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

Objective: 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. Method: 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. Results: 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). Conclusion: 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. Clinical trial registration information: Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.