Negative learning bias in depression revisited: Enhanced neural response to surprising reward across psychiatric disorders

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Background: Prior work has proposed that major depressive disorder (MDD) is associated with a specific cognitive bias: Depressed patients seem to learn more from punishment than reward. This learning bias has been associated with blunting of reward-related neural responses in the striatum. A key question is whether negative learning bias is also present in MDD patients with comorbid disorders, and whether this bias is specific to depression, or shared across disorders. Methods: We employed a transdiagnostic approach, assessing a heterogenous group of (non-psychotic) psychiatric patients from the MIND-Set cohort (Radboudumc, the Netherlands), with and without MDD but also suffering from anxiety, ADHD and/or autism (n=66) and healthy controls (n=24). To investigate reward and punishment learning, we employed a deterministic reversal learning task with functional MRI. Results: In contrast to previous studies, MDD patients did not exhibit impaired reward learning or reduced reward-related neural activity anywhere in the brain. Interestingly, we observed consistently increased neural responses in bilateral lateral prefrontal cortex of patients when they received a surprising reward. This increase was not specific to MDD, but generalized to anxiety, ADHD and autism. Critically, increased prefrontal activity to surprising reward scaled with transdiagnostic symptom severity, particularly those associated with concentration and attention, as well as the number of diagnoses; patients with more comorbidities showed a stronger prefrontal response to surprising reward. Conclusions: Prefrontal enhancement may reflect compensatory working-memory recruitment, possibly to counteract the inability to swiftly update reward expectations. This neural mechanism may provide a candidate transdiagnostic index of psychiatric severity.