# Network localization of brain functional effects of ketamine treatment for major depression

**Authors:** Haining Ma, Huaigui Liu, Wenwei Zhang, Xufeng Zhao, Dan Zhang, Kaijie An, Yinfeng Qian, Jiajia Zhu

PMC · DOI: 10.1192/j.eurpsy.2026.10164 · 2026-02-13

## TL;DR

This study identifies brain networks affected by ketamine treatment for depression, offering a network-level understanding of its effects.

## Contribution

The paper introduces a novel functional connectivity network mapping approach to analyze ketamine's brain effects.

## Key findings

- Ketamine induces hyper-function in subcortical and default mode networks.
- Hypo-function is observed in limbic, subcortical, and lateral temporal networks.
- The findings provide a network-level perspective on ketamine's neurobiological effects.

## 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.

## Linked entities

- **Chemicals:** ketamine (PubChem CID 3821)
- **Diseases:** major depression (MONDO:0002009)

## Full-text entities

- **Diseases:** major depression (MESH:D003865)
- **Chemicals:** ketamine (-)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12978991/full.md

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Source: https://tomesphere.com/paper/PMC12978991