Volumetric Deficit Within the Fronto-Limbic-Striatal Circuit in First-Episode Drug Naive Patients With Major Depression Disorder

Background: Depression is a major psychiatric disorder and the leading cause of disability worldwide. Previous evidence suggested certain pattern of structural alterations were induced by major depression disorder (MDD) with heterogeneity due to patients' clinical characteristics and proposed that early impairment of fronto-limbic-striatal circuit was involved. Yet the hypothesis couldn't be replicated fully. Accordingly, this study aimed to validate this hypothesis in a new set of first-episode, drug naive MDD patients and further explore the neuroimaging biomarker of illness severity using whole-brain voxel-based morphometry (VBM). Materials and Methods: A total of 93 participants, 30 patients with first-episode medication-naive MDD, and 63 healthy controls were enrolled in the study. VBM was applied to analyze differences in the gray matter volume (GMV) between these two groups. The correlation between the GMV of the identified brain regions and the severity of clinical symptoms quantified by the Hamilton Depression Scale (HAMD) was further conducted in the post-hoc analysis to confirm the role of GMV structural alteration in clinical symptoms. Results: Our results revealed that the brain gray matter volume of the prefrontal lobe, limbic system, striatum, cerebellum, temporal lobe, and bilateral lingual gyri were significantly decreased in MDD patients compared with healthy controls. Besides, the HAMD scores were negatively correlated with GMV of the right insula and positively correlated with that of the right lingual gyrus. Conclusions: Our findings provide robust evidence that gray matter structural abnormalities within the prefronto-limbic-striatal circuit are implicated in the pathophysiology of MDD at an early stage without confounding influence of medication status. Besides, our data suggest that the cerebellum, lingual gyrus, and fusiform gyrus should also be integrated into the brain alterations in MDD. Future synthesis of individual neuroimaging studies and more advanced statistical analysis comparing subfields of the aforementioned regions are warranted to further shed light on the neurobiology of the disease and assist in the diagnosis of this burdensome disorder.