THE ENDOPHENOTYPE OF EMOTIONAL REGULATION IN OBSESSIVE-COMPULSIVE DISORDER (OCD)

Abstract

Introduction OCD symptoms have been associated with task-dependent alterations in brain activity implying dysregulation in limbic (e.g. the amygdala) and frontal-striatal circuits. Emerging evidence shows that there are functional neural endophenotypes in executive processing suggesting compensatory hyperactivation of fronto-parietal executive control networks and fronto-limbic dysregulation in OCD patients and first-degree relatives (de Wit et al., 2012; van Velzen et al., 2015). There are however few studies on emotional processing using a family-study design. We recently showed altered frontal-parietal and limbic functioning in OCD patients during emotion processing and emotion regulation (de Wit et al., 2015), but it remains unclear if these changes are also present in first-degree relatives. Method Forty-three unmedicated adult OCD patients, 19 of their unaffected siblings and 38 healthy controls underwent functional magnetic resonance imaging (MRI) during an emotion regulation task including neutral, fear and OCD-related visual stimuli. Stimuli were processed during natural appraisal (‘attend’ instruction) and during cognitive reappraisal (‘regulate’ instruction). Self-report distress ratings were collected from each picture. The neural correlates of emotion regulation were assessed using SPM12. Results Fear and OCD symptom provocation resulted in higher self-report distress ratings in patients compared with both siblings and healthy controls. Functional MRI analyses showed that specifically during OCD-related provocation, compared with controls, BOLD activation amplitude and timing was altered in the left hippocampus, right caudate nucleus and amygdala (for both patients and siblings), and bilateral thalamus (for siblings only). During fear regulation we previously found fronto-parietal hypoactivation in OCD patients, but fronto-parietal activation was not significantly different in siblings from patients or controls. During regulation of OCD-related stimuli siblings were more similar to patients (i.e. showing hyperactivation of the dorsomedial PFC (dmPFC) compared with controls). Compared with both patients and controls, hyperactivation in siblings was more extensive (including the supplementary motor area and parietal regions), and siblings showed increased dmPFC-connectivity with the middle cingulate, superior temporal, and superior frontal cortices during OCD-related emotion regulation. The diminished dmPFC-amygdala connectivity we previously reported in OCD patients during fear-regulation was not present in the sibling group. Discussion Unaffected siblings of OCD patients were similar to controls on the behavioral response to emotional provocation, but showed dissimilar neural responses during OCD-related emotion provocation and regulation compared to healthy controls, while there were fewer differences for general fear stimuli. During OCD-related emotion provocation we observed altered activation in limbic and striatal regions in both OCD patients and siblings. During OCD-related emotion regulation siblings showed few differences compared to patients, but showed increased activation in fronto-parietal and temporal areas compared to controls. Siblings also showed extensive dmPFC hyperconnectivity compared to the patients and controls, which suggests a compensatory response. These results extend previous findings of functional endophenotypes in OCD, and show dissociation between subjective distress and brain activity during emotion processing in unaffected siblings of people with OCD.