Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

In major depressive disorder (MDD), it is unclear to what extent structural brain changes are associated with depressive episodes or represent part of the mechanism by which the risk for illness is mediated. The aim of this study was to investigate whether structural abnormalities are related to risk for the development of MDD. We compared healthy controls with a positive family history for MDD (HC-FHP), healthy controls with no family history of any psychiatric disease (HC-FHN) and patients with MDD. Groups were age- and sex-matched. We analyzed data from high-resolution magnetic resonance imaging using voxel-based morphometry. We performed small volume corrections for our regions of interest (hippocampus, dorsolateral [DLPFC] and dorsomedial prefrontal cortex [DMPFC], anterior cingulate cortex [ACC] and basal ganglia) using a family-wise error correction (p < 0.05) to control for multiple comparisons. There were 30 participants in the HC-FHP group, 64 in the HC-FHN group and 33 patients with MDD. The HC-FHP group had smaller right hippocampal and DLPFC grey matter volumes compared with the HC-FHN group, and even smaller right hippocampal volumes compared with patients with MDD. In addition, the HC-FHP group exhibited smaller white matter volumes in the DLPFC and left putamen but also greater volumes in 2 areas of the DMPFC compared with the HC-FHN group. Patients with MDD exhibited smaller volumes in the ACC, DMPFC, DLPFC and the basal ganglia compared with healthy controls. The retrospective identification of family history might result in a bias toward unidentified participants in the control group at risk for MDD, diminishing the effect size. Volume reductions in the hippocampus and DLPFC might be associated with a greater risk for MDD. The HC-FHP group had smaller hippocampal volumes compared with patients with MDD, which is suggestive for neuroplastic effects of treatment. The HC-FHP group had not yet experienced a depressive episode and therefore might have been resilient and might have had some protective strategies. Whether resilience is associated with the larger white matter volumes in the DMPFC (e.g., owing to compensatory, neuroplastic remodelling mechanisms) needs to be confirmed in future studies.

Background: Childhood maltreatment has been found to play a crucial role in the development of psychiatric disorders. However, whether childhood maltreatment is associated with structural brain changes described for major depressive disorder (MDD) is still a matter of debate. The aim of this study was to investigate whether patients with MDD and a history of childhood maltreatment display more structural changes than patients without childhood maltreatment or healthy controls. Methods: Patients with MDD and healthy controls with and without childhood maltreatment experience were investigated using high-resolution magnetic resonance imaging (MRI), and data were analyzed using voxel-based morphometry. Results: We studied 37 patients with MDD and 46 controls. Grey matter volume was significantly decreased in the hippocampus and significantly increased in the dorsomedial prefrontal cortex (DMPFC) and the orbitofrontal cortex (OFC) in participants who had experienced childhood maltreatment compared with those who had not. Patients displayed smaller left OFC and left DMPFC volumes than controls. No significant difference in hippocampal volume was evident between patients with MDD and healthy controls. In regression analyses, despite effects from depression, age and sex on the DMPFC, OFC and hippocampus, childhood maltreatment was found to independently affect these regions. Limitations: The retrospective assessment of childhood maltreatment; the natural problem that patients experienced more childhood maltreatment than controls; and the restrictions, owing to sample size, to investigating higher order interactions among factors are discussed as limitations. Conclusion: These results suggest that early childhood maltreatment is associated with brain structural changes irrespective of sex, age and a history of depression. Thus, the study highlights the importance of childhood maltreatment when investigating brain structures.