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

Abstract

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 (BD_AYA): 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 BD_AYA (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 (p _{FWE (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 BD_AYA.

Clinical implications: Chronotherapeutic interventions regularising DRs, such as SRT, should be studied further as potential treatment strategies for BD_AYA.

Trial registration number: NCT03183388.

Keywords: Child & adolescent psychiatry; Depression & mood disorders; PSYCHIATRY; Sleep; Suicide & self-harm.

Figure 1. Participant flow diagram. BE-SMART, Brain Emotion Circuitry-targeted Self-Monitoring and Regulation Therapy; DR, daily rhythm; ER, emotion regulation.

Figure 2. Decreases in left amygdala responses to face stimuli associated with improvements in daily rhythm regularity with Brain Emotion Circuitry Targeted Self-Monitoring and Regulation Therapy for Daily Rhythm (BE-SMART-DR). Coronal images display the left amygdala regions where decreases in brain oxygen level-dependent (BOLD) signal correlated significantly with improvements in Brief Social Rhythm Scale (BSRS) scores from before to after BE-SMART-DR. BSRS scores improved significantly from before to after BE-SMART-DR (p<0.05) and these changes were significantly associated with decreases in BOLD signal in the left amygdala when participants viewed faces depicting fearful (left image, p_FWE-SVC<0.05) and emotionally ambiguous (right image, p_FWE-SVC<0.05) expressions. The decreases in BOLD signal in the left amygdala to both face types also correlated significantly with reductions in scores on the Difficulties in Emotion Regulation Scale (DERS) and scores on the Concise Health Risk Tracking (CHRT) that reflect reductions in suicide risk. The colour bar represents the range of t-values. p_FWE-SVC, p-value corrected using family-wise error (FWE) correction with small volume correction (SVC).