Family history of depression is associated with alterations in task-dependent connectivity between the cerebellum and ventromedial prefrontal cortex

Background A family history of major depressive disorder (MDD) increases the likelihood of a future depressive episode, which itself poses a significant risk for disruptions in reward processing and social cognition. However, it is unclear whether a family history of MDD is associated with alterations in the neural circuitry underlying reward processing and social cognition. Methods We subdivided 279 participants from the Human Connectome Project into three groups: 71 with a lifetime history of MDD, 103 with a family history (FH) of MDD, and 105 healthy controls (HCs). We then evaluated task-based functional magnetic resonance imaging data on a social cognition and a reward processing task and found a region of the ventromedial prefrontal cortex (vmPFC) that responded to both tasks, independent of the group. To investigate whether the vmPFC shows alterations in functional connectivity between groups, we conducted psychophysiological interaction analyses using the vmPFC as a seed region. Results We found that FH (relative to HC) was associated with increased sadness scores, and MDD (relative to both FH and HC) was associated with increased sadness and MDD symptoms. Additionally, the FH group had increased vmPFC functional connectivity within the nucleus accumbens, left dorsolateral PFC, and subregions of the cerebellum relative to HC during the social cognition task. Conclusions These findings suggest that aberrant neural mechanisms among those with a familial risk of MDD may underlie vulnerability to altered social cognition.