Changes in Intrinsic Brain Connectivity in Family-Focused Therapy Versus Standard Psychoeducation Among Youths at High Risk for Bipolar Disorder

Abstract

We compared intrinsic network connectivity in symptomatic youths at high risk (HR) for bipolar disorder (BD) and healthy comparison (HC) youths. In HR youths, we also investigated treatment-related changes in intrinsic connectivity after family-focused therapy for high-risk youths (FFT-HR) vs standardized family psychoeducation. HR youths (N= 34; age 9-17 years; mean 14 years, 56% girls and 44% boys) with depressive and/or hypomanic symptoms and at least 1 first- or second-degree relative with BD I or II were randomly assigned to 4 months of FFT-HR (12 sessions of psychoeducation, communication, and problem-solving skills training) or enhanced care (EC; 3 family and 3 individual psychoeducation sessions). Before and after 4 months of treatment, participants underwent resting state functional magnetic resonance imaging (rs-fMRI). A whole-brain independent component analysis compared rs-fMRI networks in HR youths and 30 age-matched HC youths at a pretreatment baseline. Then we identified pretreatment to posttreatment (4-month) changes in network connectivity in HR youths receiving FFT-HR (n= 16) or EC (n= 18) and correlated these changes with depression improvement. At baseline, HR youths had greater connectivity between the ventrolateral prefrontal cortex (VLPFC) and the anterior default mode network (aDMN) than did HCs (p= .004). Over 4 months of treatment, FFT-HR-assigned HR youths had increased VLPFC-aDMN connectivity from pre- to posttreatment (p= .003), whereas HR youths in EC showed no significant change over time (p= .11) (treatment by time interaction, t31= 3.33, 95% CI= 0.27-1.14, p= .002]. Reduction in depression severity over 4 months inversely correlated with enhanced anterior DMN (r=-0.71) connectivity in the FFT-HR but not in the EC (r=-0.07) group (z=-2.17, p= .015). Compared to standard psychoeducation, FFT-HR is associated with stronger connectivity between the VLPFC and aDMN, suggesting possible enhancements of self-awareness, illness awareness, and emotion regulation. Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.