DISCUSSION
ideation, ideation/behavior, mood instability, rigidity, depressive, hypo/mania, depressive symptoms, depression, Depression
CORTEX
In this article, we have presented clinical, psychosocial, and neuroimaging results from one of the first randomized trials of a psychosocial intervention in the early stages of BD. Following phenomenological research on offspring of parents with BD [Our results suggest that in high-risk youth, a brief family psychoeducational therapy is effective in reducing the likelihood of new depressive episodes and suicidal ideation or behaviors over an average of 2 years after a period of mood symptoms. We identified possible psychosocial and neural mediating mechanisms of these treatment effects. First, the youth’s view of family functioning, such as whether the mother/child relationship is characterized by high or low conflict, is an important mediator of whether children show improvements in depressive symptoms or suicidal ideation/behavior in FFT-HR compared to EC. Whether it is critical to work directly with the family to achieve these changes in youth’s perceptions or whether such changes can emerge from individual cognitive restructuring or acceptance-based interventions deserves investigation.The neuroimaging results have implications for understanding brain mechanisms in high-risk youth at rest while processing emotions and while attempting to regulate emotions during problem-solving, as well as the ways in which these functions change with psychosocial intervention. Resting-state findings indicate that compared to EC, FFT-HR was associated with stronger connectivity between the VLPFC and aDMN, possibly indicating enhanced self-awareness, illness awareness, and emotion regulation. Stronger connectivity was associated with improvements in mood lability on the parent-rated CALS. FFT-HR was also associated with increased anterior DMN connectivity, which was correlated with pre- to post-treatment improvements in Children’s Depression Rating Scale scores. DMN connectivity, in concert with enhanced prefrontal connectivity, may reflect adaptive changes in neural networks indicative of “neural reserve” or the capacity to tolerate brain insults [Changes in neural networks in youth at risk for BD are observable at rest prior to symptom onset, as demonstrated by previous findings that VLPFC-caudate dysconnectivity correlates with family chaos and amygdala-fusiform dysconnectivity correlates with family rigidity in healthy offspring of parents with BD, compared to offspring of healthy parents or offspring of parents with depression [We observed that during the emotion processing task, DLPFC activation increased from pre- to post-treatment in the FFT-HR group but not in the EC group. These increases were also correlated with improvement in depressive symptoms, while pre/post decreases in amygdala/hippocampal activation were correlated with improvement in hypo/mania symptoms. In the family situations problem-solving task, activation in the medial frontal cortex increased from pre- to post-treatment in the FFT-HR group more than in the EC group, and was correlated with improvements in mood instability. Thus, across tasks, psychosocial treatment was associated with the enhancement of emotion regulation circuitry, although the specific location within the frontal cortex differed based on task design and demands.Our findings indicate changes during treatment in corticolimbic networks that promote emotion regulation, self-reflection, and awareness. These changes correlate with improvements in symptoms and behavior, and they occur to a greater extent in FFT-HR than in standard psychoeducation. Together, these neuroimaging findings across rest and task-based fMRI suggest that the change mechanisms of FFT-HR and EC may be separable, with FFT-HR having a greater association with executive regulatory control through the prefrontal cortex, commensurate with the teaching of communication and problem-solving skills in FFT-HR that promote these functions.