Model-based planning is unaffected by ketamine, antidepressant and internet delivered cognitive behavioural therapy treatments

Background: Cognitive impairments have been observed in patients with depression. These include deficits in inhibition, shifting, and updating; cognitive processes that are critical for goal-directed control over behavior (‘model-based planning’). But despite this, research investigating model-based planning in depression has itself been mixed. We aimed to address this by taking a within-person approach, examining model-based planning before and after a range of effective treatments for depression. Method: Across two parallel studies, participants completed a two-step reinforcement learning paradigm before and after antidepressant medication, internet-based cognitive behavioral therapy (iCBT) or intravenous (IV) ketamine infusion. In experiment 1, 93 patients with treatment-resistant depression were randomized to a single dose of IV ketamine (0.5 mg/kg) or IV saline (50 mL 0.9% NaCl). In Experiment 2, 781 participants were followed for four weeks of antidepressant (N=83), or iCBT (N=611) treatment. N=87 participants without any psychiatric diagnosis were followed as a control group. Results: In both experiments, depressive symptoms significantly improved in treatment groups compared to their corresponding control groups, but model-based planning did not change. Moreover, individual differences in model-based planning did not predict differential response to ketamine, iCBT or antidepressant treatments. Individual differences in model- based planning at baseline were associated with compulsivity, but not depression symptoms. Conclusions: These findings suggest that model-based planning is not necessarily compromised in depression and does not improve following treatments. This result provides evidence for the trait-like nature of model-based planning and underscores the specificity of its relation to disorders of compulsivity.