Diminished error-related brain activity as a promising endophenotype for substance-use disorders: evidence from high-risk offspring

One of the core features of individuals with a substance-use disorder (SUD) is the reduced ability to successfully process errors and monitor performance, as reflected by diminished error-related negativities (ERN). However, whether these error-related brain abnormalities are caused by chronic substance use or rather predates it remains unclear. The present study elucidated whether hypoactive performance monitoring represents an endophenotypic vulnerability marker for SUD by using a high-risk paradigm. We assessed the behavioral components of error-processing, as well as the amplitude of the ERN in the event-related brain potential (ERP) during performance of the Eriksen Flanker Task among high-risk adolescents of parents with a SUD (HR; n=28) and normal-risk controls (NR; n=40). Results revealed that HR offspring were characterized by a higher prevalence of internalizing symptoms and more frequent cannabis use, the latter having a significant influence on the ERN. Interestingly, risk group uniquely predicted the negativity amplitude in response to error trials above and beyond confounding variables. Moreover, we found evidence of smaller ERN amplitudes in (cannabis use-naive) HR offspring, reflecting impaired early processing of error information and suboptimal performance monitoring, whereas no robust group differences were found for overall behavioral performance. This effect was independent of an overall reduction in brain activity. Taken together, although we cannot rule out alternative explanations, the results of our study may provide evidence for the idea that diminished error-processing represents a promising endophenotype for SUD that may indicate a vulnerability to the disorder.