Multimodal Abnormalities of Brain Structure and Function in Major Depressive Disorder: A Meta-Analysis of Neuroimaging Studies - PubMed (original) (raw)

Meta-Analysis

Multimodal Abnormalities of Brain Structure and Function in Major Depressive Disorder: A Meta-Analysis of Neuroimaging Studies

Jodie P Gray et al. Am J Psychiatry. 2020.

Erratum in

Abstract

Objective: Imaging studies of major depressive disorder have reported structural and functional abnormalities in a variety of spatially diverse brain regions. Quantitative meta-analyses of this literature, however, have failed to find statistically significant between-study spatial convergence, other than transdiagnostic-only effects. In the present study, the authors applied a novel multimodal meta-analytic approach to test the hypothesis that major depression exhibits spatially convergent structural and functional brain abnormalities.

Methods: This coordinate-based meta-analysis included voxel-based morphometry (VBM) studies and resting-state voxel-based pathophysiology (VBP) studies of blood flow, glucose metabolism, regional homogeneity, and amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF). Input data were grouped into three primary meta-analytic classes: gray matter atrophy, increased function, and decreased function in patients with major depression relative to healthy control subjects. In secondary meta-analyses, the data were grouped across primary categories, and in tertiary analyses, by medication status and absence of psychiatric comorbidity. Activation likelihood estimation was used for all analyses.

Results: A total of 92 publications reporting 152 experiments were identified, collectively representing 2,928 patients with major depressive disorder. The primary analyses detected no convergence across studies. The secondary analyses identified portions of the subgenual cingulate cortex, hippocampus, amygdala, and putamen as demonstrating convergent abnormalities. The tertiary analyses (clinical subtypes) showed improved convergence relative to the secondary analyses.

Conclusions: Coordinate-based meta-analysis identified spatially convergent structural (VBM) and functional (VBP) abnormalities in major depression. The findings suggest replicable neuroimaging features associated with major depression, beyond the transdiagnostic effects reported in previous meta-analyses, and support a continued research focus on the subgenual cingulate and other selected regions' role in depression.

Keywords: Major Depressive Disorder; Meta-Analysis; VBM; VBP; Voxel-Based Morphometry; Voxel-Based Pathophysiology.

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Figures

FIGURE 1.

FIGURE 1.. Flow diagram of study selection for a meta-analysis of neuroimaging studies in major depressive disordera

aThe literature search identified an overall data set of 92 independent publications reporting 152 experiments; five publications included investigations of both structural and functional changes, contributing a total of 97 “studies.” ALFF/fALFF=amplitude of low-frequency fluctuations (ALFF) and fractional ALFF; FDG-PET= fluorodeoxyglucose metabolism PET; MDD=major depressive disorder; PET=positron emission tomography; ROI=region of interest; SPECT=single-photon emission computed tomography; VBM=voxel-based morphometry; VPM=voxel-based pathophysiology; VBMneg=decreased gray matter volume relative to controls; VBPneg and VBPpos=decreased and increased function relative to controls, respectively.

FIGURE 2.

FIGURE 2.. Meta-analytic groups tested in a meta-analysis of neuroimaging studies in major depressive disordera

a First, a preliminary all-effects analysis of unified results across all imaging modalities was performed. Results from all experiments were concatenated into unified disease-control contrast groups ofVBMneg + VBPpos + VBPneg. Next, 18 different meta-analyses were performed, including the five major meta-analytic classes of decreased gray matter volume relative to controls (VBMneg), decreased (VBPneg) and increased (VBPpos) function relative to controls; each VBP group pooled with the gray matter volume group (VBPneg + VBMneg and VBPpos + VBMneg); and subgroups of each meta-analytic class comprising specific clinical populations for which the number of qualifying experiments exceeded 17. VBM=voxel-based morphometry; VBP=voxel-based pathophysiology.

FIGURE 3.

FIGURE 3.. Abnormal regions identified in a meta-analysis of neuroimaging studies in major depressive disordera

a Abnormal regions were identified from all-effects analysis and meta-analytic groupings of combined VBPpos and VBMneg, and VBPneg. Clinical subgroupings that also identified abnormal regions are shown. BA= Brodmann’s area; VBM=voxel-based morphometry; VBP=voxel-based pathophysiology; VBMneg=decreased gray matter volume relative to controls; VBPneg and VBPpos=decreased and increased function relative to controls, respectively.

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