Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects.

The international journal of neuropsychopharmacology  – February 04, 2025

Source: PubMed

Summary

Ketamine's remarkable ability to lift severe depression within hours has revolutionized our understanding of mental health treatment. New research reveals this breakthrough antidepressant works by simultaneously targeting multiple brain systems - enhancing reward processing, improving body awareness, and shifting self-perception. This neurocognitive approach explains how ketamine helps break the cycle of negative thinking and emotional numbness common in depression.

Abstract

Ketamine is an N-methyl-D-aspartate receptor antagonist that has shown effectiveness as a rapidly acting treatment for depression. Although advances have been made in understanding ketamine's antidepressant pharmacological and molecular mechanisms of action, the large-scale neurocognitive mechanisms driving its therapeutic effects are less clearly understood. To help provide such a framework, we provide a synthesis of current evidence linking ketamine treatment to the modulation of brain systems supporting reward processing, interoception, and self-related cognition. We suggest that ketamine's antidepressant effects are, at least in part, driven by dynamic multi-level influences across these key functional domains.

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