INTRODUCTION
manic, anxiety, mood disorders, Bipolar disorder, mood instability, hyperactivity, mania, depressive, hypo/mania, hypomania, depressive symptoms, bipolar
RECURRENCES, REMISSION
Bipolar disorder (BD) can be recognized in childhood and adolescence, typically in the form of depressive symptoms or episodes, subsyndromal mania or hypomania, anxiety, and mood instability [The developmental pathways to the onset of BD in vulnerable youth are being clarified in genetic, neuroimaging, and psychosocial studies. Certain genes appear to mediate the relation between having a parent with BD and an offspring’s likelihood of developing BD [Despite these advances, it is unclear what parents or treating clinicians should do when behavioral or familial risk factors suggest a trajectory toward illness onset in a child or teen with early symptoms. Intervening with pharmacotherapy may lead to reductions in subthreshold symptoms in high-risk youth [These challenges have inspired the nascent work on preventative psychosocial interventions for youth at risk for BD. Preventative psychosocial interventions must have efficacy in minimizing early-onset symptoms as well as preventing future episodes, either alone or in combination with pharmacotherapy. Ideally, they should have an impact on the child’s reaction to stressors that may aggravate symptoms. In prior randomized trials, we have shown that a psychoeducational intervention called family-focused therapy (FFT), when combined with adequate pharmacotherapy, is effective in delaying recurrences and reducing symptom severity in adults with BD I and II [We reasoned that FFT could be adapted as an early intervention for youth at high risk for conversion to BD. FFT for high-risk youth (FFT-HR) begins when a youth with a family history of BD shows subthreshold manic or sub- or full threshold depressive symptoms. In 12 sessions over 4 months, clinicians provide the child and family members with psychoeducation about the nature, causes and prevention of mood disorders, followed by communication and problem-solving skills training to decrease family conflict and increase cohesion. In a pilot randomized trial of FFT-HR in 40 high-risk children, family treatment plus pharmacotherapy was more effective than brief education plus pharmacotherapy in decreasing time to recovery from mood episodes, increasing time in symptom remission, and reducing hypo/mania symptoms over one year [This article describes clinical outcomes from a larger-scale randomized trial of high-risk youth recruited from three study sites. We compared FFT-HR with a duration-matched, standardized psychoeducational therapy (enhanced usual care, or EC) on symptomatic outcomes (To comprehensively investigate the engagement of progressively higher-order neural systems targeted by early intervention, we used three methods of assaying changes in corticolimbic circuits from before to after FFT-HR or EC: in the resting state, during a facial emotion processing task, and during a problem-solving task. We hypothesized that key intrinsic connectivity patterns associated with known bipolar networks, as shown in the resting state, would change with treatment, as would amygdala activation during face emotion processing. Further, because amygdala hyperactivity and diminished prefrontal inhibitory control have been associated with mood instability in BD [