Neuroimaging studies on major depressive disorder (MDD) have identified an extensive range of brain structural abnormalities, but the exact neural mechanisms associated with MDD remain elusive. Most previous studies were performed with voxel- or surface-based morphometry which were univariate methods without considering spatial information across voxels/vertices.

Brain morphology was investigated using voxel-based morphometry (VBM) and source-based morphometry (SBM) in 1082 MDD patients and 990 healthy controls (HCs) from the REST-meta-MDD Consortium. We first examined group differences in regional grey matter (GM) volumes and structural covariance networks between patients and HCs. We then compared first-episode, drug-naïve (FEDN) patients, and recurrent patients. Additionally, we assessed the effects of symptom severity and illness duration on brain alterations.

VBM showed decreased GM volume in various regions in MDD patients including the superior temporal cortex, anterior and middle cingulate cortex, inferior frontal cortex, and precuneus. SBM returned differences only in the prefrontal network. Comparisons between FEDN and recurrent MDD patients showed no significant differences by VBM, but SBM showed greater decreases in prefrontal, basal ganglia, visual, and cerebellar networks in the recurrent group. Moreover, depression severity was associated with volumes in the inferior frontal gyrus and precuneus, as well as the prefrontal network.

Simultaneous application of VBM and SBM methods revealed brain alterations in MDD patients and specified differences between recurrent and FEDN patients, which tentatively provide an effective multivariate method to identify potential neurobiological markers for depression.

Imaging studies have shown that the subcallosal region (SCR) volume was decreased in patients with major depressive disorder (MDD). However, whether the volumetric reductions in the SCR are due to thinning of the cortex or a loss of surface area (SA) remains unclear. In addition, the relationship between cortical measurements of the SCR and age through the adult life span in MDD remains unclear.

We used a cross-sectional design from 114 individuals with MDD and 112 matched healthy control (HC) individuals across the adult life span (range: 18–74 years). The mean cortical volume (CV), SA and cortical thickness (CT) of the SCR were computed using cortical parcellation based on FreeSurfer software. Multivariate analyses of covariance models were performed to compare differences between the MDD and HC groups on cortical measurements of the SCR. Multiple linear regression models were used to test age-by-group interaction effects on these cortical measurements of the SCR.

The MDD had significant reductions in the CV and SA of the left SCR compared with HC individuals after controlling of other variables. The left SCR CV and SA reductions compared with matched controls were observed only in early adulthood patients. We also found a significant age-related CT reduction in the SCR both in the MDD and HC participants.

The SCR volume reduction was mainly driven by SA in MDD. The different trajectories between the CT and SA of the SCR with age may provide valuable information to distinguish pathological processes and normal ageing in MDD.