Systematic review · 2026
Brain scan markers that may predict who responds to ketamine for depression
- Original title
- Predictors of responsiveness to ketamine: An updated systematic review of neuroimaging findings.
- Authors
- Kiani I, Cattarinussi G, Sambataro F, et al.
- Journal
- Journal of affective disorders, 2026
- Molecules
- Ketamine
- Conditions
- Depression, Treatment-resistant depression, Suicidal ideation
- Evidence grade
- Low
- Source
- Read the original paper
The question
Can brain imaging tell in advance which people with major depression are likely to improve after ketamine treatment?
What they did
The authors searched four research databases (PubMed, Embase, Scopus and Web of Science) for studies that used brain imaging to look for markers predicting response to ketamine in major depressive disorder and in suicidal thinking. Fifteen studies met their criteria. They summarized the findings by imaging type, including functional connectivity, diffusion MRI (which tracks the brain’s wiring), structural MRI (which measures the size of brain regions) and magnetic resonance spectroscopy (which measures brain chemicals).
What they found
Two brain areas came up repeatedly: the anterior cingulate cortex (ACC), involved in emotion and attention, and the amygdala, involved in processing threat and emotion. Stronger connections between the pregenual part of the ACC, the amygdala and other brain regions were often linked to better response to ketamine. Diffusion MRI showed responders had higher fractional anisotropy (a measure of white-matter wiring integrity) in the cingulum bundle, structural MRI linked larger hippocampus volume to better response, and spectroscopy found responders had a higher Glx/glutamate ratio in dorsomedial/dorsal anterolateral regions. Task-based imaging also found ACC activity predicted antidepressant response.
The fine print
The review reports no pooled number of participants, and the included studies differed widely in how depression was assessed, how long people were followed, what ketamine dose was used and how the scans were done. Findings of this kind are correlations, not proof that these brain features cause a better response, and none has been validated as a clinical test. This summary is based on the abstract only.
What it means
Certain brain imaging features, especially in the anterior cingulate cortex and amygdala, appear more often in people who respond to ketamine, but the evidence is early and too inconsistent to guide treatment decisions today.
Evidence grade: Low. A systematic review that summarizes 15 small, methodologically varied brain imaging studies without pooling the results statistically.
This summary is based on the study’s published abstract.