Neuroanatomical Correlates of Mild-to-Moderate Depression: Memory Ability Mediates the Association Between Gray Matter Volume and Antidepressant Treatment Outcome

Mild-to-moderate depression (MMD) is frequently encountered in clinical practice. Investigating the brain mechanism and its relationship with symptoms in patients with MMD can help us understand the occurrence and development of depression, thus optimizing the prevention and treatment of depression. Shugan Jieyu capsule (SG), a traditional Chinese medicine, is commonly used to ameliorate emotional and cognitive symptoms induced by patients with MMD. Combining clinical assessments and magnetic resonance imaging (MRI), we obtained the emotional and cognitive status of MMD patients and also explored the structural and functional alterations in MMD patients after SG treatments. Structural MRI demonstrated that the gray matter volumes of the left thalamus, right thalamus, and right amygdala in MMD patients were significantly smaller than in healthy controls, and the right amygdala volume was negatively related to depression symptoms in MMD patients. Resting-state functional MRI data demonstrated that MMD patients exhibited decreased temporal coupling between the right amygdala and nucleus accumbens, which was further associated with the severity of depression. Furthermore, right amygdala volume at baseline served as a significant predictor to identify the treatment outcome after 8 weeks of SG treatment in the patients' group, and importantly, the memory ability mediated the relationship from right amygdala volume to the treatment outcome. These data revealed the structural and functional deficits in the right amygdala, which were highly correlated with the symptoms of depression and its cognitive ability, likely predicting treatment outcome. Therefore, this study strengthened our understanding of the pathogenesis of MMD, which is hoped that it will contribute to tailoring a personalized method for treating the patients.