Mental Health

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

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

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

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

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

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

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Obsessive-compulsive disorder (OCD) is linked to a twofold increased risk for all-cause mortality and a heightened risk for death from both natural and unnatural causes, a new study showed.

METHODOLOGY:

• Investigators studied a population-based cohort (58% female) of 61,378 people with OCD and 613,780 unaffected individuals from several Swedish population registers and a sibling cohort of 34,085 people with OCD (58% female) and 47,874 unaffected full siblings (48% female).
• The median 8.1-year follow-up and median age at first diagnosis of OCD were 27 years.
• The researchers used Cox proportional hazard models, adjusting for birth year, sex, county, country of birth (Sweden vs abroad), and sociodemographic variables.

TAKEAWAY:

• Compared with controls, individuals with OCD had almost twice the risk for all-cause mortality (adjusted hazard ratio [aHR], 1.82; 95% CI, 1.76-1.89), an almost threefold higher risk for mortality due to unnatural causes (aHR, 3.30; 95% CI, 3.05-3.57), and a higher risk for mortality due to natural causes (aHR, 1.31; 95% CI, 1.24-1.37).
• Of all the unnatural causes of death, suicide was most common (hazard ratio [HR], 4.90; 95% CI, 4.40-5.46), followed by accidents (HR, 1.92; 95% CI, 1.68-2.19).
• Similar results were found in the sibling comparison, where the HR of all-cause mortality was 1.85 (95% CI, 1.67-2.03), death from natural causes was 1.51 (95% CI, 1.35-1.68), and death from unnatural causes was 3.10 (95% CI, 2.52-3.80).
• Natural causes of death that were higher in the OCD vs non-OCD cohort included endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems.

IN PRACTICE:

“Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD,” the authors wrote.

SOURCE:

Lorena Fernández de la Cruz, PhD, of Karolinska Institutet, Solna, Sweden, led the study, which was published online on January 17 in the British Medical Journal.

LIMITATIONS:

The study does not establish causality. Registry data used by the investigators only included diagnoses made in specialist care and may not have included diagnoses made in other settings. It is also unclear whether the findings, derived from a Swedish population, can be generalized to other populations, health systems, and medical practices.

DISCLOSURES:

The study was funded by the Swedish Council for Health, Working Life and Welfare, Region Stockholm, the Swedish Society of Medicine, and Karolinska Institutet. Dr. de la Cruz received royalties for contributing articles to UpToDate and Wolters Kluwer Health and for editorial work from Elsevier outside the submitted work. See the paper for disclosures of the other authors.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Obsessive-compulsive disorder (OCD) is linked to a twofold increased risk for all-cause mortality and a heightened risk for death from both natural and unnatural causes, a new study showed.

METHODOLOGY:

• Investigators studied a population-based cohort (58% female) of 61,378 people with OCD and 613,780 unaffected individuals from several Swedish population registers and a sibling cohort of 34,085 people with OCD (58% female) and 47,874 unaffected full siblings (48% female).
• The median 8.1-year follow-up and median age at first diagnosis of OCD were 27 years.
• The researchers used Cox proportional hazard models, adjusting for birth year, sex, county, country of birth (Sweden vs abroad), and sociodemographic variables.

TAKEAWAY:

• Compared with controls, individuals with OCD had almost twice the risk for all-cause mortality (adjusted hazard ratio [aHR], 1.82; 95% CI, 1.76-1.89), an almost threefold higher risk for mortality due to unnatural causes (aHR, 3.30; 95% CI, 3.05-3.57), and a higher risk for mortality due to natural causes (aHR, 1.31; 95% CI, 1.24-1.37).
• Of all the unnatural causes of death, suicide was most common (hazard ratio [HR], 4.90; 95% CI, 4.40-5.46), followed by accidents (HR, 1.92; 95% CI, 1.68-2.19).
• Similar results were found in the sibling comparison, where the HR of all-cause mortality was 1.85 (95% CI, 1.67-2.03), death from natural causes was 1.51 (95% CI, 1.35-1.68), and death from unnatural causes was 3.10 (95% CI, 2.52-3.80).
• Natural causes of death that were higher in the OCD vs non-OCD cohort included endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems.

IN PRACTICE:

“Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD,” the authors wrote.

SOURCE:

Lorena Fernández de la Cruz, PhD, of Karolinska Institutet, Solna, Sweden, led the study, which was published online on January 17 in the British Medical Journal.

LIMITATIONS:

The study does not establish causality. Registry data used by the investigators only included diagnoses made in specialist care and may not have included diagnoses made in other settings. It is also unclear whether the findings, derived from a Swedish population, can be generalized to other populations, health systems, and medical practices.

DISCLOSURES:

The study was funded by the Swedish Council for Health, Working Life and Welfare, Region Stockholm, the Swedish Society of Medicine, and Karolinska Institutet. Dr. de la Cruz received royalties for contributing articles to UpToDate and Wolters Kluwer Health and for editorial work from Elsevier outside the submitted work. See the paper for disclosures of the other authors.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Obsessive-compulsive disorder (OCD) is linked to a twofold increased risk for all-cause mortality and a heightened risk for death from both natural and unnatural causes, a new study showed.

METHODOLOGY:

• Investigators studied a population-based cohort (58% female) of 61,378 people with OCD and 613,780 unaffected individuals from several Swedish population registers and a sibling cohort of 34,085 people with OCD (58% female) and 47,874 unaffected full siblings (48% female).
• The median 8.1-year follow-up and median age at first diagnosis of OCD were 27 years.
• The researchers used Cox proportional hazard models, adjusting for birth year, sex, county, country of birth (Sweden vs abroad), and sociodemographic variables.

TAKEAWAY:

• Compared with controls, individuals with OCD had almost twice the risk for all-cause mortality (adjusted hazard ratio [aHR], 1.82; 95% CI, 1.76-1.89), an almost threefold higher risk for mortality due to unnatural causes (aHR, 3.30; 95% CI, 3.05-3.57), and a higher risk for mortality due to natural causes (aHR, 1.31; 95% CI, 1.24-1.37).
• Of all the unnatural causes of death, suicide was most common (hazard ratio [HR], 4.90; 95% CI, 4.40-5.46), followed by accidents (HR, 1.92; 95% CI, 1.68-2.19).
• Similar results were found in the sibling comparison, where the HR of all-cause mortality was 1.85 (95% CI, 1.67-2.03), death from natural causes was 1.51 (95% CI, 1.35-1.68), and death from unnatural causes was 3.10 (95% CI, 2.52-3.80).
• Natural causes of death that were higher in the OCD vs non-OCD cohort included endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems.

IN PRACTICE:

“Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD,” the authors wrote.

SOURCE:

Lorena Fernández de la Cruz, PhD, of Karolinska Institutet, Solna, Sweden, led the study, which was published online on January 17 in the British Medical Journal.

LIMITATIONS:

The study does not establish causality. Registry data used by the investigators only included diagnoses made in specialist care and may not have included diagnoses made in other settings. It is also unclear whether the findings, derived from a Swedish population, can be generalized to other populations, health systems, and medical practices.

DISCLOSURES:

The study was funded by the Swedish Council for Health, Working Life and Welfare, Region Stockholm, the Swedish Society of Medicine, and Karolinska Institutet. Dr. de la Cruz received royalties for contributing articles to UpToDate and Wolters Kluwer Health and for editorial work from Elsevier outside the submitted work. See the paper for disclosures of the other authors.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Mental health comorbidities are prevalent among youth with overweight or obesity, with the strongest risk factors being male sex, older age, and extreme obesity.

METHODOLOGY:

• Researchers compared clinical characteristics and outcomes among children, adolescents, and young adults with overweight or obesity with or without a comorbid mental disorder who participated in a lifestyle intervention program.
• Overall, data from 114,248 individuals (age, 6-30 years; 53% females) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry were evaluated.
• Individuals were excluded if they had bariatric surgery or used weight-modifying drugs (metformin, orlistat, or glucagon-like peptide-1 analogues).
• Body mass index (BMI) was calculated as a standard deviation score (SDS) from a German youth population reference and was used to define overweight (90th to < 97th percentile), obesity (97th percentile), and severe obesity (≥ 99.5th percentile), which at age 18 correspond to adult cutoffs for overweight and obesity (25 kg/m² and 30 kg/m², respectively).
• Regression analysis identified the factors associated with mental disorders in those with overweight or obesity.

TAKEAWAY:

• A comorbid mental disorder was reported in 3969 individuals, with attention-deficit disorder (ADHD, 42.5%), anxiety (31.3%), depression (24.3%), and eating disorders (12.9%) being the most common.
• The factors most strongly associated with mental health comorbidity were male sex (odds ratio [OR], 1.39; 95% CI, 1.27-1.52), older age (OR, 1.42; 95% CI, 1.25-1.62), and severe obesity (OR, 1.45; 95% CI, 1.30-1.63).
• Mean BMI-SDS was higher in individuals with depression and eating disorders and lower in individuals with ADHD (both P < .001) than in those without mental disorders.
• Individuals with and without mental disorders benefited from similar BMI changes from lifestyle intervention programs.

IN PRACTICE:

The authors wrote, “Healthcare professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders, and regular mental health screening should be considered.”

SOURCE:

This study, led by Angela Galler from the Charité – Universitätsmedizin Berlin, Germany, was published online on January 9, 2024, in the International Journal of Obesity.

LIMITATIONS:

The study’s findings are based on data from a group of children, adolescents, and young adults with overweight or obesity treated in specialized obesity centers and may not be generalizable to all youth with obesity. Moreover, the study could not establish any conclusions regarding the cause or effect between obesity and mental disorders. Individuals were not tested psychologically for mental disorders and might have been underreported.

DISCLOSURES:

The manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which was funded by the Innovative Medicines Initiative 2 Joint Undertaking. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Mental health comorbidities are prevalent among youth with overweight or obesity, with the strongest risk factors being male sex, older age, and extreme obesity.

METHODOLOGY:

• Researchers compared clinical characteristics and outcomes among children, adolescents, and young adults with overweight or obesity with or without a comorbid mental disorder who participated in a lifestyle intervention program.
• Overall, data from 114,248 individuals (age, 6-30 years; 53% females) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry were evaluated.
• Individuals were excluded if they had bariatric surgery or used weight-modifying drugs (metformin, orlistat, or glucagon-like peptide-1 analogues).
• Body mass index (BMI) was calculated as a standard deviation score (SDS) from a German youth population reference and was used to define overweight (90th to < 97th percentile), obesity (97th percentile), and severe obesity (≥ 99.5th percentile), which at age 18 correspond to adult cutoffs for overweight and obesity (25 kg/m² and 30 kg/m², respectively).
• Regression analysis identified the factors associated with mental disorders in those with overweight or obesity.

TAKEAWAY:

• A comorbid mental disorder was reported in 3969 individuals, with attention-deficit disorder (ADHD, 42.5%), anxiety (31.3%), depression (24.3%), and eating disorders (12.9%) being the most common.
• The factors most strongly associated with mental health comorbidity were male sex (odds ratio [OR], 1.39; 95% CI, 1.27-1.52), older age (OR, 1.42; 95% CI, 1.25-1.62), and severe obesity (OR, 1.45; 95% CI, 1.30-1.63).
• Mean BMI-SDS was higher in individuals with depression and eating disorders and lower in individuals with ADHD (both P < .001) than in those without mental disorders.
• Individuals with and without mental disorders benefited from similar BMI changes from lifestyle intervention programs.

IN PRACTICE:

The authors wrote, “Healthcare professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders, and regular mental health screening should be considered.”

SOURCE:

This study, led by Angela Galler from the Charité – Universitätsmedizin Berlin, Germany, was published online on January 9, 2024, in the International Journal of Obesity.

LIMITATIONS:

The study’s findings are based on data from a group of children, adolescents, and young adults with overweight or obesity treated in specialized obesity centers and may not be generalizable to all youth with obesity. Moreover, the study could not establish any conclusions regarding the cause or effect between obesity and mental disorders. Individuals were not tested psychologically for mental disorders and might have been underreported.

DISCLOSURES:

The manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which was funded by the Innovative Medicines Initiative 2 Joint Undertaking. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Mental health comorbidities are prevalent among youth with overweight or obesity, with the strongest risk factors being male sex, older age, and extreme obesity.

METHODOLOGY:

• Researchers compared clinical characteristics and outcomes among children, adolescents, and young adults with overweight or obesity with or without a comorbid mental disorder who participated in a lifestyle intervention program.
• Overall, data from 114,248 individuals (age, 6-30 years; 53% females) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry were evaluated.
• Individuals were excluded if they had bariatric surgery or used weight-modifying drugs (metformin, orlistat, or glucagon-like peptide-1 analogues).
• Body mass index (BMI) was calculated as a standard deviation score (SDS) from a German youth population reference and was used to define overweight (90th to < 97th percentile), obesity (97th percentile), and severe obesity (≥ 99.5th percentile), which at age 18 correspond to adult cutoffs for overweight and obesity (25 kg/m² and 30 kg/m², respectively).
• Regression analysis identified the factors associated with mental disorders in those with overweight or obesity.

TAKEAWAY:

• A comorbid mental disorder was reported in 3969 individuals, with attention-deficit disorder (ADHD, 42.5%), anxiety (31.3%), depression (24.3%), and eating disorders (12.9%) being the most common.
• The factors most strongly associated with mental health comorbidity were male sex (odds ratio [OR], 1.39; 95% CI, 1.27-1.52), older age (OR, 1.42; 95% CI, 1.25-1.62), and severe obesity (OR, 1.45; 95% CI, 1.30-1.63).
• Mean BMI-SDS was higher in individuals with depression and eating disorders and lower in individuals with ADHD (both P < .001) than in those without mental disorders.
• Individuals with and without mental disorders benefited from similar BMI changes from lifestyle intervention programs.

IN PRACTICE:

The authors wrote, “Healthcare professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders, and regular mental health screening should be considered.”

SOURCE:

This study, led by Angela Galler from the Charité – Universitätsmedizin Berlin, Germany, was published online on January 9, 2024, in the International Journal of Obesity.

LIMITATIONS:

The study’s findings are based on data from a group of children, adolescents, and young adults with overweight or obesity treated in specialized obesity centers and may not be generalizable to all youth with obesity. Moreover, the study could not establish any conclusions regarding the cause or effect between obesity and mental disorders. Individuals were not tested psychologically for mental disorders and might have been underreported.

DISCLOSURES:

The manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which was funded by the Innovative Medicines Initiative 2 Joint Undertaking. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Neha Pathak, MD: Hello. Today, we’re talking to Dr. Daniel Clauw, a professor at the University of Michigan in Ann Arbor, who is running a major trial on treatments for chronic back pain. We’re talking today about managing back pain in the post-opioid world. Thank you so much, Dr. Clauw, for taking the time to be our resident pain consultant today. Managing chronic pain can lead to a large amount of burnout and helplessness in the clinic setting. That’s the reality with some of the modalities that patients are requesting; there is still confusion about what is optimal for a particular type of patient, this feeling that we’re not really helping people get better, and whenever patients come in, that’s always still their chief complaint.

How would you advise providers to think about that and to settle into their role as communicators about better strategies without the burnout?

Daniel Clauw, MD: The first thing is to broaden the number of other providers that you get involved in these individuals’ care as the evidence base for all of these nonpharmacologic therapies being effective in chronic pain increases and increases. As third-party payers begin to reimburse for more and more of these therapies, it’s really difficult to manage chronic pain patients if you’re trying to do it alone on an island.

If you can, identify the good physical therapists in your community that are going to really work with people to give them an exercise program that they can use at home; find a pain psychologist that can offer some cognitive-behavioral therapy (CBT) for insomnia and some CBT for pain; and in the subset of patients with trauma, give them the emotional awareness of the neural reprocessing therapy for that specific subset.

As you start to identify more and more of these nonpharmacologic therapies that you want your patients to try, each of those has a set of providers and they can be incredibly helpful so that you, as the primary care provider (PCP), don’t really feel overwhelmed that you’re it, that you’re the only one.

Many of these individuals have more time to spend, and they have more one-on-one in-person time than you do as a primary care physician in the current healthcare system. Many of those providers have become really good at doing amateur CBT, goal-setting, and some of the other things that you need to do when you manage chronic pain patients. Try to find that other group of people that you can send your patients to that are going to be offering some of these nonpharmacologic therapies, and they’ll really help you manage these individuals.

Dr. Pathak: I think a couple of things come up for me. One is that we have to maybe broaden thinking about pain management, not only as multimodal strategies but also as multidisciplinary strategies. To your point, I think that’s really important. I also worry and wonder about health equity concerns, because just as overburdened as many PCPs are, we’re seeing it’s very difficult to get into physical therapy or to get into a setting where you’d be able to receive CBT for your pain. Any thoughts on those types of considerations?

Dr. Clauw: That’s a huge problem. Our group and many other groups in the pain space are developing websites, smartphone apps, and things like that to try to get some of these things directly to individuals with pain, not only for the reasons that you stated but also so that persons with pain don’t have to become patients. Our healthcare systems often make pain worse rather than better.

There were some great articles in The Lancet about 5 years ago talking about low back pain and that in different countries, the healthcare systems, for different reasons, have a tendency to actually make low back pain worse because they do too much surgery, immobilize people, or things like that rather than just not make them better. I think we’ve overmedicalized chronic pain in some settings, and much of what we’re trying to lead people to are things that are parts of wellness programs. The NIH National Center for Complementary and Integrative Health director talks about whole person health often.

I think that these interdisciplinary, integrative approaches are what we have to be using for chronic pain patients. I tell pain patients that, among acupuncture, acupressure, mindfulness, five different forms of CBT, yoga, and tai chi, I don’t know which of those is going to work, but I know that about 1 in 3 individuals that tries each of those therapies gets a benefit. What I really should be doing most is incentivizing people and motivating people to keep trying some of those nonpharmacologic approaches that they haven’t yet tried, because when they find one that works for them, then they will integrate it into their day-to-day life.

The other trick I would use for primary care physicians or anyone managing chronic pain patients is, don’t try to incentivize a pain patient to go try a new nonpharmacologic therapy or start an exercise program because you want their pain score to go from a 6 to a 3. Incentivize them by asking them, what are two or three things that you’re not able to do now because you have chronic pain that you’d really like to be able to do?

You’d like to play nine holes of golf; you’d like to be able to hug your grandchild; or you’d like to be able to do something else. Use those functional goals that are patient0driven to motivate your patients to do these things, because that will work much better. Again, any of us are inherently more likely to take the time and the effort to do some of these nonpharmacologic therapies if it’s for a reason that internally motivates us.

Dr. Pathak: I think that’s great. I’m very privileged to work within the Veterans Affairs (VA) healthcare system. I think that there’s been a huge shift within VA healthcare to provide these ancillary services, whether it’s yoga, tai chi, or acupuncture, as an adjunct to the pain management strategy.

Also, what comes up for me, as you’re saying, is grounding the point that instead of relying on a pain score — which can be objective and different from patient to patient and even within a patient — we should choose a smart goal that is almost more objective when it’s functional. Your goal is to walk two blocks to the mailbox. Can we achieve that as part of your pain control strategy?

I so appreciate your taking the time to be our pain consultant today. I really appreciate our discussion, and I’d like to hand it over to you for any final thoughts.

Dr. Clauw: I’d add that when you’re seeing chronic pain patients, many of them are going to have comorbid sleep problems. They’re going to have comorbid problems with fatigue and memory problems, especially the central nervous system–driven forms of pain that we now call nociplastic pain. Look at those as therapeutic targets.

If you’re befuddled because you’ve tried many different things for pain in this individual you’ve been seeing for a while, focus on their sleep and focus on getting them more active. Don’t use the word exercise — because that scares chronic pain patients — but focus on getting them more active.

There are many different tactics and strategies that you can use to motivate the patients to try some of these new nonpharmacologic approaches as the evidence base continues to increase.

Dr. Pathak: Thank you so much, again, to Dr. Clauw for joining us and being our pain consultant, really helping us to think about managing back pain in the postopioid world.
 

Dr. Pathak is Chief Physician Editor, Health and Lifestyle Medicine, WebMD. She has disclosed no relevant financial relationships. Dr. Clauw is Director, Chronic Pain and Fatigue Research Center, Department of Anesthesia, University of Michigan, Ann Arbor. He disclosed ties with Tonix and Viatris.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Neha Pathak, MD: Hello. Today, we’re talking to Dr. Daniel Clauw, a professor at the University of Michigan in Ann Arbor, who is running a major trial on treatments for chronic back pain. We’re talking today about managing back pain in the post-opioid world. Thank you so much, Dr. Clauw, for taking the time to be our resident pain consultant today. Managing chronic pain can lead to a large amount of burnout and helplessness in the clinic setting. That’s the reality with some of the modalities that patients are requesting; there is still confusion about what is optimal for a particular type of patient, this feeling that we’re not really helping people get better, and whenever patients come in, that’s always still their chief complaint.

How would you advise providers to think about that and to settle into their role as communicators about better strategies without the burnout?

Daniel Clauw, MD: The first thing is to broaden the number of other providers that you get involved in these individuals’ care as the evidence base for all of these nonpharmacologic therapies being effective in chronic pain increases and increases. As third-party payers begin to reimburse for more and more of these therapies, it’s really difficult to manage chronic pain patients if you’re trying to do it alone on an island.

If you can, identify the good physical therapists in your community that are going to really work with people to give them an exercise program that they can use at home; find a pain psychologist that can offer some cognitive-behavioral therapy (CBT) for insomnia and some CBT for pain; and in the subset of patients with trauma, give them the emotional awareness of the neural reprocessing therapy for that specific subset.

As you start to identify more and more of these nonpharmacologic therapies that you want your patients to try, each of those has a set of providers and they can be incredibly helpful so that you, as the primary care provider (PCP), don’t really feel overwhelmed that you’re it, that you’re the only one.

Many of these individuals have more time to spend, and they have more one-on-one in-person time than you do as a primary care physician in the current healthcare system. Many of those providers have become really good at doing amateur CBT, goal-setting, and some of the other things that you need to do when you manage chronic pain patients. Try to find that other group of people that you can send your patients to that are going to be offering some of these nonpharmacologic therapies, and they’ll really help you manage these individuals.

Dr. Pathak: I think a couple of things come up for me. One is that we have to maybe broaden thinking about pain management, not only as multimodal strategies but also as multidisciplinary strategies. To your point, I think that’s really important. I also worry and wonder about health equity concerns, because just as overburdened as many PCPs are, we’re seeing it’s very difficult to get into physical therapy or to get into a setting where you’d be able to receive CBT for your pain. Any thoughts on those types of considerations?

Dr. Clauw: That’s a huge problem. Our group and many other groups in the pain space are developing websites, smartphone apps, and things like that to try to get some of these things directly to individuals with pain, not only for the reasons that you stated but also so that persons with pain don’t have to become patients. Our healthcare systems often make pain worse rather than better.

There were some great articles in The Lancet about 5 years ago talking about low back pain and that in different countries, the healthcare systems, for different reasons, have a tendency to actually make low back pain worse because they do too much surgery, immobilize people, or things like that rather than just not make them better. I think we’ve overmedicalized chronic pain in some settings, and much of what we’re trying to lead people to are things that are parts of wellness programs. The NIH National Center for Complementary and Integrative Health director talks about whole person health often.

I think that these interdisciplinary, integrative approaches are what we have to be using for chronic pain patients. I tell pain patients that, among acupuncture, acupressure, mindfulness, five different forms of CBT, yoga, and tai chi, I don’t know which of those is going to work, but I know that about 1 in 3 individuals that tries each of those therapies gets a benefit. What I really should be doing most is incentivizing people and motivating people to keep trying some of those nonpharmacologic approaches that they haven’t yet tried, because when they find one that works for them, then they will integrate it into their day-to-day life.

The other trick I would use for primary care physicians or anyone managing chronic pain patients is, don’t try to incentivize a pain patient to go try a new nonpharmacologic therapy or start an exercise program because you want their pain score to go from a 6 to a 3. Incentivize them by asking them, what are two or three things that you’re not able to do now because you have chronic pain that you’d really like to be able to do?

You’d like to play nine holes of golf; you’d like to be able to hug your grandchild; or you’d like to be able to do something else. Use those functional goals that are patient0driven to motivate your patients to do these things, because that will work much better. Again, any of us are inherently more likely to take the time and the effort to do some of these nonpharmacologic therapies if it’s for a reason that internally motivates us.

Dr. Pathak: I think that’s great. I’m very privileged to work within the Veterans Affairs (VA) healthcare system. I think that there’s been a huge shift within VA healthcare to provide these ancillary services, whether it’s yoga, tai chi, or acupuncture, as an adjunct to the pain management strategy.

Also, what comes up for me, as you’re saying, is grounding the point that instead of relying on a pain score — which can be objective and different from patient to patient and even within a patient — we should choose a smart goal that is almost more objective when it’s functional. Your goal is to walk two blocks to the mailbox. Can we achieve that as part of your pain control strategy?

I so appreciate your taking the time to be our pain consultant today. I really appreciate our discussion, and I’d like to hand it over to you for any final thoughts.

Dr. Clauw: I’d add that when you’re seeing chronic pain patients, many of them are going to have comorbid sleep problems. They’re going to have comorbid problems with fatigue and memory problems, especially the central nervous system–driven forms of pain that we now call nociplastic pain. Look at those as therapeutic targets.

If you’re befuddled because you’ve tried many different things for pain in this individual you’ve been seeing for a while, focus on their sleep and focus on getting them more active. Don’t use the word exercise — because that scares chronic pain patients — but focus on getting them more active.

There are many different tactics and strategies that you can use to motivate the patients to try some of these new nonpharmacologic approaches as the evidence base continues to increase.

Dr. Pathak: Thank you so much, again, to Dr. Clauw for joining us and being our pain consultant, really helping us to think about managing back pain in the postopioid world.
 

Dr. Pathak is Chief Physician Editor, Health and Lifestyle Medicine, WebMD. She has disclosed no relevant financial relationships. Dr. Clauw is Director, Chronic Pain and Fatigue Research Center, Department of Anesthesia, University of Michigan, Ann Arbor. He disclosed ties with Tonix and Viatris.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Neha Pathak, MD: Hello. Today, we’re talking to Dr. Daniel Clauw, a professor at the University of Michigan in Ann Arbor, who is running a major trial on treatments for chronic back pain. We’re talking today about managing back pain in the post-opioid world. Thank you so much, Dr. Clauw, for taking the time to be our resident pain consultant today. Managing chronic pain can lead to a large amount of burnout and helplessness in the clinic setting. That’s the reality with some of the modalities that patients are requesting; there is still confusion about what is optimal for a particular type of patient, this feeling that we’re not really helping people get better, and whenever patients come in, that’s always still their chief complaint.

How would you advise providers to think about that and to settle into their role as communicators about better strategies without the burnout?

Daniel Clauw, MD: The first thing is to broaden the number of other providers that you get involved in these individuals’ care as the evidence base for all of these nonpharmacologic therapies being effective in chronic pain increases and increases. As third-party payers begin to reimburse for more and more of these therapies, it’s really difficult to manage chronic pain patients if you’re trying to do it alone on an island.

If you can, identify the good physical therapists in your community that are going to really work with people to give them an exercise program that they can use at home; find a pain psychologist that can offer some cognitive-behavioral therapy (CBT) for insomnia and some CBT for pain; and in the subset of patients with trauma, give them the emotional awareness of the neural reprocessing therapy for that specific subset.

As you start to identify more and more of these nonpharmacologic therapies that you want your patients to try, each of those has a set of providers and they can be incredibly helpful so that you, as the primary care provider (PCP), don’t really feel overwhelmed that you’re it, that you’re the only one.

Many of these individuals have more time to spend, and they have more one-on-one in-person time than you do as a primary care physician in the current healthcare system. Many of those providers have become really good at doing amateur CBT, goal-setting, and some of the other things that you need to do when you manage chronic pain patients. Try to find that other group of people that you can send your patients to that are going to be offering some of these nonpharmacologic therapies, and they’ll really help you manage these individuals.

Dr. Pathak: I think a couple of things come up for me. One is that we have to maybe broaden thinking about pain management, not only as multimodal strategies but also as multidisciplinary strategies. To your point, I think that’s really important. I also worry and wonder about health equity concerns, because just as overburdened as many PCPs are, we’re seeing it’s very difficult to get into physical therapy or to get into a setting where you’d be able to receive CBT for your pain. Any thoughts on those types of considerations?

Dr. Clauw: That’s a huge problem. Our group and many other groups in the pain space are developing websites, smartphone apps, and things like that to try to get some of these things directly to individuals with pain, not only for the reasons that you stated but also so that persons with pain don’t have to become patients. Our healthcare systems often make pain worse rather than better.

There were some great articles in The Lancet about 5 years ago talking about low back pain and that in different countries, the healthcare systems, for different reasons, have a tendency to actually make low back pain worse because they do too much surgery, immobilize people, or things like that rather than just not make them better. I think we’ve overmedicalized chronic pain in some settings, and much of what we’re trying to lead people to are things that are parts of wellness programs. The NIH National Center for Complementary and Integrative Health director talks about whole person health often.

I think that these interdisciplinary, integrative approaches are what we have to be using for chronic pain patients. I tell pain patients that, among acupuncture, acupressure, mindfulness, five different forms of CBT, yoga, and tai chi, I don’t know which of those is going to work, but I know that about 1 in 3 individuals that tries each of those therapies gets a benefit. What I really should be doing most is incentivizing people and motivating people to keep trying some of those nonpharmacologic approaches that they haven’t yet tried, because when they find one that works for them, then they will integrate it into their day-to-day life.

The other trick I would use for primary care physicians or anyone managing chronic pain patients is, don’t try to incentivize a pain patient to go try a new nonpharmacologic therapy or start an exercise program because you want their pain score to go from a 6 to a 3. Incentivize them by asking them, what are two or three things that you’re not able to do now because you have chronic pain that you’d really like to be able to do?

You’d like to play nine holes of golf; you’d like to be able to hug your grandchild; or you’d like to be able to do something else. Use those functional goals that are patient0driven to motivate your patients to do these things, because that will work much better. Again, any of us are inherently more likely to take the time and the effort to do some of these nonpharmacologic therapies if it’s for a reason that internally motivates us.

Dr. Pathak: I think that’s great. I’m very privileged to work within the Veterans Affairs (VA) healthcare system. I think that there’s been a huge shift within VA healthcare to provide these ancillary services, whether it’s yoga, tai chi, or acupuncture, as an adjunct to the pain management strategy.

Also, what comes up for me, as you’re saying, is grounding the point that instead of relying on a pain score — which can be objective and different from patient to patient and even within a patient — we should choose a smart goal that is almost more objective when it’s functional. Your goal is to walk two blocks to the mailbox. Can we achieve that as part of your pain control strategy?

I so appreciate your taking the time to be our pain consultant today. I really appreciate our discussion, and I’d like to hand it over to you for any final thoughts.

Dr. Clauw: I’d add that when you’re seeing chronic pain patients, many of them are going to have comorbid sleep problems. They’re going to have comorbid problems with fatigue and memory problems, especially the central nervous system–driven forms of pain that we now call nociplastic pain. Look at those as therapeutic targets.

If you’re befuddled because you’ve tried many different things for pain in this individual you’ve been seeing for a while, focus on their sleep and focus on getting them more active. Don’t use the word exercise — because that scares chronic pain patients — but focus on getting them more active.

There are many different tactics and strategies that you can use to motivate the patients to try some of these new nonpharmacologic approaches as the evidence base continues to increase.

Dr. Pathak: Thank you so much, again, to Dr. Clauw for joining us and being our pain consultant, really helping us to think about managing back pain in the postopioid world.
 

Dr. Pathak is Chief Physician Editor, Health and Lifestyle Medicine, WebMD. She has disclosed no relevant financial relationships. Dr. Clauw is Director, Chronic Pain and Fatigue Research Center, Department of Anesthesia, University of Michigan, Ann Arbor. He disclosed ties with Tonix and Viatris.

A version of this article appeared on Medscape.com.

In a recent issue of Pediatric News, the Child Psychiatry Consult column featured an excellent discussion by Dr. David Rettew of some new research into a possible association between excessive crying in infancy and emotional problems later in childhood. This longitudinal study of almost 5,000 children included an assessment at 3 months and an MRI at age 10, which found that the infants who were excessive criers also had smaller amygdala. While the orders of magnitude of the researchers’ observations is small, it is interesting that the mothers of excessive criers were slightly more likely to experience mental health problems.

Dr. Rettew wisely cautions us to take note of this study’s findings but avoid overreacting. If indeed excessive crying in infancy is a marker for future problems, at the moment we may want to increase our efforts in helping parents improve their parenting skills using a nonjudgmental approach.

Using Dr. Rettew’s sage advice as a leaping off point, I will add the reminder that we must continue to meet head on the venerable myth that “colic” is a gastrointestinal problem. We must promise to never code out a parental complaint as “colic.” If we want to label it “excessive crying of infancy,” that’s one thing, but using “colic” only serves to perpetuate the myth and all the old, and sometimes dangerous, remedies that continue to cling to it.

Whether we use the term “colicky behavior” or call it “excessive crying,” we must remember these are merely descriptive terms. We have not made a diagnosis and are obligated to keep our minds open to serious and life-threatening conditions that make infants cry excessively — aberrant coronary arteries and urinary obstructions to name just two.

I can’t leave the phenomenon of colic without adding a nickel to the two cents I have already gifted you. When I was in medical school, I am sure I was told something about the amygdala. But, I suspect that I was only expected to recall where it lived. In the 50+ years since that brief encounter, other folks have learned much more. Prompted by this study, I searched what is known about small amygdala. Turns out that sleep deprivation has been associated with smaller amygdala, as has episodic migraine headaches, both in adults.

Regular readers of Letters from Maine can already smell where this is going. For decades I have believed that both excessive crying in infancy and episodic migraine in children are associated with, and my bias would say “caused” by, sleep deprivation. We learned from this study that mothers of excessively crying infants are more likely to have mental health problems. And, I will add that at least one study has shown that mothers and fathers of excessively crying infants are more likely to suffer from migraines.

Whether you join me in my biased interpretation isn’t important. What this study tells us is that there is likely to be something going on in infancy that may be a marker for future mental health problems. Were these children born with small or vulnerable amygdala? Did poor sleep hygiene contribute to the problem by interfering with the growth of their amygdala? I can envision studies that could provide some clarity. I’m not sure many parents would agree to have their happy and well-slept 3-month-olds slid into an MRI tube to serve as controls. But, I wouldn’t be surprised that we could find a sizable number of sleep deprived and frazzled parents of colicky infants who would agree if we told them it might help find an answer.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In a recent issue of Pediatric News, the Child Psychiatry Consult column featured an excellent discussion by Dr. David Rettew of some new research into a possible association between excessive crying in infancy and emotional problems later in childhood. This longitudinal study of almost 5,000 children included an assessment at 3 months and an MRI at age 10, which found that the infants who were excessive criers also had smaller amygdala. While the orders of magnitude of the researchers’ observations is small, it is interesting that the mothers of excessive criers were slightly more likely to experience mental health problems.

Dr. Rettew wisely cautions us to take note of this study’s findings but avoid overreacting. If indeed excessive crying in infancy is a marker for future problems, at the moment we may want to increase our efforts in helping parents improve their parenting skills using a nonjudgmental approach.

Using Dr. Rettew’s sage advice as a leaping off point, I will add the reminder that we must continue to meet head on the venerable myth that “colic” is a gastrointestinal problem. We must promise to never code out a parental complaint as “colic.” If we want to label it “excessive crying of infancy,” that’s one thing, but using “colic” only serves to perpetuate the myth and all the old, and sometimes dangerous, remedies that continue to cling to it.

Whether we use the term “colicky behavior” or call it “excessive crying,” we must remember these are merely descriptive terms. We have not made a diagnosis and are obligated to keep our minds open to serious and life-threatening conditions that make infants cry excessively — aberrant coronary arteries and urinary obstructions to name just two.

I can’t leave the phenomenon of colic without adding a nickel to the two cents I have already gifted you. When I was in medical school, I am sure I was told something about the amygdala. But, I suspect that I was only expected to recall where it lived. In the 50+ years since that brief encounter, other folks have learned much more. Prompted by this study, I searched what is known about small amygdala. Turns out that sleep deprivation has been associated with smaller amygdala, as has episodic migraine headaches, both in adults.

Regular readers of Letters from Maine can already smell where this is going. For decades I have believed that both excessive crying in infancy and episodic migraine in children are associated with, and my bias would say “caused” by, sleep deprivation. We learned from this study that mothers of excessively crying infants are more likely to have mental health problems. And, I will add that at least one study has shown that mothers and fathers of excessively crying infants are more likely to suffer from migraines.

Whether you join me in my biased interpretation isn’t important. What this study tells us is that there is likely to be something going on in infancy that may be a marker for future mental health problems. Were these children born with small or vulnerable amygdala? Did poor sleep hygiene contribute to the problem by interfering with the growth of their amygdala? I can envision studies that could provide some clarity. I’m not sure many parents would agree to have their happy and well-slept 3-month-olds slid into an MRI tube to serve as controls. But, I wouldn’t be surprised that we could find a sizable number of sleep deprived and frazzled parents of colicky infants who would agree if we told them it might help find an answer.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In a recent issue of Pediatric News, the Child Psychiatry Consult column featured an excellent discussion by Dr. David Rettew of some new research into a possible association between excessive crying in infancy and emotional problems later in childhood. This longitudinal study of almost 5,000 children included an assessment at 3 months and an MRI at age 10, which found that the infants who were excessive criers also had smaller amygdala. While the orders of magnitude of the researchers’ observations is small, it is interesting that the mothers of excessive criers were slightly more likely to experience mental health problems.

Dr. Rettew wisely cautions us to take note of this study’s findings but avoid overreacting. If indeed excessive crying in infancy is a marker for future problems, at the moment we may want to increase our efforts in helping parents improve their parenting skills using a nonjudgmental approach.

Using Dr. Rettew’s sage advice as a leaping off point, I will add the reminder that we must continue to meet head on the venerable myth that “colic” is a gastrointestinal problem. We must promise to never code out a parental complaint as “colic.” If we want to label it “excessive crying of infancy,” that’s one thing, but using “colic” only serves to perpetuate the myth and all the old, and sometimes dangerous, remedies that continue to cling to it.

Whether we use the term “colicky behavior” or call it “excessive crying,” we must remember these are merely descriptive terms. We have not made a diagnosis and are obligated to keep our minds open to serious and life-threatening conditions that make infants cry excessively — aberrant coronary arteries and urinary obstructions to name just two.

I can’t leave the phenomenon of colic without adding a nickel to the two cents I have already gifted you. When I was in medical school, I am sure I was told something about the amygdala. But, I suspect that I was only expected to recall where it lived. In the 50+ years since that brief encounter, other folks have learned much more. Prompted by this study, I searched what is known about small amygdala. Turns out that sleep deprivation has been associated with smaller amygdala, as has episodic migraine headaches, both in adults.

Regular readers of Letters from Maine can already smell where this is going. For decades I have believed that both excessive crying in infancy and episodic migraine in children are associated with, and my bias would say “caused” by, sleep deprivation. We learned from this study that mothers of excessively crying infants are more likely to have mental health problems. And, I will add that at least one study has shown that mothers and fathers of excessively crying infants are more likely to suffer from migraines.

Whether you join me in my biased interpretation isn’t important. What this study tells us is that there is likely to be something going on in infancy that may be a marker for future mental health problems. Were these children born with small or vulnerable amygdala? Did poor sleep hygiene contribute to the problem by interfering with the growth of their amygdala? I can envision studies that could provide some clarity. I’m not sure many parents would agree to have their happy and well-slept 3-month-olds slid into an MRI tube to serve as controls. But, I wouldn’t be surprised that we could find a sizable number of sleep deprived and frazzled parents of colicky infants who would agree if we told them it might help find an answer.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows.

This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.

The study was published online on January 23, 2024, in JAMA. 
 

Mental Health Harm

In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.

The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.

The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). 

In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.

Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.

Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. 
 

Implications for Care 

In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”

These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.

“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added. 

The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.

A version of this article appeared on Medscape.com.

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows.

This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.

The study was published online on January 23, 2024, in JAMA. 
 

Mental Health Harm

In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.

The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.

The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). 

In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.

Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.

Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. 
 

Implications for Care 

In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”

These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.

“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added. 

The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.

A version of this article appeared on Medscape.com.

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows.

This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.

The study was published online on January 23, 2024, in JAMA. 
 

Mental Health Harm

In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.

The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.

The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). 

In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.

Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.

Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. 
 

Implications for Care 

In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”

These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.

“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added. 

The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.

A version of this article appeared on Medscape.com.

Adults with posttraumatic stress disorder (PTSD) have smaller cerebellums than unaffected adults, suggesting that this part of the brain may be a potential therapeutic target.

According to recent research on more than 4000 adults, cerebellum volume was significantly smaller (by about 2%) in those with PTSD than in trauma-exposed and trauma-naive controls without PTSD.

“The differences were largely within the posterior lobe, where a lot of the more cognitive functions attributed to the cerebellum seem to localize, as well as the vermis, which is linked to a lot of emotional processing functions,” lead author Ashley Huggins, PhD, said in a news release.

“If we know what areas are implicated, then we can start to focus interventions like brain stimulation on the cerebellum and potentially improve treatment outcomes,” said Dr. Huggins, who worked on the study while a postdoctoral researcher in the lab of Rajendra A. Morey, MD, at Duke University, Durham, North Carolina, and is now at the University of Arizona, Tucson.

While the cerebellum is known for its role in coordinating movement and balance, it also plays a key role in emotions and memory, which are affected by PTSD.

Smaller cerebellar volume has been observed in some adult and pediatric populations with PTSD.

However, those studies have been limited by either small sample sizes, the failure to consider key neuroanatomical subdivisions of the cerebellum, or a focus on certain populations such as veterans of sexual assault victims with PTSD.

To overcome these limitations, the researchers conducted a mega-analysis of total and subregional cerebellar volumes in a large, multicohort dataset from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Psychiatric Genomics Consortium PTSD workgroup that was published online on January 10, 2024, in Molecular Psychiatry.

They employed a novel, standardized ENIGMA cerebellum parcellation protocol to quantify cerebellar lobule volumes using structural MRI data from 1642 adults with PTSD and 2573 healthy controls without PTSD (88% trauma-exposed and 12% trauma-naive).

After adjustment for age, gender, and total intracranial volume, PTSD was associated with significant gray and white matter reductions of the cerebellum.

People with PTSD demonstrated smaller total cerebellum volume as well as reduced volume in subregions primarily within the posterior cerebellum, vermis, and flocculonodular cerebellum than controls.

In general, PTSD severity was more robustly associated with cerebellar volume differences than PTSD diagnosis.

Focusing purely on a “yes-or-no” categorical diagnosis didn’t always provide the clearest picture. “When we looked at PTSD severity, people who had more severe forms of the disorder had an even smaller cerebellar volume,” Dr. Huggins explained in the news release.

Novel Treatment Target

These findings add to “an emerging literature that underscores the relevance of cerebellar structure in the pathophysiology of PTSD,” the researchers noted.

They caution that despite the significant findings suggesting associations between PTSD and smaller cerebellar volumes, effect sizes were small. “As such, it is unlikely that structural cerebellar volumes alone will provide a clinically useful biomarker (eg, for individual-level prediction).”

Nonetheless, the study highlights the cerebellum as a “novel treatment target that may be leveraged to improve treatment outcomes for PTSD,” they wrote.

They noted that prior work has shown that the cerebellum is sensitive to external modulation. For example, noninvasive brain stimulation of the cerebellum has been shown to modulate cognitive, emotional, and social processes commonly disrupted in PTSD.

Commenting on this research, Cyrus A. Raji, MD, PhD, associate professor of radiology and neurology at Washington University in St. Louis, noted that this “large neuroimaging study links PTSD to cerebellar volume loss.”

“However, PTSD and traumatic brain injury frequently co-occur, and PTSD also frequently arises after TBI. Additionally, TBI is strongly linked to cerebellar volume loss,” Dr. Raji pointed out.

“Future studies need to better delineate volume loss from these conditions, especially when they are comorbid, though the expectation is these effects would be additive with TBI being the initial and most severe driving force,” Dr. Raji added.

The research had no commercial funding. Author disclosures are listed with the original article. Dr. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution Medicine LLC.
 

A version of this article appears on Medscape.com.

Adults with posttraumatic stress disorder (PTSD) have smaller cerebellums than unaffected adults, suggesting that this part of the brain may be a potential therapeutic target.

According to recent research on more than 4000 adults, cerebellum volume was significantly smaller (by about 2%) in those with PTSD than in trauma-exposed and trauma-naive controls without PTSD.

“The differences were largely within the posterior lobe, where a lot of the more cognitive functions attributed to the cerebellum seem to localize, as well as the vermis, which is linked to a lot of emotional processing functions,” lead author Ashley Huggins, PhD, said in a news release.

“If we know what areas are implicated, then we can start to focus interventions like brain stimulation on the cerebellum and potentially improve treatment outcomes,” said Dr. Huggins, who worked on the study while a postdoctoral researcher in the lab of Rajendra A. Morey, MD, at Duke University, Durham, North Carolina, and is now at the University of Arizona, Tucson.

While the cerebellum is known for its role in coordinating movement and balance, it also plays a key role in emotions and memory, which are affected by PTSD.

Smaller cerebellar volume has been observed in some adult and pediatric populations with PTSD.

However, those studies have been limited by either small sample sizes, the failure to consider key neuroanatomical subdivisions of the cerebellum, or a focus on certain populations such as veterans of sexual assault victims with PTSD.

To overcome these limitations, the researchers conducted a mega-analysis of total and subregional cerebellar volumes in a large, multicohort dataset from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Psychiatric Genomics Consortium PTSD workgroup that was published online on January 10, 2024, in Molecular Psychiatry.

They employed a novel, standardized ENIGMA cerebellum parcellation protocol to quantify cerebellar lobule volumes using structural MRI data from 1642 adults with PTSD and 2573 healthy controls without PTSD (88% trauma-exposed and 12% trauma-naive).

After adjustment for age, gender, and total intracranial volume, PTSD was associated with significant gray and white matter reductions of the cerebellum.

People with PTSD demonstrated smaller total cerebellum volume as well as reduced volume in subregions primarily within the posterior cerebellum, vermis, and flocculonodular cerebellum than controls.

In general, PTSD severity was more robustly associated with cerebellar volume differences than PTSD diagnosis.

Focusing purely on a “yes-or-no” categorical diagnosis didn’t always provide the clearest picture. “When we looked at PTSD severity, people who had more severe forms of the disorder had an even smaller cerebellar volume,” Dr. Huggins explained in the news release.

Novel Treatment Target

These findings add to “an emerging literature that underscores the relevance of cerebellar structure in the pathophysiology of PTSD,” the researchers noted.

They caution that despite the significant findings suggesting associations between PTSD and smaller cerebellar volumes, effect sizes were small. “As such, it is unlikely that structural cerebellar volumes alone will provide a clinically useful biomarker (eg, for individual-level prediction).”

Nonetheless, the study highlights the cerebellum as a “novel treatment target that may be leveraged to improve treatment outcomes for PTSD,” they wrote.

They noted that prior work has shown that the cerebellum is sensitive to external modulation. For example, noninvasive brain stimulation of the cerebellum has been shown to modulate cognitive, emotional, and social processes commonly disrupted in PTSD.

Commenting on this research, Cyrus A. Raji, MD, PhD, associate professor of radiology and neurology at Washington University in St. Louis, noted that this “large neuroimaging study links PTSD to cerebellar volume loss.”

“However, PTSD and traumatic brain injury frequently co-occur, and PTSD also frequently arises after TBI. Additionally, TBI is strongly linked to cerebellar volume loss,” Dr. Raji pointed out.

“Future studies need to better delineate volume loss from these conditions, especially when they are comorbid, though the expectation is these effects would be additive with TBI being the initial and most severe driving force,” Dr. Raji added.

The research had no commercial funding. Author disclosures are listed with the original article. Dr. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution Medicine LLC.
 

A version of this article appears on Medscape.com.

Adults with posttraumatic stress disorder (PTSD) have smaller cerebellums than unaffected adults, suggesting that this part of the brain may be a potential therapeutic target.

According to recent research on more than 4000 adults, cerebellum volume was significantly smaller (by about 2%) in those with PTSD than in trauma-exposed and trauma-naive controls without PTSD.

“The differences were largely within the posterior lobe, where a lot of the more cognitive functions attributed to the cerebellum seem to localize, as well as the vermis, which is linked to a lot of emotional processing functions,” lead author Ashley Huggins, PhD, said in a news release.

“If we know what areas are implicated, then we can start to focus interventions like brain stimulation on the cerebellum and potentially improve treatment outcomes,” said Dr. Huggins, who worked on the study while a postdoctoral researcher in the lab of Rajendra A. Morey, MD, at Duke University, Durham, North Carolina, and is now at the University of Arizona, Tucson.

While the cerebellum is known for its role in coordinating movement and balance, it also plays a key role in emotions and memory, which are affected by PTSD.

Smaller cerebellar volume has been observed in some adult and pediatric populations with PTSD.

However, those studies have been limited by either small sample sizes, the failure to consider key neuroanatomical subdivisions of the cerebellum, or a focus on certain populations such as veterans of sexual assault victims with PTSD.

To overcome these limitations, the researchers conducted a mega-analysis of total and subregional cerebellar volumes in a large, multicohort dataset from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Psychiatric Genomics Consortium PTSD workgroup that was published online on January 10, 2024, in Molecular Psychiatry.

They employed a novel, standardized ENIGMA cerebellum parcellation protocol to quantify cerebellar lobule volumes using structural MRI data from 1642 adults with PTSD and 2573 healthy controls without PTSD (88% trauma-exposed and 12% trauma-naive).

After adjustment for age, gender, and total intracranial volume, PTSD was associated with significant gray and white matter reductions of the cerebellum.

People with PTSD demonstrated smaller total cerebellum volume as well as reduced volume in subregions primarily within the posterior cerebellum, vermis, and flocculonodular cerebellum than controls.

In general, PTSD severity was more robustly associated with cerebellar volume differences than PTSD diagnosis.

Focusing purely on a “yes-or-no” categorical diagnosis didn’t always provide the clearest picture. “When we looked at PTSD severity, people who had more severe forms of the disorder had an even smaller cerebellar volume,” Dr. Huggins explained in the news release.

Novel Treatment Target

These findings add to “an emerging literature that underscores the relevance of cerebellar structure in the pathophysiology of PTSD,” the researchers noted.

They caution that despite the significant findings suggesting associations between PTSD and smaller cerebellar volumes, effect sizes were small. “As such, it is unlikely that structural cerebellar volumes alone will provide a clinically useful biomarker (eg, for individual-level prediction).”

Nonetheless, the study highlights the cerebellum as a “novel treatment target that may be leveraged to improve treatment outcomes for PTSD,” they wrote.

They noted that prior work has shown that the cerebellum is sensitive to external modulation. For example, noninvasive brain stimulation of the cerebellum has been shown to modulate cognitive, emotional, and social processes commonly disrupted in PTSD.

Commenting on this research, Cyrus A. Raji, MD, PhD, associate professor of radiology and neurology at Washington University in St. Louis, noted that this “large neuroimaging study links PTSD to cerebellar volume loss.”

“However, PTSD and traumatic brain injury frequently co-occur, and PTSD also frequently arises after TBI. Additionally, TBI is strongly linked to cerebellar volume loss,” Dr. Raji pointed out.

“Future studies need to better delineate volume loss from these conditions, especially when they are comorbid, though the expectation is these effects would be additive with TBI being the initial and most severe driving force,” Dr. Raji added.

The research had no commercial funding. Author disclosures are listed with the original article. Dr. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution Medicine LLC.
 

A version of this article appears on Medscape.com.