The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD's heritability are still unknown, findings from genome-wide association studies (GWAS) corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by a polygenic risk score (PRS), and potential endophenotypes of the disorder, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. METHODS: We derived PRS for OCD at several P-value thresholds based on the latest Psychiatric Genomics Consortium OCD GWAS (2688 cases, 7037 controls) in an independent sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). Using linear regression, we tested whether these PRS are associated with the personality trait harm avoidance. RESULTS: Results showed that OCD PRS significantly predicted OCD status, with patients having the highest scores and relatives having intermediate scores. Furthermore, the genetic risk for OCD was associated with harm avoidance across the entire sample, and among OCD patients. As indicated by mediation analyses, harm avoidance mediated the association between the OCD PRS and OCD caseness. These results were observed at multiple P-value thresholds and persisted after the exclusion of patients with a current comorbid major depressive or anxiety disorder. CONCLUSION: Our findings support the polygenic nature of OCD and further validate harm avoidance as a candidate endophenotype and diathesis of OCD.

Harm avoidance and childhood adversities in patients with obsessive-compulsive disorder and their unaffected first-degree relatives.

OBJECTIVE: The etiology of obsessive-compulsive disorder (OCD) is assumed to involve interactions between genetically determined vulnerability factors and significant environmental features. Here, we aim to investigate how the personality trait harm avoidance and the experience of childhood adversities contribute to OCD. METHOD: A total of 169 patients with OCD, 157 healthy comparison subjects, and 57 unaffected first-degree relatives of patients with OCD participated in the study. Harm avoidance was assessed using the Temperament and Character Inventory, and the severity of childhood adversities was measured with the Childhood Trauma Questionnaire. RESULTS: Both patients with OCD and relatives showed elevated levels of harm avoidance compared to controls. Furthermore, patients exhibited significantly higher scores than relatives. This linear pattern was observed throughout all subscales of harm avoidance, and remained stable after controlling for the severity of depressive and obsessive-compulsive symptoms. With regard to childhood adversities, patients with OCD reported higher levels than relatives and controls. CONCLUSION: Our results provide further evidence for a diathesis-stress model of OCD. While patients and unaffected relatives share elevated levels of harm avoidance, supporting the role of harm avoidance as an endophenotype of OCD, a heightened severity of childhood adversity was only observed in patients. The assumed biological underpinnings of these findings are discussed.

Conflict monitoring and adaptation as reflected by N2 amplitude in obsessive-compulsive disorder.

BACKGROUND: Feelings of doubt and perseverative behaviours are key symptoms of obsessive-compulsive disorder (OCD) and have been linked to hyperactive error and conflict signals in the brain. While enhanced neural correlates of error monitoring have been robustly shown, far less is known about conflict processing and adaptation in OCD. METHOD: We examined event-related potentials during conflict processing in 70 patients with OCD and 70 matched healthy comparison participants, focusing on the stimulus-locked N2 elicited in a flanker task. Conflict adaptation was evaluated by analysing sequential adjustments in N2 and behaviour, i.e. current conflict effects as a function of preceding conflict. RESULTS: Patients with OCD showed enhanced N2 amplitudes compared with healthy controls. Further, patients showed stronger conflict adaptation effects on reaction times and N2 amplitude. Thus, the effect of previous compatibility was larger in patients than in healthy participants as indicated by greater N2 adjustments in change trials (i.e. iC, cI). As a result of stronger conflict adaptation in patients, N2 amplitudes were comparable between groups in incompatible trials following incompatible trials. CONCLUSIONS: Larger N2 amplitudes and greater conflict adaptation in OCD point to enhanced conflict monitoring leading to increased recruitment of cognitive control in patients. This was most pronounced in change trials and was associated with stronger conflict adjustment in N2 and behaviour. Thus, hyperactive conflict monitoring in OCD may be beneficial in situations that require a high amount of control to resolve conflict, but may also reflect an effortful process that is linked to distress and symptoms of OCD.