Higher cortisol levels due to a hyperactive hypothalamic–pituitary–adrenal axis have been reported in patients with major depressive disorder (MDD). Increased cortisol levels change both the brain morphology and function in MDD patients. The multivariate source-based morphometry (SBM) technique has been applied to investigate neuroanatomical changes in some neuropsychiatric diseases, but not MDD. We aimed to examine the alterations in gray matter (GM) networks and their relationship with serum cortisol levels in first-episode, drug-naïve MDD patients using SBM. Forty-two patients with MDD and 39 controls were recruited via interviews. Morning serum cortisol levels were measured, and high-resolution T1-weighted imaging followed by SBM analysis was performed in all participants. The patients had significantly higher serum cortisol levels than the controls. We found two GM sources, which were significantly different between patients with MDD and controls (prefrontal network, p < .01; insula-temporal network, p < .01). Serum cortisol levels showed a statistically significant negative correlation with the loading coefficients of the prefrontal network (r = − 0.354, p = 0.02). In conclusion, increased serum cortisol levels were associated with reductions in the prefrontal network in the early stage of MDD, and SBM may be a useful approach for analyzing structural MRI data.

Objective: Hippocampal volume is reduced in patients with major depressive disorder (MDD) compared with healthy controls. The hippocampus is a limbic structure that has a critical role in MDD. The aim of the present study was to investigate the changes in the volume of the hippocampus and its subfields in MDD patients who responded to antidepressants and subsequently were in continuous remission. Subjects and Methods: Eighteen patients who met the following criteria were enrolled in the present study: the DSM-IV-TR criteria for MDD, drug-naïve at least 8 weeks or more, scores on the 17-items of Hamilton Rating Scale for Depression (HAMD) of 14 points or more, and antidepressant treatment response within 8 weeks and continuous remission for at least 6 months. All participants underwent T1-weighted structural MRI and were treated with antidepressants for more than 8 weeks. We compared the volumes of the hippocampus, including its subfields, in responders at baseline to the volumes at 6 months. The volumes of the whole hippocampus and the hippocampal subfields were measured using FreeSurfer v6.0. Results: The volumes of the left cornu Ammonis (CA) 3 (p = 0.016) and the granule cell layer of the dentate gyrus (GC-DG) region (p = 0.021) were significantly increased after 6 months of treatment compared with those at baseline. Conclusions: Increases in volume was observed in MDD patients who were in remission for at least 6 months.