Ketamine-related neural changes in treatment-resistant depression: A multimodal synthesis of fMRI and PET studies.
Nesreen Sedeek, Carley Rivers, Lucas Williamson, Ayoub Asadi, John G Grundy
Journal of Affective Disorders April 28, 2026 DOI: 10.1016/j.jad.2026.121891 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review with multimodal synthesis Peer reviewed |
|---|---|
| Population | Adults with treatment-resistant depression |
| Intervention | Ketamine |
| Topics | Ketamine Depression Esketamine |
| Keywords | Brain networks Multimodal synthesis PET Treatment-resistant depression trd FMRI |
| Key findings | Ketamine-related effects were frequently reported in subcortical regions, with distributed and context-dependent effects across cortical systems, and network-level summaries suggested involvement of default-mode, ventral attention, and visual systems. |
Abstract
Ketamine produces rapid antidepressant effects in a subset of patients with treatment-resistant depression, yet neuroimaging findings have been difficult to integrate because studies differ in imaging modality, analytic approach, task context, and post-infusion timing. To address this, we conducted a multimodal synthesis of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies of ketamine in adults with treatment-resistant depression, integrating region-level inspection and functional network mapping to evaluate patterns across heterogeneous designs. The findings suggest that ketamine-related effects were frequently reported in subcortical regions, alongside more distributed and context-dependent effects across cortical systems, including prefrontal and anterior cingulate regions. Network-level summaries further suggested involvement of default-mode, ventral attention, and visual systems. Given variability in imaging modality, task state, and scan timing, these results should be interpreted as hypothesis-generating and motivate future harmonized multimodal studies designed to directly link circuit-level changes to molecular mechanisms and clinical response.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.