The present study aimed to use surface-based morphometric analysis to characterize the alteration of cortical thickness in untreated, first-episode adult patients with major depressive disorder (MDD) and whether such cortical thickness deficits were related with clinical symptom severity as well as disease duration.In a cross-sectional design, high-resolution T1-weighted images using a volumetric 3D Spoiled Gradient Recall sequence were acquired from 37 first-episode never-medicated adult MDD patients (M/F=25/12, mean age 26.70±7.11 years) and 41 age, sex and educational years well-matched healthy controls (M/F=26/15, mean age 27.15±7.20 years). Freesurfer was used to preprocess the raw data and calculate the cortical thickness. Cortical thickness was compared in the two groups and correlated with clinical symptom severity as well as untreated disease duration in the patient group.Freesurfer analysis on Qdec revealed significantly increased cortical thickness (p < 0.05, False Discovery Rate) in left anterior and posterior cingulate cortex extending to medial superior frontal cortex, bilateral precentral cortex, left paracentral cortex, bilateral superior parietal cortex, left temporal poles, and right lateral occipital cortex in first-episode never-medicated MDD patients compared to healthy controls (Figure 1). No region with significantly decreased cortical thickness was found in MDD patients. In addition, clinical symptom severity and untreated disease duration showed no correlation with the cortical thickness abnormalities in MDD patients group.The mechanisms that account for the increased thickness of neocortex in MDD are not yet clear, one plausible explanation for this effect is that it may be related to an inflammatory response characterized by cellular hypertrophy, astrocyte proliferation, process extension and interdigitation^1,2, representing a compensatory effect in the early stage of depression³. Of note is that no decreased cortical thickness was found in present study that only included first-episode patients. Hence, our findings do not per se contradict later thinning as a function of progressive neurotoxic effects on the anterior cingulate cortex ⁴. Another speculative explanation is that the greater thickness may be the first evidence of an underlying pathological process, which eventually leads to volumetric reduction⁵ when these compensatory mechanisms are unable to prevent the accumulation of extracellular glutamate in the longer run ¹.