Emotion Regulation in Obsessive-Compulsive Disorder, Unaffected Siblings, and Unrelated Healthy Control Participants

Abstract Objective Functional neuroimaging endophenotypes of obsessive-compulsive disorder (OCD) have been suggested during executive tasks. The purpose of this study was to investigate whether behavioral and neural responses during emotion processing and regulation also represent an endophenotype of OCD. Method Forty-three unmedicated adult OCD patients, 19 of their unaffected siblings and 38 healthy controls underwent 3T functional magnetic resonance imaging during an emotion regulation task including neutral, fear-inducing and OCD-related visual stimuli. Stimuli were processed during natural appraisal and during cognitive reappraisal, and distress ratings were collected after each picture. We performed between-group comparisons on task behavior and brain activation in regions-of-interest (ROI) during emotion provocation and regulation. Results Siblings reported similar distress as healthy controls during provocation, and significantly less than patients. There was no significant three-group difference in activation during fear provocation or regulation. Three-group comparisons showed that patients had higher amygdala and dorsomedial prefrontal cortex activation during OCD-related emotion provocation and regulation, respectively, while siblings were intermediate between patients and controls but not significantly different from either. Siblings showed higher left temporo-occipital activation (compared to both healthy controls and patients) and higher fronto-limbic connectivity (compared to patients) during OCD-related regulation. Conclusions Unaffected siblings do not show the same distress and amygdala activation during emotional provocation as OCD patients. Siblings show distinct activation in a temporo-occipital region, possibly related to compensatory cognitive control. This suggests that emotion regulation is not a strong endophenotype for OCD. When replicated, this contributes to our understanding of familial risk and resilience for OCD.