Ketamine-related neural changes in treatment-resistant depression: A multimodal synthesis of fMRI and PET studies.

Ketamine's rapid antidepressant effects in treatment-resistant depression are linked to changes in brain activity, but previous studies have been hard to compare due to differences in imaging techniques, analysis methods, and timing. A review combining fMRI and PET studies found that ketamine-related effects commonly appear in subcortical brain regions, with more variable effects in cortical areas like the prefrontal and anterior cingulate cortices. Network-level patterns suggest involvement of the default-mode, ventral attention, and visual systems. These findings are hypothesis-generating and highlight the need for future studies that harmonize methods to directly connect circuit changes to molecular mechanisms and clinical outcomes.

Study at a glance

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.