Brain volume abnormalities in major depressive disorder: A meta‐analysis of magnetic resonance imaging studies

Koolschijn, P. Cédric M.P.; van Haren, Neeltje E.M.; Lensvelt‐Mulders, Gerty J.L.M.; Hulshoff Pol, Hilleke E.; Kahn, René S.

doi:10.1002/hbm.20801

Cited by 902Treatment of Major DepressionNeural and Behavioral Psychology StudiesFunctional Brain Connectivity Studies

Brain volume abnormalities in major depressive disorder: A meta‐analysis of magnetic resonance imaging studies

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Koolschijn, P. Cédric M.P., van Haren, Neeltje E.M., Lensvelt‐Mulders, Gerty J.L.M., Hulshoff Pol, Hilleke E., Kahn, René S.·2009·Human Brain Mapping

DOI 10.1002/hbm.20801PMC PMC6871089

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Abstract

Objective. So far, there have been no attempts to integrate the growing number of all brain volumetric magnetic resonance imaging studies in depression. In this comprehensive meta‐analysis the magnitude and extent of brain volume differences between 2,418 patients with major depressive disorder and 1,974 healthy individuals from 64 studies was determined. Methods. A systematic research was conducted for volumetric magnetic resonance imaging studies of patients with major depressive disorder in relation to healthy control subjects. Studies had to report sufficient data for computation of effect sizes. For each study, the Cohen's d was calculated. All analyses were performed using the random effects model. Additionally, meta‐regression analyses were done to explore the effects of potential sources of heterogeneity. Results. Patients showed large volume reductions in frontal regions, especially in the anterior cingulate and orbitofrontal cortex with smaller reductions in the prefrontal cortex. The hippocampus, the putamen and caudate nucleus showed moderate volume reductions. Conclusions. This is the first comprehensive meta‐analysis in major depressive disorder demonstrating structural brain abnormalities, particularly in those brain areas that are involved in emotion processing and stress‐regulation. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.

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An early meta-analysis of 64 structural MRI studies reported that frontal regions showed the largest volumetric reductions in major depressive disorder, particularly in the anterior cingulate cortex and bilateral orbitofrontal cortex.
“An early meta-analysis (64 structural MRI studies) reported that frontal regions showed the largest volumetric reductions in MDD [78], particularly in the ACC and bilateral OFC, although distinct subregions were not investigated (see also [79]).”
From Prefrontal cortex and depression (2022) · cites this paper as [78]
Meta-analyses report moderate effect sizes, with Cohen's d from −0.41 to −0.47, for smaller hippocampal volume in major depressive disorder.
“These meta-analyses have reported moderate effect sizes for reduced hippocampal volume in MDD (Cohen’s d range = −0.41 to −0.47; 6,8,9).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [6]
Meta-analyses indicate that people with major depressive disorder have smaller hippocampal and medial prefrontal cortex volumes than healthy controls, including dorsal and ventral mPFC regions extending into medial orbitofrontal cortex and dorsal/rostral anterior cingulate cortex.
“several meta-analyses have demonstrated that, relative to healthy controls (HCs), individuals with MDD show reduced hippocampus and mPFC volumes, including dorsal and ventral mPFC portions (dmPFC/vmPFC) extending into the medial orbital frontal cortex (mOFC) as well as dorsal and rostral portions of the anterior cingulate cortex (rACC/dACC) (2,4–14).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [6]
Extracellular glutamate release outpaces clearance by glial cells, and the ensuing inflammation and neurodegeneration likely contribute to acute volume reductions and other cytoarchitectural abnormalities detected in depressed patients' brains.
“As extracellular glutamate release outpaces clearance by glial cells, and the ensuing inflammation and neurodegeneration likely contribute to the acute volume reductions and other cytoarchitectural abnormalities detected in depressed patients’ brains [35].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [35]
Meta-analyses revealed that depressed patients showed large volume reductions in frontal regions, especially in the anterior cingulate and orbitofrontal cortex.
“Meta-analyses revealed that depressed patients showed large volume reductions in frontal regions, especially in the anterior cingulate and OFC (Koolschijn et al., 2009; Lorenzetti et al., 2009).”
From The orbitofrontal cortex: reward, emotion and depression (2020) · cites this paper as Koolschijn et al., 2009

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Authors: Koolschijn, P. C. M. P., van Haren, N. E. M., Lensvelt‐Mulders, G. J. L. M., Hulshoff Pol, H. E., & Kahn, R. S.
Affiliations: University Medical Center Utrecht (NL)
Utrecht University (NL)
ORCID: Koolschijn, P. Cédric M.P.
Lensvelt‐Mulders, Gerty J.L.M.
Kahn, René S.
Venue: Human Brain Mapping
Publisher: Wiley
Published: 2009-05-13
Volume: 30
Issue: 11
Pages: 3719-3735
ISSN: 1065-9471 (ISSN-L)
1097-0193
DOI: 10.1002/hbm.20801
PMC: PMC6871089
OpenAlex: W1990168531
Cited by: 902
References: 209
Citations by year: 2026: 34 · 2025: 34 · 2024: 44 · 2023: 46 · 2022: 47 · 2021: 74 · 2020: 52 · 2019: 71 · 2018: 47 · 2017: 59 · 2016: 53 · 2015: 63 · 2014: 66 · 2013: 55 · 2012: 57
FWCI: 5.37
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Human Brain Mapping (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Keywords: major depressive disorder, brain volume, structural brain abnormalities, frontal lobe, anterior cingulate cortex, orbitofrontal cortex, prefrontal cortex, hippocampus, putamen, caudate nucleus, emotional processing, stress regulation
MeSH terms: Brain, Brain Mapping, Major Depressive Disorder, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Databases, Bibliographic

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Brain volume abnormalities in major depressive disorder: A meta‐analysis of magnetic resonance imaging studies

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