Early intervention for youth at high risk for bipolar disorder: A multisite randomized trial of family-focused treatment

Aims: Despite the considerable public health impact of bipolar disorder (BD), no psychosocial interventions have been systematically evaluated in its early prodromal stages. We describe the rationale, design and analytic methods for a 3-site randomized trial of family-focused treatment for youth at high risk (FFT-HR) for BD. Methods: Participants (ages 9-17 years) have a diagnosis of unspecified BD or major depressive disorder, current mood symptoms and at least one first- or second-degree relative with a lifetime history of BD I or II. Participants are randomly assigned to FFT-HR (12 sessions in 4 months of family psychoeducation and skills training) or enhanced care (EC; 6 individual and family sessions over 4 months), with pharmacotherapy provided as needed. A subset of participants undergo pre- and post-treatment functional MRI (fMRI) scans while performing face-rating and family problem-solving tasks designed to activate corticolimbic circuitry. Independent evaluators assess participants’ status every 4 to 6 months for up to 4 years. Results: We hypothesize that FFT-HR will be more effective than EC in reducing the severity of mood symptoms (primary outcome) and the hazard of a first manic episode (secondary) over 4 years. Secondarily, we will explore whether FFT-HR is associated with greater decreases in amygdala activation and increases in dorsolateral, ventrolateral or anterior medial prefrontal cortex activation from pre- to post-treatment. Clinical characteristics of 133 subjects enrolled at baseline are described. Conclusions: This study will test a novel intervention to reduce the early symptoms of BD, and identify neural and behavioural mechanisms that may help refine future treatments.