Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Sep 6;3:332-9.
doi: 10.1016/j.nicl.2013.08.016. eCollection 2013.

Widespread Reductions in Gray Matter Volume in Depression

Free PMC article

Widespread Reductions in Gray Matter Volume in Depression

Stuart M Grieve et al. Neuroimage Clin. .
Free PMC article


Abnormalities in functional limbic-anterior cingulate-prefrontal circuits associated with emotional reactivity, evaluation and regulation have been implicated in the pathophysiology of major depressive disorder (MDD). However, existing knowledge about structural alterations in depression is equivocal and based on cohorts of limited sample size. This study used voxel-based morphometry (VBM) and surface-based cortical thickness to investigate the structure of these circuits in a large and well-characterized patient cohort with MDD. Non-geriatric MDD outpatients (n = 102) and age- and gender-matched healthy control participants (n = 34) provided T1-weighted magnetic resonance imaging data during their baseline visit as part of the International Study to Predict Optimized Treatment for Depression. Whole-brain VBM volumetric and surface-based cortical thickness assessments were performed voxel-wise and compared (at p < 0.05 corrected for multiple comparisons) between the MDD and control groups. MDD participants had reduced gray matter volume in the anterior cingulate cortex, regions of the prefrontal circuits, including dorsolateral and dorsomedial prefrontal cortices, and lateral and medial orbitofrontal cortices, but not in limbic regions. Additional reductions were observed cortically in the posterior temporal and parieto-occipital cortices and, subcortically in the basal ganglia and cerebellum. Focal cortical thinning in the medial orbitofrontal cortex was also observed for the MDD group. These alterations in volume and cortical thickness were not associated with severity of depressive symptoms. The findings demonstrate that widespread gray matter structural abnormalities are present in a well-powered study of patients with depression. The patterns of gray matter loss correspond to the same brain functional network regions that were previously established to be abnormal in MDD, which may support an underlying structural abnormality for these circuits.

Keywords: AAL, Automated Anatomical Labeling; ACC, Anterior Cingulate Cortex; BAs, Brodmann Areas; CVNA, Change in Volume expected in that region through Normal Aging; Cortical thickness; DLPFC, Dorsolateral Prefrontal Cortex; DTI, Diffusion Tensor Imaging; FDR, False Discovery Rate; GM, Gray Matter; Gray matter; HRSD17, 17-Item Hamilton Rating Scale for Depression; MDD, Major Depressive Disorder; MPFC, Medial Prefrontal Cortex; MRI, Magnetic Resonance Imaging; Major depressive disorder; OFC, Orbitofrontal Cortex; PFC, Prefrontal Cortex; VBM; VBM, Voxel-Based Morphometry; Volume; fMRI, functional Magnetic Resonance Imaging; iSPOT-D; iSPOT-D, International Study to Predict Optimized Treatment in Depression.


Fig. 1
Fig. 1
Voxel based morphometry volume differences between the MDD and control groups (MDD < controls at p < 0.05 FDR-corrected). The dominant three bilateral clusters are shown in two axial slices (columns 1 & 2), one coronal slice (column 3) and one sagittal slice (column 4) (the location of the axial and coronal slices is marked on the sagittal slice for reference): (top row) cluster 1 — 1a — dorsolateral prefrontal cortex, 1b — lateral orbitofrontal cortex, 1c — precentral gyrus; (middle row) cluster 2 — 2a — gyrus rectus, 1b — anterior cingulate cortex, 1c — posterior cingulate cortex, 1d — precuneus; and (bottom row) cluster 3 — 3a — fusiform gyrus, 3b — inferior temporal gyrus, 3c — middle temporal gyrus and 3d — superior temporal gyrus. Abbreviations: FDR, False Discovery Rate; MDD, Major Depressive Disorder.

Similar articles

See all similar articles

Cited by 97 articles

See all "Cited by" articles


    1. Arnone D. Magnetic resonance imaging studies in unipolar depression: systematic review and meta-regression analyses. Eur. Neuropsychopharmacol. 2012;22:1–16. - PubMed
    1. Ashburner J. A fast diffeomorphic image registration algorithm. NeuroImage. 2007;38(1):95–113. - PubMed
    1. Ballmaier M. Mapping brain size and cortical gray matter changes in elderly depression. Biol. Psychiatry. 2004;55:382–389. - PubMed
    1. Bora E. Gray matter abnormalities in major depressive disorder: a meta-analysis of voxel based morphometry studies. J. Affect. Disord. 2011;138:9–18. - PubMed
    1. Bora E. Meta-analysis of volumetric abnormalities in cortico–striatal–pallidal–thalamic circuits in major depressive disorder. Psychol. Med. 2012;42:671–681. - PubMed

LinkOut - more resources