Neural Correlates of Positive Emotion Processing That Distinguish Healthy Youths at Familial Risk for Bipolar Versus Major Depressive Disorder

Abstract

Familial risk for bipolar disorder (BD) or major depressive disorder (MDD) may lead to differential emotion processing signatures, resulting in unique neural vulnerability. Healthy offspring of a parent with BD (n= 29, "BD-risk") or MDD (n= 44, "MDD-risk") and healthy control youths without any personal or family psychopathology (n= 28, "HC") aged 8 to 17 years (13.64 ± 2.59 years) completed an implicit emotion-perception functional magnetic resonance imaging task. Whole-brain voxelwise and psychophysiological interaction analyses examined neural differences in activation and connectivity during emotion processing. Regression modeling tested for neural associations with behavioral strengths and difficulties and conversion to psychopathology at follow-up (3.71 ± 1.91 years). BD-risk youth showed significantly reduced bilateral putamen activation, and decreased connectivity between the left putamen and the left ventral anterior cingulate cortex (vACC) and the right posterior cingulate cortex (PCC) during positive-valence emotion processing compared to MDD-risk and HC (Z >2.3; p<.001). Decreased left putamen-right PCC connectivity correlated with subsequent peer problems in BD-risk (β=-2.90; p<.05) and MDD-risk (β=-3.64; p< .05) groups. Decreased left (β=-0.09; p< .05) and right putamen activation (β=-0.07; p= .04) were associated with conversion to a mood or anxiety disorder in BD-risk youths. Decreased left putamen-right PCC connectivity was associated with a higher risk of conversion in BD-risk (HR= 8.28 , p< .01) and MDD-risk (HR= 2.31, p= .02) groups. Reduced putamen activation and connectivity during positive emotion processing appear to distinguish BD-risk youths from MDD-risk and HC youths, and may represent a marker of vulnerability.