TY - JOUR T1 - Associations between aversive learning processes and transdiagnostic psychiatric symptoms revealed by large-scale phenotyping JF - bioRxiv DO - 10.1101/843045 SP - 843045 AU - Toby Wise AU - Raymond J Dolan Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/15/843045.abstract N2 - Background Aversive learning processes are a candidate source of dysfunction in psychiatric disorders. Here symptom expression in a range of conditions is linked to altered threat perception, manifesting particularly in uncertain environments. How precise computational mechanisms that support aversive learning, and uncertainty estimation, relate to the presence of specific psychiatric symptoms remains undetermined.Methods 400 subjects completed a novel online game-based aversive learning task, requiring avoidance of negative outcomes, in conjunction with completing measures of common psychiatric symptoms. We used a probabilistic computational model to measure distinct processes involved in learning, in addition to inferred estimates of safety likelihood and uncertainty. We tested for associations between learning processes and traditional psychiatric constructs alongside transdiagnostic factors using linear models. We used partial least squares regression to identify components of psychopathology grounded in both aversive learning behaviour and symptom self-report.Results State anxiety and a transdiagnostic compulsivity-related factor were associated with enhanced learning from safety. However, data-driven analysis using partial least squares regression indicated the presence of two separable components across our behavioural and questionnaire data: one linked enhanced safety learning and lower estimated uncertainty to physiological anxiety, compulsivity, and impulsivity; the other linked enhanced threat learning and heightened uncertainty estimation to symptoms of depression and social anxiety.Conclusions Our findings implicate aversive learning processes under uncertainty to the expression of psychiatric symptoms that cut across traditional diagnostic boundaries. These relationships are more complex than previously conceptualised. Future research should focus on understanding the neural mechanisms underlying alterations in aversive learning and how these lead to the development of symptoms and disorder. ER -