty accepting themselves as lesbian, gay, or bisexual was reported by 23% of participants as a reason for transition and subsequent detransition. 

“For these people, transitioning could be interpreted as an attempt to escape the reality of being same-sex attracted and detransitioning was part of accepting themselves as homosexual or bisexual,” explained Dr. Littman.

“Exploring their distress and discomfort around sexual orientation issues may have been more helpful to them than medical and surgical transition or at least an important part of exploration,” she added in the article.
 

Societal pressure, friends, and social media also play a role

The latest first-hand reports also support prior work by Dr. Littman when she first identified the concept she termed rapid-onset gender dysphoria (ROGD) to describe a sudden transgender identification, usually in the early teenage years, and with no prior indication of any gender questioning.

ROGD, Dr. Littman believes, is strongly related to psychosocial factors, such as trauma, mental health problems, or social influence contributing to the development of gender dysphoria.

The current study found that 58% of respondents expressed the belief that the cause of their gender dysphoria was something specific, such as trauma, abuse, or a mental health condition, with respondents suggesting that transitioning prevented, or delayed, them from addressing their underlying mental health conditions. 

One participant is quoted as saying: “I was deeply uncomfortable with my secondary sex characteristics, which I now understand was a result of childhood trauma and associating my secondary sex characteristics with those events.”

Reflecting on their previous identification as transgender, more than a third of respondents reported that someone else told them their feelings meant they were transgender, and they believed them.

“This speaks to the effect social influence can have on people’s interpretation of their own feelings and their development of a transgender identity,” Dr. Littman remarked.

“Participants also listed several social media sources that encouraged them to believe that transitioning would help them,” she added.

Several friendship group dynamics suggestive of social influence were reported by a subset of respondents, including the fact that their friendship groups mocked people who were not transgender and their popularity increased when they announced they were going to transition. 
 

Pendulum has swung too far the other way

Natal females, who in recent years have made up most referrals, were younger than natal males when they sought transition and decided to detransition; and they stayed “transitioned” for a shorter period than natal males. They were also more likely to have experienced a trauma less than 1 year before the onset of gender dysphoria and were more likely to have felt pressured to transition. 

“Because the females in the study transitioned more recently than the males, they may have experienced a culture where there is more of a ‘push’ to transition,” Dr. Littman pointed out.

She added that, “20 years ago, gender-dysphoric patients were most likely to be underdiagnosed and undertreated. Now, the pendulum has swung the other way and patients are, in my opinion, more likely to be overdiagnosed and overtreated. I think we need to aim for somewhere between these two extremes and prioritize people getting the right treatment for the right reason for their distress.”

Dr. Djordjevic added that, with colleagues from Belgrade and the Netherlands, he has published accounts of the experiences of seven individuals who showed regret after gender-affirming surgery.

All of them were born male, “and we confirmed the very poor evaluation and transition process they underwent. We conclude that clinicians should be aware that not everyone with gender identity disorders need or want all elements of hormonal or surgical therapy,” he told this news organization.

Dr. Edwards-Leeper said that more long-term longitudinal studies are needed that follow individuals who undergo transition under different models of care.

“My prediction is that those who first engage in supportive, gender exploratory therapy, followed by comprehensive assessment, will have the best outcomes, perhaps even if they ultimately detransition, as these individuals will know that they did not jump into irreversible interventions too quickly and had time to make the best decision for themselves at the time,” she concluded.

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

Over half of people who believed they were transgender, transitioned to the opposite sex, but then regretted it and transitioned back – known as detransitioners – felt they did not receive adequate evaluation from a doctor or mental health professional before starting transition, new research indicates.

In what is thought to be the first study to ask whether detransitioners informed their original clinicians of their regret at transitioning, only 24 of the 100 surveyed said they had done so.

This strongly suggests that records on detransition may understate the real numbers, said Lisa Littman, MD, MPH, president of The Institute for Comprehensive Gender Dysphoria Research (ICGDR), who is the sole author of the study, published in Archives of Sexual Behavior.

She stressed that the findings illustrate the complexity surrounding gender dysphoria. “We need to recognize that there are many different types of experiences around gender dysphoria, transition, and detransition,” she told this news organization.

She said there is some resistance among certain health care professionals, and in society in general, to the idea that transitioning is not always successful.
 

‘We need to understand why this is happening’

“Detransition exists and we need to understand why this is happening,” Dr. Littman emphasized.

She observed that some supporters of “rapid transition” do not want to accept that transitioning helps some individuals but harms others.

“In the end, our goals should be providing the right treatment for the right patient, and without a thorough evaluation, clinicians are at serious risk of giving patients the wrong treatment,” she urged.

She noted that, despite some individuals feeling better after transition, these people still felt inclined to detransition because of discrimination and pressure.

“Individuals should not be pressured to detransition, nor should they be pressured to transition. Both types of pressure were reported by respondents.” 

The recently recognized shift from mostly natal males to natal females seeking to transition was borne out by her study data, with the proportion of natal girls who detransitioned at 69%.
 

‘Shedding light’ on often ignored population

Asked to comment on the study, Laura Edwards-Leeper, PhD, a clinical psychologist from Beaverton, Ore., who specializes in gender-diverse and transgender children, welcomed Dr. Littman’s study.

It is, said Dr. Edwards-Leeper, a “critical preliminary step toward shedding light on this often-ignored and dismissed population of individuals who deserve support, compassion, and sometimes medical intervention from health care providers.”

She added that multiple online reports attest to detransitioners feeling they had not received adequate evaluation prior to medically transitioning, as well as many who expressed feeling too ashamed or angry to return to their same clinicians to detransition.

“Littman’s study provides quantitative support for both of these reported experiences, further emphasizing the importance of the field taking a closer look at the processes currently in place for those experiencing gender dysphoria,” said Dr. Edwards-Leeper.

And Miroslav L. Djordjevic, MD, PhD, professor of surgery/urology, University of Belgrade (Serbia), who is a specialist in urogenital reconstructive surgery and has performed over 2,000 gender-reassignment surgeries in transgender individuals, has recently seen many cases of regret after such surgeries, with requests for reversal operations.

“Despite the fact that medical detransition is relatively safe and without severe consequences, surgical detransition presents one of the most difficult issues in transgender medicine,” Dr. Djordjevic told this news organization.

Commending Dr. Littman on her study, he drew attention to some of the bioethical questions that arise relating to those who detransition.

“I ask what happened in the period before medical transitioning? Was there proper psychological care during medical transitioning? Who confirmed their desire for detransition – the same professionals who did the transition?” or someone else, he continued. “And who accepted these individuals for gender-affirming surgery and what were the criteria for this decision?”
 

Substantial study of reasons for both transitioning and detransitioning 

In her article, Dr. Littman describes a 100-strong population of individuals (66 Americans, 9 British, 9 Canadian, 4 Australians, and 12 from “other” nations), ranging in age from 18 years to over 60 years with a mean age of 29.2 years, who had experienced gender dysphoria, chosen to undergo medical and/or surgical transition, and then detransitioned by discontinuing medications, having reversal surgery, or both.

Participants completed a 115-question survey providing data including age at first experience of gender dysphoria, when participants first sought transitioning care and from whom, and whether they felt pressured to do so. Friendship group dynamics were also explored.

Various narratives of participants’ transitioning-detransitioning experiences were gathered and grouped, for example, those related to discrimination pressures, experiences of trauma or mental health conditions prior to transition, and reports of internalized homophobia.

Dr. Edwards-Leeper observed that the study offers a more extensive assessment of reasons for detransitioning than any other prior research in the field, which has been sparse.

A survey published in April found that detransitioners report significant unmet medical and psychological needs, and a lack of compassion and help from medical and mental health practitioners.

But another 2021 study concluded most detransitioners only reverted to their birth sex because of societal or family pressure, discrimination, or shift to a nonbinary identity.

“However, [Dr.] Littman’s study found that only a small percentage actually detransitioned for that reason [23%], whereas the majority detransitioned because of a change in how the individual understood being a male or female, resulting in becoming comfortable in their assigned gender [60%],” noted Dr. Edwards-Leeper.
 

Reasons for detransitioning

Asked to expand upon the motives for detransition identified in her study, Dr. Littman told this news organization: “We found remarkable breadth in the reasons given for detransitioning.” 

“I believe that we were able to capture the diversity of experiences around detransition because we reached out to communities that were strongly ‘protransition’ – like the World Professional Association for Transgender Health – and communities where individuals might be more skeptical about transition being universally beneficial, like detransition forums,” she said.

Speaking to the complexity of the experiences, 87% selected more than one reason for detransitioning.

The most common reason (60%) was becoming more comfortable identifying with their birth sex, followed by having concerns about potential medical complications from transitioning (49.0%).

Regarding those who became more comfortable with their natal sex, Dr. Littman noted that the finding adds “further support that gender dysphoria is not always permanent.”

She added that, “because most gender-dysphoric youth who are allowed to go through puberty grow up to be lesbian, gay, or bisexual (LGB) nontransgender adults, intervening too soon with medical treatments risks derailing their development as LGB individuals.”

Internalized homophobia or difficulty accepting themselves as lesbian, gay, or bisexual was reported by 23% of participants as a reason for transition and subsequent detransition. 

“For these people, transitioning could be interpreted as an attempt to escape the reality of being same-sex attracted and detransitioning was part of accepting themselves as homosexual or bisexual,” explained Dr. Littman.

“Exploring their distress and discomfort around sexual orientation issues may have been more helpful to them than medical and surgical transition or at least an important part of exploration,” she added in the article.
 

Societal pressure, friends, and social media also play a role

The latest first-hand reports also support prior work by Dr. Littman when she first identified the concept she termed rapid-onset gender dysphoria (ROGD) to describe a sudden transgender identification, usually in the early teenage years, and with no prior indication of any gender questioning.

ROGD, Dr. Littman believes, is strongly related to psychosocial factors, such as trauma, mental health problems, or social influence contributing to the development of gender dysphoria.

The current study found that 58% of respondents expressed the belief that the cause of their gender dysphoria was something specific, such as trauma, abuse, or a mental health condition, with respondents suggesting that transitioning prevented, or delayed, them from addressing their underlying mental health conditions. 

One participant is quoted as saying: “I was deeply uncomfortable with my secondary sex characteristics, which I now understand was a result of childhood trauma and associating my secondary sex characteristics with those events.”

Reflecting on their previous identification as transgender, more than a third of respondents reported that someone else told them their feelings meant they were transgender, and they believed them.

“This speaks to the effect social influence can have on people’s interpretation of their own feelings and their development of a transgender identity,” Dr. Littman remarked.

“Participants also listed several social media sources that encouraged them to believe that transitioning would help them,” she added.

Several friendship group dynamics suggestive of social influence were reported by a subset of respondents, including the fact that their friendship groups mocked people who were not transgender and their popularity increased when they announced they were going to transition. 
 

Pendulum has swung too far the other way

Natal females, who in recent years have made up most referrals, were younger than natal males when they sought transition and decided to detransition; and they stayed “transitioned” for a shorter period than natal males. They were also more likely to have experienced a trauma less than 1 year before the onset of gender dysphoria and were more likely to have felt pressured to transition. 

“Because the females in the study transitioned more recently than the males, they may have experienced a culture where there is more of a ‘push’ to transition,” Dr. Littman pointed out.

She added that, “20 years ago, gender-dysphoric patients were most likely to be underdiagnosed and undertreated. Now, the pendulum has swung the other way and patients are, in my opinion, more likely to be overdiagnosed and overtreated. I think we need to aim for somewhere between these two extremes and prioritize people getting the right treatment for the right reason for their distress.”

Dr. Djordjevic added that, with colleagues from Belgrade and the Netherlands, he has published accounts of the experiences of seven individuals who showed regret after gender-affirming surgery.

All of them were born male, “and we confirmed the very poor evaluation and transition process they underwent. We conclude that clinicians should be aware that not everyone with gender identity disorders need or want all elements of hormonal or surgical therapy,” he told this news organization.

Dr. Edwards-Leeper said that more long-term longitudinal studies are needed that follow individuals who undergo transition under different models of care.

“My prediction is that those who first engage in supportive, gender exploratory therapy, followed by comprehensive assessment, will have the best outcomes, perhaps even if they ultimately detransition, as these individuals will know that they did not jump into irreversible interventions too quickly and had time to make the best decision for themselves at the time,” she concluded.

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

Over half of people who believed they were transgender, transitioned to the opposite sex, but then regretted it and transitioned back – known as detransitioners – felt they did not receive adequate evaluation from a doctor or mental health professional before starting transition, new research indicates.

In what is thought to be the first study to ask whether detransitioners informed their original clinicians of their regret at transitioning, only 24 of the 100 surveyed said they had done so.

This strongly suggests that records on detransition may understate the real numbers, said Lisa Littman, MD, MPH, president of The Institute for Comprehensive Gender Dysphoria Research (ICGDR), who is the sole author of the study, published in Archives of Sexual Behavior.

She stressed that the findings illustrate the complexity surrounding gender dysphoria. “We need to recognize that there are many different types of experiences around gender dysphoria, transition, and detransition,” she told this news organization.

She said there is some resistance among certain health care professionals, and in society in general, to the idea that transitioning is not always successful.
 

‘We need to understand why this is happening’

“Detransition exists and we need to understand why this is happening,” Dr. Littman emphasized.

She observed that some supporters of “rapid transition” do not want to accept that transitioning helps some individuals but harms others.

“In the end, our goals should be providing the right treatment for the right patient, and without a thorough evaluation, clinicians are at serious risk of giving patients the wrong treatment,” she urged.

She noted that, despite some individuals feeling better after transition, these people still felt inclined to detransition because of discrimination and pressure.

“Individuals should not be pressured to detransition, nor should they be pressured to transition. Both types of pressure were reported by respondents.” 

The recently recognized shift from mostly natal males to natal females seeking to transition was borne out by her study data, with the proportion of natal girls who detransitioned at 69%.
 

‘Shedding light’ on often ignored population

Asked to comment on the study, Laura Edwards-Leeper, PhD, a clinical psychologist from Beaverton, Ore., who specializes in gender-diverse and transgender children, welcomed Dr. Littman’s study.

It is, said Dr. Edwards-Leeper, a “critical preliminary step toward shedding light on this often-ignored and dismissed population of individuals who deserve support, compassion, and sometimes medical intervention from health care providers.”

She added that multiple online reports attest to detransitioners feeling they had not received adequate evaluation prior to medically transitioning, as well as many who expressed feeling too ashamed or angry to return to their same clinicians to detransition.

“Littman’s study provides quantitative support for both of these reported experiences, further emphasizing the importance of the field taking a closer look at the processes currently in place for those experiencing gender dysphoria,” said Dr. Edwards-Leeper.

And Miroslav L. Djordjevic, MD, PhD, professor of surgery/urology, University of Belgrade (Serbia), who is a specialist in urogenital reconstructive surgery and has performed over 2,000 gender-reassignment surgeries in transgender individuals, has recently seen many cases of regret after such surgeries, with requests for reversal operations.

“Despite the fact that medical detransition is relatively safe and without severe consequences, surgical detransition presents one of the most difficult issues in transgender medicine,” Dr. Djordjevic told this news organization.

Commending Dr. Littman on her study, he drew attention to some of the bioethical questions that arise relating to those who detransition.

“I ask what happened in the period before medical transitioning? Was there proper psychological care during medical transitioning? Who confirmed their desire for detransition – the same professionals who did the transition?” or someone else, he continued. “And who accepted these individuals for gender-affirming surgery and what were the criteria for this decision?”
 

Substantial study of reasons for both transitioning and detransitioning 

In her article, Dr. Littman describes a 100-strong population of individuals (66 Americans, 9 British, 9 Canadian, 4 Australians, and 12 from “other” nations), ranging in age from 18 years to over 60 years with a mean age of 29.2 years, who had experienced gender dysphoria, chosen to undergo medical and/or surgical transition, and then detransitioned by discontinuing medications, having reversal surgery, or both.

Participants completed a 115-question survey providing data including age at first experience of gender dysphoria, when participants first sought transitioning care and from whom, and whether they felt pressured to do so. Friendship group dynamics were also explored.

Various narratives of participants’ transitioning-detransitioning experiences were gathered and grouped, for example, those related to discrimination pressures, experiences of trauma or mental health conditions prior to transition, and reports of internalized homophobia.

Dr. Edwards-Leeper observed that the study offers a more extensive assessment of reasons for detransitioning than any other prior research in the field, which has been sparse.

A survey published in April found that detransitioners report significant unmet medical and psychological needs, and a lack of compassion and help from medical and mental health practitioners.

But another 2021 study concluded most detransitioners only reverted to their birth sex because of societal or family pressure, discrimination, or shift to a nonbinary identity.

“However, [Dr.] Littman’s study found that only a small percentage actually detransitioned for that reason [23%], whereas the majority detransitioned because of a change in how the individual understood being a male or female, resulting in becoming comfortable in their assigned gender [60%],” noted Dr. Edwards-Leeper.
 

Reasons for detransitioning

Asked to expand upon the motives for detransition identified in her study, Dr. Littman told this news organization: “We found remarkable breadth in the reasons given for detransitioning.” 

“I believe that we were able to capture the diversity of experiences around detransition because we reached out to communities that were strongly ‘protransition’ – like the World Professional Association for Transgender Health – and communities where individuals might be more skeptical about transition being universally beneficial, like detransition forums,” she said.

Speaking to the complexity of the experiences, 87% selected more than one reason for detransitioning.

The most common reason (60%) was becoming more comfortable identifying with their birth sex, followed by having concerns about potential medical complications from transitioning (49.0%).

Regarding those who became more comfortable with their natal sex, Dr. Littman noted that the finding adds “further support that gender dysphoria is not always permanent.”

She added that, “because most gender-dysphoric youth who are allowed to go through puberty grow up to be lesbian, gay, or bisexual (LGB) nontransgender adults, intervening too soon with medical treatments risks derailing their development as LGB individuals.”

Internalized homophobia or difficulty accepting themselves as lesbian, gay, or bisexual was reported by 23% of participants as a reason for transition and subsequent detransition. 

“For these people, transitioning could be interpreted as an attempt to escape the reality of being same-sex attracted and detransitioning was part of accepting themselves as homosexual or bisexual,” explained Dr. Littman.

“Exploring their distress and discomfort around sexual orientation issues may have been more helpful to them than medical and surgical transition or at least an important part of exploration,” she added in the article.
 

Societal pressure, friends, and social media also play a role

The latest first-hand reports also support prior work by Dr. Littman when she first identified the concept she termed rapid-onset gender dysphoria (ROGD) to describe a sudden transgender identification, usually in the early teenage years, and with no prior indication of any gender questioning.

ROGD, Dr. Littman believes, is strongly related to psychosocial factors, such as trauma, mental health problems, or social influence contributing to the development of gender dysphoria.

The current study found that 58% of respondents expressed the belief that the cause of their gender dysphoria was something specific, such as trauma, abuse, or a mental health condition, with respondents suggesting that transitioning prevented, or delayed, them from addressing their underlying mental health conditions. 

One participant is quoted as saying: “I was deeply uncomfortable with my secondary sex characteristics, which I now understand was a result of childhood trauma and associating my secondary sex characteristics with those events.”

Reflecting on their previous identification as transgender, more than a third of respondents reported that someone else told them their feelings meant they were transgender, and they believed them.

“This speaks to the effect social influence can have on people’s interpretation of their own feelings and their development of a transgender identity,” Dr. Littman remarked.

“Participants also listed several social media sources that encouraged them to believe that transitioning would help them,” she added.

Several friendship group dynamics suggestive of social influence were reported by a subset of respondents, including the fact that their friendship groups mocked people who were not transgender and their popularity increased when they announced they were going to transition. 
 

Pendulum has swung too far the other way

Natal females, who in recent years have made up most referrals, were younger than natal males when they sought transition and decided to detransition; and they stayed “transitioned” for a shorter period than natal males. They were also more likely to have experienced a trauma less than 1 year before the onset of gender dysphoria and were more likely to have felt pressured to transition. 

“Because the females in the study transitioned more recently than the males, they may have experienced a culture where there is more of a ‘push’ to transition,” Dr. Littman pointed out.

She added that, “20 years ago, gender-dysphoric patients were most likely to be underdiagnosed and undertreated. Now, the pendulum has swung the other way and patients are, in my opinion, more likely to be overdiagnosed and overtreated. I think we need to aim for somewhere between these two extremes and prioritize people getting the right treatment for the right reason for their distress.”

Dr. Djordjevic added that, with colleagues from Belgrade and the Netherlands, he has published accounts of the experiences of seven individuals who showed regret after gender-affirming surgery.

All of them were born male, “and we confirmed the very poor evaluation and transition process they underwent. We conclude that clinicians should be aware that not everyone with gender identity disorders need or want all elements of hormonal or surgical therapy,” he told this news organization.

Dr. Edwards-Leeper said that more long-term longitudinal studies are needed that follow individuals who undergo transition under different models of care.

“My prediction is that those who first engage in supportive, gender exploratory therapy, followed by comprehensive assessment, will have the best outcomes, perhaps even if they ultimately detransition, as these individuals will know that they did not jump into irreversible interventions too quickly and had time to make the best decision for themselves at the time,” she concluded.

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

Universal screening for adolescent depression in schools, compared with the usual process of targeting students for referral after observing behaviors, resulted in significantly higher odds of identifying major depressive disorder (MDD) and of starting treatment for it, a study of more than 12,000 students suggests. Findings were published online in JAMA Network Open.

Deepa L. Sekhar, MD, MSc, with the department of pediatrics at Pennsylvania State College of Medicine in Hershey, Pa., and colleagues conducted a randomized clinical trial comparing the two screening methods from November 2018 to November 2020.

The trial included students in grades 9 through 12 enrolled at any of the 14 participating Pennsylvania public high schools. Researchers compared the two groups using mixed-effects logistic regression.

They found that adolescents in the universal screening intervention group had 5.92 times higher odds (95% confidence interval [CI], 5.07-6.93) of being identified with MDD symptoms, 3.30 times higher odds (95% CI, 2.49-4.38) of the Student Assistance Program (SAP) confirming follow-up needs, and 2.07 times higher odds (95% CI, 1.39-3.10) of starting MDD treatment.

The study comprised 12,909 students, with an average age of 16 years. Of those students, 2,687 (20.8%) were Hispanic; 2,891 (22.4%) were non-Hispanic Black, 5,842 (45.3%) were non-Hispanic White; and 1,489 (11.5%) were multiracial or of other race or ethnicity.

In the universal screening intervention (n = 6,473) all students completed the Patient Health Questionnaire–9 (PHQ-9). Students who screened positive proceeded to the Student Assistance Program. Students could receive a targeted referral to SAP if they had concerning behavior beyond the PHQ-9.

In the targeted screening group (n = 6,436), students with behaviors prompting concern for MDD were referred to the Student Assistance Program (SAP), mandated in all Pennsylvania schools. The SAP determined follow-up.

The U.S. Preventive Services Task Force (USPSTF) endorsed primary care screening in 2009 and again in 2016 for all adolescents 12-18 years old.

However, the study authors wrote, most U.S. adolescents (more than 60%) don’t have routine access to preventive health care, which limits primary care offices’ ability to properly address the growing numbers.

“[S]creening is inconsistent, with inequalities by race and ethnicity and region, and potential worsening with the COVID-19 pandemic,” they noted.

Depression rates see sharp increase

Meanwhile, the prevalence of adolescents reporting MDD symptoms has “nearly doubled in the last decade, increasing from 8.3% in 2008 to 14.4% in 2018.”

The American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association recently declared a national emergency in children’s mental health, citing COVID-19’s toll on top of existing challenges.

This study provides further evidence that universal screening is the better approach to identify and treat adolescent depression to save lives, Andres Pumariega, MD, a child and adolescent psychiatrist at University of Florida in Gainesville, told this news organization.

“If you catch these kids early, you can prevent suicide attempts and suicide. You can also prevent complicating costs of care,” he said.

He noted the universal screening removes the potential for bias.

“Relying purely on referral and clinical identification means a lot of kids in minority groups will not be identified and will not be treated accurately. Many clinicians have a problem identifying depression in diverse kids,” he said.

Pushback for universal screening likely

However, he said he has been part of such efforts to implement such programs in Mexico and the United States and said in the Unites States, the political climate will guarantee pushback from having schools more involved in health care and prevention. Recent controversy around COVID-19 vaccines for children illustrates the potential backlash, he said.

Parents often fight such programs as attempts to “label” their children, he said.

“If I have cancer, I sure want to be labeled. A label is used to get them help. We need to find ways to educate parents and support them in facing these issues,” he added.

One concern he has with this intervention is having the SAPs, composed largely of nonclinicians, be the triage point “instead of doing that objectively through objective criteria and by clinicians,” he said. “If we are to have a comprehensive health system where we can serve all kids and manage costs, schools need to be a major part of it.”

School settings offer the chance to see more children, collaborate with teachers and counselors, and integrate results with educational outcomes, he added.

In the study by Sekhar and colleagues, 7 of the 14 schools were classified as urban, with a median size of 370 students.

Researchers noted that the benefit of the universal screening is likely understated because of COVID-19–related school closures during the study period. The closures meant screening wasn’t completed for 7% of students.

The authors concluded that universal screening finds teens living with depression who otherwise would not be found. They said such a program likely works best in schools with strong SAP.

“Adolescents’ consistent contact with schools has been used to support physical health screenings that affect academic success,” the authors wrote. “Major depressive disorder similarly affects academic success, suggesting school-based screening may be especially beneficial.”

In the past 3 years, Dr. Sekhar reported receiving funding from Pfizer through the American Academy of Pediatrics, the Penn State Clinical and Translational Science Awards Program, and a Eugene Washington Patient-Centered Outcomes Research Institute Engagement Award. Full disclosures for coauthors are available in the journal article.

This work was supported in part by the Patient-Centered Outcomes Research Institute. The use of REDCap (Research Electronic Data Capture) in this project was supported by the National Institutes of Health.

Universal screening for adolescent depression in schools, compared with the usual process of targeting students for referral after observing behaviors, resulted in significantly higher odds of identifying major depressive disorder (MDD) and of starting treatment for it, a study of more than 12,000 students suggests. Findings were published online in JAMA Network Open.

Deepa L. Sekhar, MD, MSc, with the department of pediatrics at Pennsylvania State College of Medicine in Hershey, Pa., and colleagues conducted a randomized clinical trial comparing the two screening methods from November 2018 to November 2020.

The trial included students in grades 9 through 12 enrolled at any of the 14 participating Pennsylvania public high schools. Researchers compared the two groups using mixed-effects logistic regression.

They found that adolescents in the universal screening intervention group had 5.92 times higher odds (95% confidence interval [CI], 5.07-6.93) of being identified with MDD symptoms, 3.30 times higher odds (95% CI, 2.49-4.38) of the Student Assistance Program (SAP) confirming follow-up needs, and 2.07 times higher odds (95% CI, 1.39-3.10) of starting MDD treatment.

The study comprised 12,909 students, with an average age of 16 years. Of those students, 2,687 (20.8%) were Hispanic; 2,891 (22.4%) were non-Hispanic Black, 5,842 (45.3%) were non-Hispanic White; and 1,489 (11.5%) were multiracial or of other race or ethnicity.

In the universal screening intervention (n = 6,473) all students completed the Patient Health Questionnaire–9 (PHQ-9). Students who screened positive proceeded to the Student Assistance Program. Students could receive a targeted referral to SAP if they had concerning behavior beyond the PHQ-9.

In the targeted screening group (n = 6,436), students with behaviors prompting concern for MDD were referred to the Student Assistance Program (SAP), mandated in all Pennsylvania schools. The SAP determined follow-up.

The U.S. Preventive Services Task Force (USPSTF) endorsed primary care screening in 2009 and again in 2016 for all adolescents 12-18 years old.

However, the study authors wrote, most U.S. adolescents (more than 60%) don’t have routine access to preventive health care, which limits primary care offices’ ability to properly address the growing numbers.

“[S]creening is inconsistent, with inequalities by race and ethnicity and region, and potential worsening with the COVID-19 pandemic,” they noted.

Depression rates see sharp increase

Meanwhile, the prevalence of adolescents reporting MDD symptoms has “nearly doubled in the last decade, increasing from 8.3% in 2008 to 14.4% in 2018.”

The American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association recently declared a national emergency in children’s mental health, citing COVID-19’s toll on top of existing challenges.

This study provides further evidence that universal screening is the better approach to identify and treat adolescent depression to save lives, Andres Pumariega, MD, a child and adolescent psychiatrist at University of Florida in Gainesville, told this news organization.

“If you catch these kids early, you can prevent suicide attempts and suicide. You can also prevent complicating costs of care,” he said.

He noted the universal screening removes the potential for bias.

“Relying purely on referral and clinical identification means a lot of kids in minority groups will not be identified and will not be treated accurately. Many clinicians have a problem identifying depression in diverse kids,” he said.

Pushback for universal screening likely

However, he said he has been part of such efforts to implement such programs in Mexico and the United States and said in the Unites States, the political climate will guarantee pushback from having schools more involved in health care and prevention. Recent controversy around COVID-19 vaccines for children illustrates the potential backlash, he said.

Parents often fight such programs as attempts to “label” their children, he said.

“If I have cancer, I sure want to be labeled. A label is used to get them help. We need to find ways to educate parents and support them in facing these issues,” he added.

One concern he has with this intervention is having the SAPs, composed largely of nonclinicians, be the triage point “instead of doing that objectively through objective criteria and by clinicians,” he said. “If we are to have a comprehensive health system where we can serve all kids and manage costs, schools need to be a major part of it.”

School settings offer the chance to see more children, collaborate with teachers and counselors, and integrate results with educational outcomes, he added.

In the study by Sekhar and colleagues, 7 of the 14 schools were classified as urban, with a median size of 370 students.

Researchers noted that the benefit of the universal screening is likely understated because of COVID-19–related school closures during the study period. The closures meant screening wasn’t completed for 7% of students.

The authors concluded that universal screening finds teens living with depression who otherwise would not be found. They said such a program likely works best in schools with strong SAP.

“Adolescents’ consistent contact with schools has been used to support physical health screenings that affect academic success,” the authors wrote. “Major depressive disorder similarly affects academic success, suggesting school-based screening may be especially beneficial.”

In the past 3 years, Dr. Sekhar reported receiving funding from Pfizer through the American Academy of Pediatrics, the Penn State Clinical and Translational Science Awards Program, and a Eugene Washington Patient-Centered Outcomes Research Institute Engagement Award. Full disclosures for coauthors are available in the journal article.

This work was supported in part by the Patient-Centered Outcomes Research Institute. The use of REDCap (Research Electronic Data Capture) in this project was supported by the National Institutes of Health.

Universal screening for adolescent depression in schools, compared with the usual process of targeting students for referral after observing behaviors, resulted in significantly higher odds of identifying major depressive disorder (MDD) and of starting treatment for it, a study of more than 12,000 students suggests. Findings were published online in JAMA Network Open.

Deepa L. Sekhar, MD, MSc, with the department of pediatrics at Pennsylvania State College of Medicine in Hershey, Pa., and colleagues conducted a randomized clinical trial comparing the two screening methods from November 2018 to November 2020.

The trial included students in grades 9 through 12 enrolled at any of the 14 participating Pennsylvania public high schools. Researchers compared the two groups using mixed-effects logistic regression.

They found that adolescents in the universal screening intervention group had 5.92 times higher odds (95% confidence interval [CI], 5.07-6.93) of being identified with MDD symptoms, 3.30 times higher odds (95% CI, 2.49-4.38) of the Student Assistance Program (SAP) confirming follow-up needs, and 2.07 times higher odds (95% CI, 1.39-3.10) of starting MDD treatment.

The study comprised 12,909 students, with an average age of 16 years. Of those students, 2,687 (20.8%) were Hispanic; 2,891 (22.4%) were non-Hispanic Black, 5,842 (45.3%) were non-Hispanic White; and 1,489 (11.5%) were multiracial or of other race or ethnicity.

In the universal screening intervention (n = 6,473) all students completed the Patient Health Questionnaire–9 (PHQ-9). Students who screened positive proceeded to the Student Assistance Program. Students could receive a targeted referral to SAP if they had concerning behavior beyond the PHQ-9.

In the targeted screening group (n = 6,436), students with behaviors prompting concern for MDD were referred to the Student Assistance Program (SAP), mandated in all Pennsylvania schools. The SAP determined follow-up.

The U.S. Preventive Services Task Force (USPSTF) endorsed primary care screening in 2009 and again in 2016 for all adolescents 12-18 years old.

However, the study authors wrote, most U.S. adolescents (more than 60%) don’t have routine access to preventive health care, which limits primary care offices’ ability to properly address the growing numbers.

“[S]creening is inconsistent, with inequalities by race and ethnicity and region, and potential worsening with the COVID-19 pandemic,” they noted.

Depression rates see sharp increase

Meanwhile, the prevalence of adolescents reporting MDD symptoms has “nearly doubled in the last decade, increasing from 8.3% in 2008 to 14.4% in 2018.”

The American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association recently declared a national emergency in children’s mental health, citing COVID-19’s toll on top of existing challenges.

This study provides further evidence that universal screening is the better approach to identify and treat adolescent depression to save lives, Andres Pumariega, MD, a child and adolescent psychiatrist at University of Florida in Gainesville, told this news organization.

“If you catch these kids early, you can prevent suicide attempts and suicide. You can also prevent complicating costs of care,” he said.

He noted the universal screening removes the potential for bias.

“Relying purely on referral and clinical identification means a lot of kids in minority groups will not be identified and will not be treated accurately. Many clinicians have a problem identifying depression in diverse kids,” he said.

Pushback for universal screening likely

However, he said he has been part of such efforts to implement such programs in Mexico and the United States and said in the Unites States, the political climate will guarantee pushback from having schools more involved in health care and prevention. Recent controversy around COVID-19 vaccines for children illustrates the potential backlash, he said.

Parents often fight such programs as attempts to “label” their children, he said.

“If I have cancer, I sure want to be labeled. A label is used to get them help. We need to find ways to educate parents and support them in facing these issues,” he added.

One concern he has with this intervention is having the SAPs, composed largely of nonclinicians, be the triage point “instead of doing that objectively through objective criteria and by clinicians,” he said. “If we are to have a comprehensive health system where we can serve all kids and manage costs, schools need to be a major part of it.”

School settings offer the chance to see more children, collaborate with teachers and counselors, and integrate results with educational outcomes, he added.

In the study by Sekhar and colleagues, 7 of the 14 schools were classified as urban, with a median size of 370 students.

Researchers noted that the benefit of the universal screening is likely understated because of COVID-19–related school closures during the study period. The closures meant screening wasn’t completed for 7% of students.

The authors concluded that universal screening finds teens living with depression who otherwise would not be found. They said such a program likely works best in schools with strong SAP.

“Adolescents’ consistent contact with schools has been used to support physical health screenings that affect academic success,” the authors wrote. “Major depressive disorder similarly affects academic success, suggesting school-based screening may be especially beneficial.”

In the past 3 years, Dr. Sekhar reported receiving funding from Pfizer through the American Academy of Pediatrics, the Penn State Clinical and Translational Science Awards Program, and a Eugene Washington Patient-Centered Outcomes Research Institute Engagement Award. Full disclosures for coauthors are available in the journal article.

This work was supported in part by the Patient-Centered Outcomes Research Institute. The use of REDCap (Research Electronic Data Capture) in this project was supported by the National Institutes of Health.

Increased mental health needs, higher acuity from delayed appointments, and added questions and conversations surrounding COVID-19 are forcing primary care offices to rethink priorities in office visits.

Evidence of this came from the latest Primary Care Collaborative (PCC) survey, which found that primary care clinicians are seeing more complex patients requiring longer appointments in the wake of COVID-19.

The PCC with the Larry A. Green Center regularly surveys primary care clinicians. This round of questions came August 14-17 and included 1,263 respondents from 49 states, the District of Columbia, and two territories.

More than 7 in 10 (71%) respondents said their patients are more complex and nearly the same percentage said appointments are taking more time.

Ann Greiner, president and CEO of the PCC, said in an interview that 55% of respondents reported that clinicians are struggling to keep up with pent-up demand after patients have delayed or canceled care. Sixty-five percent in the survey said they had seen a rise in children’s mental health issues, and 58% said they were unsure how to help their patients with long COVID.

In addition, primary care clinicians are having repeated conversations with patients on why they should get a vaccine and which one.

“I think that’s adding to the complexity. There is a lot going on here with patient trust,” Ms. Greiner said.
 

‘We’re going to be playing catch-up’

Jacqueline Fincher, MD, an internist in Thompson, Ga., said in an interview that appointments have gotten longer and more complex in the wake of the pandemic – “no question.”

The immediate past president of the American College of Physicians is seeing patients with chronic disease that has gone untreated for sometimes a year or more, she said.

“Their blood pressure was not under good control, they were under more stress, their sugars were up and weren’t being followed as closely for conditions such as congestive heart failure,” she said.

Dr. Fincher, who works in a rural practice 40 miles from Augusta, Ga., with her physician husband and two other physicians, said patients are ready to come back in, “but I don’t have enough slots for them.”

She said she prioritizes what to help patients with first and schedules the next tier for the next appointment, but added, “honestly, over the next 2 years we’re going to be playing catch-up.”

At the same time, the CDC has estimated that 45% of U.S. adults are at increased risk for complications from COVID-19 because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. Rates ranged from 19.8% for people 18-29 years old to 80.7% for people over 80 years of age.
 

Long COVID could overwhelm existing health care capacity

Primary care physicians are also having to diagnose sometimes “invisible” symptoms after people have recovered from acute COVID-19 infection. Diagnosing takes intent listening to patients who describe symptoms that tests can’t confirm.

As this news organization has previously reported, half of COVID-19 survivors report postacute sequelae of COVID-19 (PASC) lasting longer than 6 months.

“These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries,” the authors wrote.
 

Anxiety, depression ‘have gone off the charts’

Danielle Loeb, MD, MPH, associate professor of internal medicine at the University of Colorado in Denver, who studies complexity in primary care, said in the wake of COVID-19, more patients have developed “new, serious anxiety.”

Courtesy Dr. Danielle Loeb

“That got extremely exacerbated during the pandemic. Anxiety and depression have gone off the charts,” said Dr. Loeb, who prefers the pronoun “they.”

Dr. Loeb cares for a large number of transgender patients. As offices reopen, some patients are having trouble reintegrating into the workplace and resuming social contacts. The primary care doctor says appointments can get longer because of the need to complete tasks, such as filling out forms for Family Medical Leave Act for those not yet ready to return to work.

COVID-19–related fears are keeping many patients from coming into the office, Dr. Loeb said, either from fear of exposure or because they have mental health issues that keep them from feeling safe leaving the house.

“That really affects my ability to care for them,” they said.

Loss of employment in the pandemic or fear of job loss and subsequent changing of insurance has complicated primary care in terms of treatment and administrative tasks, according to Dr. Loeb.

To help treat patients with acute mental health issues and manage other patients, Dr. Loeb’s practice has brought in a social worker and a therapist.

Team-based care is key in the survival of primary care practices, though providing that is difficult in the smaller clinics because of the critical mass of patients needed to make it viable, they said.

“It’s the only answer. It’s the only way you don’t drown,” Dr. Loeb added. “I’m not drowning, and I credit that to my clinic having the help to support the mental health piece of things.”
 

Rethinking workflow

Tricia McGinnis, MPP, MPH, executive vice president of the nonprofit Center for Health Care Strategies (CHCS) says complexity has forced rethinking workflow.

“A lot of the trends we’re seeing in primary care were there pre-COVID, but COVID has exacerbated those trends,” she said in an interview.

“The good news ... is that it was already becoming clear that primary care needed to provide basic mental health services and integrate with behavioral health. It had also become clear that effective primary care needed to address social issues that keep patients from accessing health care,” she said.

Expanding care teams, as Dr. Loeb mentioned, is a key strategy, according to Ms. McGinnis. Potential teams would include the clinical staff, but also social workers and community health workers – people who come from the community primary care is serving who can help build trust with patients and connect the patient to the primary care team.

“There’s a lot that needs to happen that the clinician doesn’t need to do,” she said.

Telehealth can be a big factor in coordinating the team, Ms. McGinnis added.

“It’s thinking less about who’s doing the work, but more about the work that needs to be done to keep people healthy. Then let’s think about the type of workers best suited to perform those tasks,” she said.

As for reimbursing more complex care, population-based, up-front capitated payments linked to high-quality care and better outcomes will need to replace fee-for-service models, according to Ms. McGinnis.

That will provide reliable incomes for primary care offices, but also flexibility in how each patient with different levels of complexity is managed, she said.

Ms. Greiner, Dr. Fincher, Dr. Loeb, and Ms. McGinnis have no relevant financial relationships.

Increased mental health needs, higher acuity from delayed appointments, and added questions and conversations surrounding COVID-19 are forcing primary care offices to rethink priorities in office visits.

Evidence of this came from the latest Primary Care Collaborative (PCC) survey, which found that primary care clinicians are seeing more complex patients requiring longer appointments in the wake of COVID-19.

The PCC with the Larry A. Green Center regularly surveys primary care clinicians. This round of questions came August 14-17 and included 1,263 respondents from 49 states, the District of Columbia, and two territories.

More than 7 in 10 (71%) respondents said their patients are more complex and nearly the same percentage said appointments are taking more time.

Ann Greiner, president and CEO of the PCC, said in an interview that 55% of respondents reported that clinicians are struggling to keep up with pent-up demand after patients have delayed or canceled care. Sixty-five percent in the survey said they had seen a rise in children’s mental health issues, and 58% said they were unsure how to help their patients with long COVID.

In addition, primary care clinicians are having repeated conversations with patients on why they should get a vaccine and which one.

“I think that’s adding to the complexity. There is a lot going on here with patient trust,” Ms. Greiner said.
 

‘We’re going to be playing catch-up’

Jacqueline Fincher, MD, an internist in Thompson, Ga., said in an interview that appointments have gotten longer and more complex in the wake of the pandemic – “no question.”

The immediate past president of the American College of Physicians is seeing patients with chronic disease that has gone untreated for sometimes a year or more, she said.

“Their blood pressure was not under good control, they were under more stress, their sugars were up and weren’t being followed as closely for conditions such as congestive heart failure,” she said.

Dr. Fincher, who works in a rural practice 40 miles from Augusta, Ga., with her physician husband and two other physicians, said patients are ready to come back in, “but I don’t have enough slots for them.”

She said she prioritizes what to help patients with first and schedules the next tier for the next appointment, but added, “honestly, over the next 2 years we’re going to be playing catch-up.”

At the same time, the CDC has estimated that 45% of U.S. adults are at increased risk for complications from COVID-19 because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. Rates ranged from 19.8% for people 18-29 years old to 80.7% for people over 80 years of age.
 

Long COVID could overwhelm existing health care capacity

Primary care physicians are also having to diagnose sometimes “invisible” symptoms after people have recovered from acute COVID-19 infection. Diagnosing takes intent listening to patients who describe symptoms that tests can’t confirm.

As this news organization has previously reported, half of COVID-19 survivors report postacute sequelae of COVID-19 (PASC) lasting longer than 6 months.

“These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries,” the authors wrote.
 

Anxiety, depression ‘have gone off the charts’

Danielle Loeb, MD, MPH, associate professor of internal medicine at the University of Colorado in Denver, who studies complexity in primary care, said in the wake of COVID-19, more patients have developed “new, serious anxiety.”

Courtesy Dr. Danielle Loeb

“That got extremely exacerbated during the pandemic. Anxiety and depression have gone off the charts,” said Dr. Loeb, who prefers the pronoun “they.”

Dr. Loeb cares for a large number of transgender patients. As offices reopen, some patients are having trouble reintegrating into the workplace and resuming social contacts. The primary care doctor says appointments can get longer because of the need to complete tasks, such as filling out forms for Family Medical Leave Act for those not yet ready to return to work.

COVID-19–related fears are keeping many patients from coming into the office, Dr. Loeb said, either from fear of exposure or because they have mental health issues that keep them from feeling safe leaving the house.

“That really affects my ability to care for them,” they said.

Loss of employment in the pandemic or fear of job loss and subsequent changing of insurance has complicated primary care in terms of treatment and administrative tasks, according to Dr. Loeb.

To help treat patients with acute mental health issues and manage other patients, Dr. Loeb’s practice has brought in a social worker and a therapist.

Team-based care is key in the survival of primary care practices, though providing that is difficult in the smaller clinics because of the critical mass of patients needed to make it viable, they said.

“It’s the only answer. It’s the only way you don’t drown,” Dr. Loeb added. “I’m not drowning, and I credit that to my clinic having the help to support the mental health piece of things.”
 

Rethinking workflow

Tricia McGinnis, MPP, MPH, executive vice president of the nonprofit Center for Health Care Strategies (CHCS) says complexity has forced rethinking workflow.

“A lot of the trends we’re seeing in primary care were there pre-COVID, but COVID has exacerbated those trends,” she said in an interview.

“The good news ... is that it was already becoming clear that primary care needed to provide basic mental health services and integrate with behavioral health. It had also become clear that effective primary care needed to address social issues that keep patients from accessing health care,” she said.

Expanding care teams, as Dr. Loeb mentioned, is a key strategy, according to Ms. McGinnis. Potential teams would include the clinical staff, but also social workers and community health workers – people who come from the community primary care is serving who can help build trust with patients and connect the patient to the primary care team.

“There’s a lot that needs to happen that the clinician doesn’t need to do,” she said.

Telehealth can be a big factor in coordinating the team, Ms. McGinnis added.

“It’s thinking less about who’s doing the work, but more about the work that needs to be done to keep people healthy. Then let’s think about the type of workers best suited to perform those tasks,” she said.

As for reimbursing more complex care, population-based, up-front capitated payments linked to high-quality care and better outcomes will need to replace fee-for-service models, according to Ms. McGinnis.

That will provide reliable incomes for primary care offices, but also flexibility in how each patient with different levels of complexity is managed, she said.

Ms. Greiner, Dr. Fincher, Dr. Loeb, and Ms. McGinnis have no relevant financial relationships.

Increased mental health needs, higher acuity from delayed appointments, and added questions and conversations surrounding COVID-19 are forcing primary care offices to rethink priorities in office visits.

Evidence of this came from the latest Primary Care Collaborative (PCC) survey, which found that primary care clinicians are seeing more complex patients requiring longer appointments in the wake of COVID-19.

The PCC with the Larry A. Green Center regularly surveys primary care clinicians. This round of questions came August 14-17 and included 1,263 respondents from 49 states, the District of Columbia, and two territories.

More than 7 in 10 (71%) respondents said their patients are more complex and nearly the same percentage said appointments are taking more time.

Ann Greiner, president and CEO of the PCC, said in an interview that 55% of respondents reported that clinicians are struggling to keep up with pent-up demand after patients have delayed or canceled care. Sixty-five percent in the survey said they had seen a rise in children’s mental health issues, and 58% said they were unsure how to help their patients with long COVID.

In addition, primary care clinicians are having repeated conversations with patients on why they should get a vaccine and which one.

“I think that’s adding to the complexity. There is a lot going on here with patient trust,” Ms. Greiner said.
 

‘We’re going to be playing catch-up’

Jacqueline Fincher, MD, an internist in Thompson, Ga., said in an interview that appointments have gotten longer and more complex in the wake of the pandemic – “no question.”

The immediate past president of the American College of Physicians is seeing patients with chronic disease that has gone untreated for sometimes a year or more, she said.

“Their blood pressure was not under good control, they were under more stress, their sugars were up and weren’t being followed as closely for conditions such as congestive heart failure,” she said.

Dr. Fincher, who works in a rural practice 40 miles from Augusta, Ga., with her physician husband and two other physicians, said patients are ready to come back in, “but I don’t have enough slots for them.”

She said she prioritizes what to help patients with first and schedules the next tier for the next appointment, but added, “honestly, over the next 2 years we’re going to be playing catch-up.”

At the same time, the CDC has estimated that 45% of U.S. adults are at increased risk for complications from COVID-19 because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. Rates ranged from 19.8% for people 18-29 years old to 80.7% for people over 80 years of age.
 

Long COVID could overwhelm existing health care capacity

Primary care physicians are also having to diagnose sometimes “invisible” symptoms after people have recovered from acute COVID-19 infection. Diagnosing takes intent listening to patients who describe symptoms that tests can’t confirm.

As this news organization has previously reported, half of COVID-19 survivors report postacute sequelae of COVID-19 (PASC) lasting longer than 6 months.

“These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries,” the authors wrote.
 

Anxiety, depression ‘have gone off the charts’

Danielle Loeb, MD, MPH, associate professor of internal medicine at the University of Colorado in Denver, who studies complexity in primary care, said in the wake of COVID-19, more patients have developed “new, serious anxiety.”

Courtesy Dr. Danielle Loeb

“That got extremely exacerbated during the pandemic. Anxiety and depression have gone off the charts,” said Dr. Loeb, who prefers the pronoun “they.”

Dr. Loeb cares for a large number of transgender patients. As offices reopen, some patients are having trouble reintegrating into the workplace and resuming social contacts. The primary care doctor says appointments can get longer because of the need to complete tasks, such as filling out forms for Family Medical Leave Act for those not yet ready to return to work.

COVID-19–related fears are keeping many patients from coming into the office, Dr. Loeb said, either from fear of exposure or because they have mental health issues that keep them from feeling safe leaving the house.

“That really affects my ability to care for them,” they said.

Loss of employment in the pandemic or fear of job loss and subsequent changing of insurance has complicated primary care in terms of treatment and administrative tasks, according to Dr. Loeb.

To help treat patients with acute mental health issues and manage other patients, Dr. Loeb’s practice has brought in a social worker and a therapist.

Team-based care is key in the survival of primary care practices, though providing that is difficult in the smaller clinics because of the critical mass of patients needed to make it viable, they said.

“It’s the only answer. It’s the only way you don’t drown,” Dr. Loeb added. “I’m not drowning, and I credit that to my clinic having the help to support the mental health piece of things.”
 

Rethinking workflow

Tricia McGinnis, MPP, MPH, executive vice president of the nonprofit Center for Health Care Strategies (CHCS) says complexity has forced rethinking workflow.

“A lot of the trends we’re seeing in primary care were there pre-COVID, but COVID has exacerbated those trends,” she said in an interview.

“The good news ... is that it was already becoming clear that primary care needed to provide basic mental health services and integrate with behavioral health. It had also become clear that effective primary care needed to address social issues that keep patients from accessing health care,” she said.

Expanding care teams, as Dr. Loeb mentioned, is a key strategy, according to Ms. McGinnis. Potential teams would include the clinical staff, but also social workers and community health workers – people who come from the community primary care is serving who can help build trust with patients and connect the patient to the primary care team.

“There’s a lot that needs to happen that the clinician doesn’t need to do,” she said.

Telehealth can be a big factor in coordinating the team, Ms. McGinnis added.

“It’s thinking less about who’s doing the work, but more about the work that needs to be done to keep people healthy. Then let’s think about the type of workers best suited to perform those tasks,” she said.

As for reimbursing more complex care, population-based, up-front capitated payments linked to high-quality care and better outcomes will need to replace fee-for-service models, according to Ms. McGinnis.

That will provide reliable incomes for primary care offices, but also flexibility in how each patient with different levels of complexity is managed, she said.

Ms. Greiner, Dr. Fincher, Dr. Loeb, and Ms. McGinnis have no relevant financial relationships.