Computational Mechanisms of Approach-Avoidance Conflict Predictively Differentiate Between Affective and Substance Use Disorders

Psychiatric disorders are highly heterogeneous and often co-morbid, posing specific challenges for effective treatment. Recently, computational modeling has emerged as a promising approach for characterizing sources of this heterogeneity, which could potentially aid in clinical differentiation. In this study, we tested whether computational mechanisms of decision-making under approach-avoidance conflict (AAC) - where behavior is expected to have both positive and negative outcomes - may have utility in this regard. We first carried out a set of pre-registered modeling analyses in a sample of 480 individuals who completed an established AAC task. These analyses aimed to replicate cross-sectional and longitudinal results from a prior dataset (N = 478) - suggesting that mechanisms of decision uncertainty (<i>DU</i>) and emotion conflict (<i>EC</i>) differentiate individuals with depression, anxiety, substance use disorders, and healthy comparisons. We then combined the prior and current datasets and employed a stacked machine learning approach to assess whether these computational measures could successfully perform out-of-sample classification between diagnostic groups. This revealed above-chance differentiation between affective and substance use disorders (balanced accuracy > 0.688), both in the presence and absence of co-morbidities. These results demonstrate the predictive utility of computational measures in characterizing distinct mechanisms of psychopathology and may point to novel treatment targets.