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Brain changes associated with depression treatment: a meta-analysis

Gianna M. Perez, Benjamin M. Rosenberg, Wenyi Xu, Desmond J. Oathes

NeuroImage: Clinical 2025 DOI: 10.1016/j.nicl.2025.103874 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Meta-analysis Peer reviewed
Sample size 302
Population Depressed subjects
Interventions pharmacology psychotherapy electroconvulsive therapy psilocybin ketamine
Topics Depression
Citations 3
Key findings The right amygdala showed a consistent decrease in activity following effective depression treatment across multiple treatment types.

Abstract

Background: Understanding changes in brain activity following treatment is critical to advancing the use of neuroimaging in psychiatric research. Previous work has focused on defining abnormalities (biomarkers) between patients and healthy controls but there has been less investigation of brain changes in depression patients following treatment. To boost sample size and explore the possibility of common treatment mechanisms, we considered results from standard and emerging forms of treatment. In order to investigate and synthesize findings of brain changes, we conducted a coordinate based meta-analysis of depression treatment studies reporting pre- and post-treatment task-based neuroimaging data to determine if there were common brain regions that changed with effective depression treatment across treatment types.

Methods: Activation likelihood estimation was performed to synthesize the imaging results. The meta-analysis included data from 302 depressed subjects yielding 87 foci across 18 experiments. The studies examined various depression treatments including pharmacology, psychotherapy, electroconvulsive therapy, psilocybin, and ketamine with brain activity measures in response to emotion tasks in the scanner.

Results: Across studies, the right amygdala (peak MNI coordinates [30, 2, -22]) was a region of convergence, reflecting a consistent change in activity following depression treatment. Follow-up analyses suggested that this finding was driven by right amygdala activity decreasing with treatment.

Conclusions: Our result, focusing on within-patient changes associated with treatment, highlights the right amygdala as a brain area especially relevant to depression treatment measured with fMRI. This finding provides a lens to focus depression biomarker research based on imaging measures that track depression treatment effects.

Comparable studies

Other systematic reviews and meta-analyses on depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... 2020 Systematic review n = 188

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