The erring brain: Error-related negativity as an endophenotype for OCD-A review and meta-analysis

Obsessive-compulsive disorder (OCD) is a complex and heterogeneous disorder that is associated with high personal and societal costs. Feelings of doubt, worry, and repetitive behavior, key symptoms of OCD, have been linked to hyperactive error signals in the brain. The error-related negativity (ERN) represents a validated marker of error processing in the ERP. Increased ERN amplitudes in OCD have been reported very robustly over the last 20 years. This article integrates results from 38 studies analyzing the ERN in OCD, using a quantitative meta-analysis. Meta-regressions were used to examine potential moderators such as task type, symptom severity, age, and sample size. The meta-analysis reveals a robust increase of ERN in OCD patients compared to healthy participants in response-conflict tasks (SMD -0.55) that is not modulated by symptom severity and age. No increase in ERN in OCD was observed in tasks that do not induce response conflict (SMD -0.10). In addition to the meta-analysis, the current article reviews evidence supporting that increased ERN amplitudes in OCD fulfill central criteria for an endophenotype. Further, the specificity of increased ERN amplitudes for OCD and its suitability as a potential transdiagnostic endophenotype is discussed. Finally, the clinical utility and clinical applications are examined. Overall, the evidence that increased ERN amplitudes represent a promising endophenotype indicating vulnerability for OCD is compelling. Furthermore, alterations in ERN are not limited to OCD and may constitute a transdiagnostic endophenotype. Altered neural error signals might serve as a diagnostic or predictive marker and represent a promising target for interventions.