Abstract
BACKGROUND: Aberrant neural and cognitive response to emotional faces has been observed in people at familial risk of an affective disorder. In this functional MRI study of monozygotic twins, we explored neural correlates of the attentional avoidance of emotional faces that we had previously observed in high-risk versus affected twins, and whether an abnormal neural response to emotional faces represents a risk endophenotype. METHODS: We recruited unaffected monozygotic twins with a co-twin history of mood episodes (high-risk), monozygotic twins with previous mood episodes (affected) and monozygotic twins with no personal or first-degree history of mood episodes (low-risk) between December 2014 and January 2017 based on a nationwide register linkage. Participants viewed fearful and happy faces while performing a gender discrimination task during functional MRI (fMRI) and performed emotional faces dot-probe and facial expression recognition tasks outside the scanner. RESULTS: A total of 129 monozygotic twins underwent whole-brain fMRI. Highrisk twins (n = 38) displayed greater medial and superior prefrontal response to emotional faces than affected twins (n = 62). This greater activity correlated with stronger attentional avoidance of emotional faces in high-risk twins. In contrast, high-risk and affected twins showed no aberrant neural activity to emotional faces compared with low-risk twins (n = 29). LIMITATIONS: A limitation of this study was its cross-sectional design. CONCLUSION: Greater recruitment of the medial and superior prefrontal cortex during implicit emotion processing in high-risk versus affected twins may represent a compensatory or resilience mechanism. In contrast, aberrant neural response to emotional faces does not seem to be a risk endophenotype for affective disorders.