Baseline cortical structural features are associated with depressive and cognitive improvement in major depressive disorder

Abstract Background Major depressive disorder (MDD) exhibits substantial clinical and neurobiological heterogeneity, along with marked variability in treatment response, underscoring the need for objective neuroimaging markers to inform personalized interventions. Methods Twenty-two patients with MDD and twenty-one age- and sex-matched healthy controls (HCs) were enrolled. Depressive symptoms were assessed using the 17-item Hamilton Rating Scale for Depression (HAMD17), and the Hamilton Rating Scale for Anxiety (HAMA), while cognitive function was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Structural magnetic resonance imaging (sMRI) was performed to assess cortical features in MDD patients and HCs. Cortical morphological features [fractal dimension (FD), gyrification index (GI), sulcus depth (SD), and cortical thickness (CT)] were quantified using the automated Computational Anatomy Toolbox (CAT12). Multiple regression analyses were conducted to identify cortical regions in which baseline morphology was associated with subsequent depressive and cognitive changes, controlling for age and sex (voxel-wise p < 0.001, family wise error corrected cluster-level p < 0.05). To further assess the stability and potential out-of-sample consistency of these associations, exploratory leave-one-out cross-validation (LOOCV) analyses with permutation testing were performed. Results Baseline FD in the left superior frontal cortex (SFC), left cuneus, right rostral middle frontal cortex and right lateral occipital cortex (LOC), GI in the left LOC, and CT in the bilateral insula and pericalcarine cortex were significantly associated with greater improvement in depressive symptoms following antidepressant treatment. In addition, lower baseline SD in the left LOC was associated with greater improvement in delayed memory. Single-ROI models (adjusted for age and sex) revealed that baseline left cuneus FD and left SFC FD was significantly correlated with changes in HAMD17 and HAMA, respectively, and the baseline left LOC/lingual SD showed a moderate cross-validated correlation with delayed memory change. These associations were supported by permutation testing, whereas the model for memory improvement showed only exploratory, non-significant cross-validated performance. Conclusions Baseline cortical morphometric features were associated with clinical and cognitive changes following antidepressant treatment in MDD. Single-ROI LOOCV models based on left cuneus and left SFC FD showed cross-validated associations with symptom improvement. These findings are preliminary and should be interpreted with caution, pending replication in independent cohorts.