Ketamine and belief updating: Neurocognitive mechanisms in the treatment of major depressive disorder. – KETABELIEF

Major depressive disorder is a debilitating disease. Despite its significance, the neurocognitive mechanisms involved in clinical remission remain mysterious. One out of three patients does not respond to monoaminergic treatments, leading to the diagnosis of treatment-resistant depression (TRD). Here we aim to identify and specify the mechanisms of a novel, fast-acting antidepressant treatment strategy consisting of subanesthetic ketamine infusions in TRD patients. We will combine behavioral testing of biases in belief updating and emotion processing with a pharmacological challenge comparing early and tardive effects of ketamine to monoaminergic antidepressants. Functional magnetic resonance imaging and computational modeling will provide further insights into the neurocomputational mechanisms of ketamine action. Findings will provide first-time insights into how ketamine improves clinical symptoms, and offer new perspectives for the treatment of mood disorders.