Subtyping drug-free first-episode major depressive disorder based on cortical surface area alterations

Major depressive disorder (MDD) is recognized as a complex and heterogeneous metal illness, characterized by diverse clinical symptoms and variable treatment outcomes. Previous studies have repeatedly reported alterations in brain morphology in MDD, but findings vary across sample characteristics. Whether this neurobiological substrate could stratify MDD into more homogeneous clinical subgroups thus improving personalized medicine remains unknown.

We included 65 drug-free patients with first-episode MDD and 66 healthy controls (HCs) and collected their structural MRI data. We performed the surface reconstruction and calculated cortical surface area using Freesurfer. The surface area of 34 Gy matter regions in each hemisphere based on the Desikan-Killiany atlas were extracted for each participant and subtyping results were obtained with the Louvain community detection algorithm. The demographic and clinical characteristics were then compared between MDD subgroups.

Two subgroups defined by distinct patterns of cortical surface area were identified in first-episode MDD. Subgroup 1 exhibited a significant reduction in surface area across nearly the entire cortex compared to subgroup 2 and HCs, whereas subgroup 2 demonstrated increased surface area than HCs. Further, subgroup 1 exhibited a higher proportion of females, and higher severity of anxiety symptoms compared to subgroup 2.

The relatively small sample size.

This study identified two neurobiologically subgroups with distinct alterations in cortical surface area among drug-free patients with first-episode MDD. Our results highlight the promise of in delineating morphological heterogeneity within MDD, particularly in relation to the severity of anxiety symptoms.