Chronotherapeutic intervention targeting emotion regulation brain circuitry, symptoms, and suicide risk in adolescents and young adults with bipolar disorder: a pilot randomised trial

Background Mood episodes and high suicide risk of bipolar disorder (BD) are thought to derive from amygdala–ventral prefrontal cortex emotion regulation brain circuitry dysfunction and resulting emotion dysregulation, making these potential intervention targets.Objective To assess feasibility, accep...

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Main Authors: Jihoon A Kim, Anjali Sankar, Rebecca Marks, Erin Carrubba, Bernadette Lecza, Susan Quatrano, Linda Spencer, R. Todd Constable, Brian Pittman, Eli R Lebowitz, Wendy K Silverman, Holly A Swartz, Hilary P Blumberg
Format: Article
Language:English
Published: BMJ Publishing Group 2025-02-01
Series:BMJ Mental Health
Online Access:https://mentalhealth.bmj.com/content/28/1/e301338.full
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author Jihoon A Kim
Anjali Sankar
Rebecca Marks
Erin Carrubba
Bernadette Lecza
Susan Quatrano
Linda Spencer
R. Todd Constable
Brian Pittman
Eli R Lebowitz
Wendy K Silverman
Holly A Swartz
Hilary P Blumberg
author_facet Jihoon A Kim
Anjali Sankar
Rebecca Marks
Erin Carrubba
Bernadette Lecza
Susan Quatrano
Linda Spencer
R. Todd Constable
Brian Pittman
Eli R Lebowitz
Wendy K Silverman
Holly A Swartz
Hilary P Blumberg
author_sort Jihoon A Kim
collection DOAJ
description Background Mood episodes and high suicide risk of bipolar disorder (BD) are thought to derive from amygdala–ventral prefrontal cortex emotion regulation brain circuitry dysfunction and resulting emotion dysregulation, making these potential intervention targets.Objective To assess feasibility, acceptability, and preliminary efficacy in engaging the emotion regulation targets of two Brain Emotion Circuitry-targeted Self-Monitoring and Regulation Therapy (BE-SMART) variations in adolescents and young adults with BD (BDAYA): BE-SMART-ER, which directly targets emotion regulation, and BE-SMART-DR, a social rhythm therapy (SRT)-based chronotherapeutic intervention designed to reduce daily rhythm (DR) irregularities.Methods In a single-blind, parallel, pilot-randomised trial, 60 BDAYA (aged 16–29 years) were randomised to 12 weekly sessions (9 telehealth) of BE-SMART-DR or BE-SMART-ER. Nineteen BE-SMART-DR and 16 BE-SMART-ER participants completed the intervention, with 11 and 13, respectively, having pre-intervention and post-intervention functional MRI data.Findings In addition to demonstrating feasibility, only BE-SMART-DR showed pre-treatment to post-treatment improvements in DR regularity (Cohen’s d=0.55; 95% CI [0.06, 1.03]), associated with reductions in left amygdala responses to emotional face stimuli (pFWE (family-wise error)-SVC (small volume correction)<0.05), difficulties in emotion regulation (d=0.75; 95% CI [0.23, 1.25]) and suicide risk (d=0.65; 95% CI [0.15, 1.14]). Significant correlations were observed among these changes (p<0.05). Both interventions showed high acceptability and improvements in depression and mania symptoms. No intervention-related adverse events were observed.Conclusions Regularising DRs may enhance emotion regulation brain circuitry functioning, emotion regulation, and reduce suicide risk in BDAYA.Clinical implications Chronotherapeutic interventions regularising DRs, such as SRT, should be studied further as potential treatment strategies for BDAYA.Trial registration number NCT03183388.
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spelling doaj-art-060f5a63df1e4538bb8257dffb3f8dc72025-08-20T03:00:50ZengBMJ Publishing GroupBMJ Mental Health2755-97342025-02-0128110.1136/bmjment-2024-301338Chronotherapeutic intervention targeting emotion regulation brain circuitry, symptoms, and suicide risk in adolescents and young adults with bipolar disorder: a pilot randomised trialJihoon A Kim0Anjali Sankar1Rebecca Marks2Erin Carrubba3Bernadette Lecza4Susan Quatrano5Linda Spencer6R. Todd Constable7Brian Pittman8Eli R Lebowitz9Wendy K Silverman10Holly A Swartz11Hilary P Blumberg12Psychiatry, Yale School of Medicine, New Haven, Connecticut, USANeurobiology Research Unit, Copenhagen University Hospital, Kobenhavn, DenmarkPsychiatry, Yale School of Medicine, New Haven, Connecticut, USAPsychiatry, Yale School of Medicine, New Haven, Connecticut, USAPsychiatry, Yale School of Medicine, New Haven, Connecticut, USAPsychiatry, Yale School of Medicine, New Haven, Connecticut, USAPsychiatry, Yale School of Medicine, New Haven, Connecticut, USAPsychiatry, Yale School of Medicine, New Haven, Connecticut, USAPsychiatry, Yale School of Medicine, New Haven, Connecticut, USAChild Study Center, Yale School of Medicine, New Haven, Connecticut, USAPsychiatry and Child Study Center, Yale School of Medicine, New Haven, Connecticut, USAPsychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USAPsychiatry, Radiology and Biomedical Imaging, and Child Study Center, Yale School of Medicine, New Haven, Connecticut, USABackground Mood episodes and high suicide risk of bipolar disorder (BD) are thought to derive from amygdala–ventral prefrontal cortex emotion regulation brain circuitry dysfunction and resulting emotion dysregulation, making these potential intervention targets.Objective To assess feasibility, acceptability, and preliminary efficacy in engaging the emotion regulation targets of two Brain Emotion Circuitry-targeted Self-Monitoring and Regulation Therapy (BE-SMART) variations in adolescents and young adults with BD (BDAYA): BE-SMART-ER, which directly targets emotion regulation, and BE-SMART-DR, a social rhythm therapy (SRT)-based chronotherapeutic intervention designed to reduce daily rhythm (DR) irregularities.Methods In a single-blind, parallel, pilot-randomised trial, 60 BDAYA (aged 16–29 years) were randomised to 12 weekly sessions (9 telehealth) of BE-SMART-DR or BE-SMART-ER. Nineteen BE-SMART-DR and 16 BE-SMART-ER participants completed the intervention, with 11 and 13, respectively, having pre-intervention and post-intervention functional MRI data.Findings In addition to demonstrating feasibility, only BE-SMART-DR showed pre-treatment to post-treatment improvements in DR regularity (Cohen’s d=0.55; 95% CI [0.06, 1.03]), associated with reductions in left amygdala responses to emotional face stimuli (pFWE (family-wise error)-SVC (small volume correction)<0.05), difficulties in emotion regulation (d=0.75; 95% CI [0.23, 1.25]) and suicide risk (d=0.65; 95% CI [0.15, 1.14]). Significant correlations were observed among these changes (p<0.05). Both interventions showed high acceptability and improvements in depression and mania symptoms. No intervention-related adverse events were observed.Conclusions Regularising DRs may enhance emotion regulation brain circuitry functioning, emotion regulation, and reduce suicide risk in BDAYA.Clinical implications Chronotherapeutic interventions regularising DRs, such as SRT, should be studied further as potential treatment strategies for BDAYA.Trial registration number NCT03183388.https://mentalhealth.bmj.com/content/28/1/e301338.full
spellingShingle Jihoon A Kim
Anjali Sankar
Rebecca Marks
Erin Carrubba
Bernadette Lecza
Susan Quatrano
Linda Spencer
R. Todd Constable
Brian Pittman
Eli R Lebowitz
Wendy K Silverman
Holly A Swartz
Hilary P Blumberg
Chronotherapeutic intervention targeting emotion regulation brain circuitry, symptoms, and suicide risk in adolescents and young adults with bipolar disorder: a pilot randomised trial
BMJ Mental Health
title Chronotherapeutic intervention targeting emotion regulation brain circuitry, symptoms, and suicide risk in adolescents and young adults with bipolar disorder: a pilot randomised trial
title_full Chronotherapeutic intervention targeting emotion regulation brain circuitry, symptoms, and suicide risk in adolescents and young adults with bipolar disorder: a pilot randomised trial
title_fullStr Chronotherapeutic intervention targeting emotion regulation brain circuitry, symptoms, and suicide risk in adolescents and young adults with bipolar disorder: a pilot randomised trial
title_full_unstemmed Chronotherapeutic intervention targeting emotion regulation brain circuitry, symptoms, and suicide risk in adolescents and young adults with bipolar disorder: a pilot randomised trial
title_short Chronotherapeutic intervention targeting emotion regulation brain circuitry, symptoms, and suicide risk in adolescents and young adults with bipolar disorder: a pilot randomised trial
title_sort chronotherapeutic intervention targeting emotion regulation brain circuitry symptoms and suicide risk in adolescents and young adults with bipolar disorder a pilot randomised trial
url https://mentalhealth.bmj.com/content/28/1/e301338.full
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