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

J Am Acad Child Adolesc Psychiatry. 2021 Apr;60(4):458-469. doi: 10.1016/j.jaac.2020.07.892. Epub 2020 Aug 1.


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;; NCT01483391.

Keywords: bipolar disorder; depression; familial risk; family-focused therapy; resting state functional connectivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bipolar Disorder* / diagnostic imaging
  • Bipolar Disorder* / therapy
  • Brain / diagnostic imaging
  • Child
  • Family Therapy
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Reference Standards
  • Treatment Outcome

Associated data