Replicating Neuroimaging Abnormalities in Major Depression

Convergent abnormalities were observed in secondary analyses across portions of the amygdala, hippocampus, subgenual cingulate cortex, and putamen.

Spatially convergent structural and functional abnormalities are observed in neuroimaging of patients with major depressive disorder (MDD), according to results from a meta-analysis published in the American Journal of Psychiatry. These findings indicate that major depression is associated with replicable neuroimaging features, beyond the transdiagnostic effects inscribed in previous meta-analyses.

Neuroimaging studies of depression and other psychiatric disorders have proliferated with the increased availability of magnetic resonance imaging (MRI) and other research techniques. However, the reliability of the neuroimaging literature has been challenged, mainly due to the use of small sample sizes, clinical heterogeneity, and problems related to correcting for multiple comparisons and inflated false positive rates.

Jodie P. Gray, MS, of the Research Imaging Institute, University of Texas Health Science Center at San Antonio, and colleagues performed the analyses. The study was a coordinate-based meta-analysis of 92 voxel-based morphometry (VBM) studies and resting-state voxel-based pathophysiology (VBP) studies that included a total of 2928 patients with MDD. The studies examined blood flow, glucose metabolism, regional homogeneity, and amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF).

There were 3 main meta-analytic classes that grouped input data: gray matter atrophy, increased function, and decreased function in patients with MDD vs healthy controls. Input data were then grouped across primary categories in secondary meta-analyses, whereas in the third analyses, the data were grouped by medication status and lack of a psychiatric comorbidity.

Across all studies, a total of 152 experiments were performed. There was no convergence across studies in the primary analyses. Convergent abnormalities were observed in secondary analyses across portions of the amygdala, hippocampus, subgenual cingulate cortex, and putamen. In the tertiary analyses, the investigators observed improved convergence compared with the secondary analyses.

According to the investigators, the study was limited by the enrollment of clinically heterogeneous groups of patients with MDD at the individual study level.

In spite of this limitation, the researchers wrote that their “analysis of clinical heterogeneity within this meta-analysis suggests that diverse patient populations may present significant confounders in neuro-imaging findings in major depression.” They also noted that the results indicate “the presence of major depression–associated brain features, in contrast to lack of disease-specific findings from previous transdiagnostic and major depression–specific meta-analyses.”


Gray JP, Müller VI, Eickhoff SB, Fox PT. Multimodal abnormalities of brain structure and function in major depressive disorder: A meta-analysis of neuroimaging studies. Am J Psychiatry. 2020;177(5):422-434.