Altered Structural Covariance Among the Dorsolateral Prefrontal Cortex and Amygdala in Treatment-Naïve Patients With Major Depressive Disorder

Background: Impairments in cognitive and emotional processing are a characteristic of major depressive disorder (MDD), and the dorsolateral prefrontal cortex (DLPFC) and amygdala are involved in these processes. However, the structural covariance between these two areas in patients with MDD has not been examined. Whether anatomical patterns are further damaged or compensated in untreated multiple-episode MDD compared to those in first-episode MDD is unclear. Methods: Structural magnetic resonance imaging was performed in 35 treatment-naïve, currently depressed patients with MDD and 35 age-, sex-, and education-matched controls. The cortical thickness and subcortical volume were calculated using FreeSurfer software. Patients were divided into two subgroups based on the previous number of episodes. Results: Regional abnormalities in patients with MDD were primarily observed in the frontal-limbic circuits. The negative structural association between the left DLPFC and left amygdala and the positive structural association between the bilateral DLPFC observed in controls were absent in patients with MDD. The medial orbitofrontal cortex and posterior cingulate cortex were thicker in patients with multiple-episode MDD than in patients with first-episode MDD and were positively correlated with disorder duration. No structural alterations were correlated with symptom severity. Conclusions: These findings may provide structural evidence for deficits in functional networks in MDD and supports an underlying structural mechanism of dysfunction involving top-down or bottom-up processes. Morphological abnormalities in the medial orbitofrontal cortex and posterior cingulate cortex may be critical for the pathophysiological progression of multiple-episode MDD.