Network localization of brain functional effects of ketamine treatment for major depression.
Haining Ma, Huaigui Liu, Wenwei Zhang, Xufeng Zhao, Dan Zhang, Kaijie An, Yinfeng Qian, Jiajia Zhu
European psychiatry : the journal of the Association of European Psychiatrists February 13, 2026 DOI: 10.1192/j.eurpsy.2026.10164 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review with functional connectivity network mapping Longitudinal Peer reviewed |
|---|---|
| Sample size | 508 |
| Population | Depressed patients from 16 published ketamine neuroimaging studies, plus 1113 healthy and 255 depressed individuals from large-scale functional MRI datasets |
| Intervention | Ketamine |
| Topics | Depression Ketamine Esketamine |
| Keywords | MRI Brain network Functional connectivity |
| Key findings | Ketamine treatment was associated with increased functional connectivity in subcortical (caudate nucleus, thalamus) and default-mode (medial prefrontal cortex) networks, and decreased connectivity in limbic (temporal pole), subcortical (hippocampus, amygdala), and default-mode (lateral temporal cortex) networks. The authors propose that this network-level mapping may help explain ketamine's antidepressant effects and advance its clinical application. |
Abstract
Considerable effort has been devoted to investigate the neuroimaging correlates and predictors of antidepressant response to ketamine, yet inconsistency in the location and nature of the regional brain effects makes it difficult to unify this research. Despite the revolutionary notion that psychiatric therapeutics show network-level brain representations, investigations into network localization of brain functional effects of ketamine treatment are still lacking. We initially identified the locations of longitudinal brain functional alterations (increase and decrease separately) induced by ketamine treatment from 16 published studies with 508 depressed patients. By integrating these affected brain locations with large-scale functional MRI datasets from 1113 healthy and 255 depressed individuals, we then leveraged a novel functional connectivity network mapping approach to construct ketamine-induced hyper-functional and hypo-functional networks respectively. The hyper-functional network mainly involved the subcortical (caudate nucleus and thalamus) and default (medial prefrontal cortex) networks, while its hypo-functional counterpart predominantly implicated the limbic (temporal pole), subcortical (hippocampus and amygdala), and default (lateral temporal cortex) networks. Our findings may shed light on the neurobiological effects of ketamine from a network perspective, which might represent a crucial step toward fostering the clinical application of ketamine in antidepressant treatment.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.