Distinct alterations in probabilistic reversal learning across at-risk mental state, first episode psychosis and persistent schizophrenia

Sci Rep. 2024 Jul 30;14(1):17614. doi: 10.1038/s41598-024-68004-7.

Abstract

We used a probabilistic reversal learning task to examine prediction error-driven belief updating in three clinical groups with psychosis or psychosis-like symptoms. Study 1 compared people with at-risk mental state and first episode psychosis (FEP) to matched controls. Study 2 compared people diagnosed with treatment-resistant schizophrenia (TRS) to matched controls. The design replicated our previous work showing ketamine-related perturbations in how meta-level confidence maintained behavioural policy. We applied the same computational modelling analysis here, in order to compare the pharmacological model to three groups at different stages of psychosis. Accuracy was reduced in FEP, reflecting increased tendencies to shift strategy following probabilistic errors. The TRS group also showed a greater tendency to shift choice strategies though accuracy levels were not significantly reduced. Applying the previously-used computational modelling approach, we observed that only the TRS group showed altered confidence-based modulation of responding, previously observed under ketamine administration. Overall, our behavioural findings demonstrated resemblance between clinical groups (FEP and TRS) and ketamine in terms of a reduction in stabilisation of responding in a noisy environment. The computational analysis suggested that TRS, but not FEP, replicates ketamine effects but we consider the computational findings preliminary given limitations in performance of the model.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Female
  • Humans
  • Ketamine*
  • Male
  • Psychotic Disorders* / drug therapy
  • Psychotic Disorders* / physiopathology
  • Psychotic Disorders* / psychology
  • Reversal Learning* / physiology
  • Schizophrenia* / drug therapy
  • Schizophrenia* / physiopathology
  • Schizophrenic Psychology
  • Young Adult

Substances

  • Ketamine