Altered gray-white matter contrast in early adulthood major depressive disorder: A partial reflection of structural...

Early-adult major depressive disorder (MDD) is linked to widespread cortical thickness (CT) reduction and white matter microstructural abnormalities. Gray-white matter contrast (GWC), reflecting both gray and white matter properties, remains understudied in this population.

This study included 365 early-adult MDD patients and 234 healthy controls (HC), all undergoing T1-weighted structural MRI and diffusion-weighted MRI. GWC and CT were derived from T1 images, while fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were extracted from diffusion data. Whole-brain and region-of-interest analyses were conducted to compare group differences, and their associations with clinical and cognitive measures were evaluated: Visual Reproduction (VR), Digit Span Forward (DSF), Digit Span Backward (DSB).

Compared to HC, MDD patients showed increased GWC in multiple regions, reduced CT in some areas, and altered FA, MD, and RD. In regions with elevated GWC, the left insula showed reduced CT, increased MD and RD, with GWC positively correlated with CT and negatively with VR. The left middle temporal gyrus had decreased CT; the left parahippocampal gyrus showed reduced FA; both positively correlated with GWC, and the latter positively correlated with DSF and DSB. The right lingual gyrus had decreased RD, positively correlated with DSB.

GWC may serve as a potential biomarker of early structural abnormalities in MDD. The left insula, parahippocampal, right lingual and middle temporal gyrus may be involved in early MDD pathology, with the first three linked to cognitive impairment.