Computational Psychiatry & Decision-making

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  • Computational mechanisms of effort and reward decisions in depression and their relationship to relapse after antidepressant discontinuation
  • Berwian IM, Wenzel J, Collins AGE, Seifritz E, Stephan KE, Walter H, Huys QJM
  • JAMA Psychiatry (2020)
  • Importance: Nearly one in three patients with Major Depressive Disorder (MDD) who respond to antidepressants re- lapse within six months of treatment discontinuation. No predictors to guide clinical decision-making exist. Objective: Establish whether the decision to invest effort for rewards 1) represents a persistent depression process after remission, 2) predicts relapse after and 3) is affected by antidepressant discontinuation. Design: Longitudinal randomised observational study Setting: Swiss and German university setting. Data collection from July 2015 to January 2019. Participants: Patients remitted from MDD in response to antidepressants prior to discontinuation and matched healthy controls. Exposure: Discontinuation of antidepressants. Main Outcome: Relapse over 6 months after discontinuation. Main measures: Choice and decision times on a task requiring participants to choose how much effort to exert for various amounts of reward and mechanisms identified through parameters of a computational model. Results: 123 patients (age 34.5(11.2)), 76% women) and 66 healthy controls (age 34.6(11.0), 74% women) were re- cruited. In the main subsample, decision times were slowed in patients (p=0.015; patients: n=74, 1.77s(0.38), controls: n=34, 1.61s(0.37), d'=0.52), particularly in those who later relapsed after discontinuation (p<0.001, relapsers: n=21, 1.95s(0.40), non-relapsers: n=39, 1.67s(0.34), d'=0.77) and this predicted relapse (accuracy=0.66, p=0.007). Patients invested less effort for rewards than healthy controls (p<.001). Computational modelling identified a deviation from stan- dard drift-diffusion models that was more prominent in patients than controls (p<0.001, patients: 0.67(1.56), controls: -0.71(1.93), d'=0.82). Patients also showed higher effort sensitivity (p=0.05, patients: 0.31(0.92), controls: -0.08(0.21), d'=0.51). Relapsers differed from non-relapsers in terms of the evidence required to make a decision for the low effort choice (p=0.021, relapsers: 1.36(0.35), non-relapsers: 1.17(0.26), d'=-0.65). Group differences generally did not reach significance in the smaller replication sample (27 patients, 21 controls), but decision time prediction models from the main sample generalised to the replication sample (validation accuracy=0.71, p=0.03). Conclusion and Relevance: The decision to invest effort indexes prospective relapse risk after antidepressant discon- tinuation, and may represent a persistent disease process in asymptomatic remitted MDD. Markers based on effort- related decision making could potentially inform clinical decisions relating to antidepressant discontinuation.