Network localization of functional brain changes associated with ketamine's therapeutic effects in depression.
Shaoqiang Han, Ya Tian, Huiting Yang, Ruiping Zheng, Shuying Li, Keke Fang, Baohong Wen, Liang Liu, Yarui Wei, Yuan Chen, Huafu Chen, Jingliang Cheng, Yong Zhang
Biological Psychiatry June 13, 2025 DOI: 10.1016/j.biopsych.2025.06.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 614 |
| Population | Individuals with depression and healthy controls |
| Topics | Depression Ketamine Esketamine |
| Keywords | Ketamine: ketamine Therapeutic effects Unique power Depression: depression Lift depression Treating depression Mood Specific brain network Robust brain network Subgenual cingulate cortex Regions Alters functional connectivity |
| Citations | 1 |
| Key findings | Heterogeneous brain locations from ketamine studies converge on a robust, depression-specific functional brain network involving default mode, ventral attention, and frontoparietal regions, with a ketamine-specific circuit including the subgenual cingulate cortex and dorsolateral prefrontal cortex. |
Abstract
Although numerous studies have attempted to identify the functional pathways underlying the rapid antidepressant effects of ketamine, their findings remain inconsistent, limiting our understanding of the neural mechanisms involved. This study aims to delineate a specific brain circuit by integrating diverse functional findings related to ketamine's efficacy in depression. We conducted a systematic review of multimodal neuroimaging studies reporting brain locations associated with ketamine's effects on depression. Using functional connectivity network mapping and a large-scale normative connectome database, we mapped these locations onto a ketamine functional brain network. We tested the robustness of this network by evaluating its stability under parameter perturbations and leave-one-study-out validation, and assessed its specificity for depression relative to other mental disorders. We further identified the ketamine-specific brain circuit compared with an antidepressant functional brain network constructed using the same methodology. Our review included 18 multimodal neuroimaging studies with 440 depression individuals and 174 healthy controls. The heterogeneous brain locations localized to a connected network primarily involving regions implicated in the default mode, ventral attention, and frontoparietal networks. This network demonstrated robustness to minor perturbations and validation, and was specifically linked to depression. Compared with the antidepressant functional brain network, the ketamine-specific brain circuit predominantly encompassed brain regions such as the subgenual cingulate cortex and dorsolateral prefrontal cortex, which aligned with optimal brain stimulation sites for depression. These findings help reconcile seemingly inconsistent neuroimaging results and provide new insights into the neuropathology of ketamine's therapeutic effects from a network perspective.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.