did not change after ketamine, antidepressant treatment, or internet-delivered CBT in depression.
Evidence
Across two longitudinal treatment studies using a two-step reinforcement learning task, 93 patients with were randomized to IV ketamine or saline and 781 participants were followed for 4 weeks of antidepressants or iCBT, with symptom improvement but no evidence of change in model-based planning.
Caveat
The null finding comes from specific short-term interventions and follow-up windows, so it does not rule out other cognitive deficits in depression or changes under different treatment conditions.
Simplified
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 (''). Nevertheless, results of model-based planning in depression have 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. 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 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. In both experiments, depressive symptoms significantly improved in treatment groups compared to their corresponding control groups, but we did not find evidence of changes in model-based planning. Moreover, we failed to find associations between individual differences in model-based planning and differential response to ketamine, iCBT or antidepressant treatments. Individual differences in model-based planning at baseline were associated with compulsivity, but not with depression symptoms. 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.
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Competing interests: KRD, SH, KL, CF, AKH, VOK, KES, BMP and CMG have no conflicts of interest to declare. CTL and SiH are current employees of SilverCloud Health. VMB has received consulting fees from Aya Technologies. KES acknowledges core funding by the Rene and Susanne Braginsky Foundation and the ETH Foundation. RBP is the named inventor on a University of Pittsburgh–owned patent filing related to the combination intervention that was used in the parent clinical trial.
