Serum copper and zinc levels correlate with biochemical metabolite ratios in the prefrontal cortex and lentiform nucleus of patients with major depressive disorder

Background: Previous studies have demonstrated that copper and zinc metabolism are associated with the development of major depressive disorder (MDD). Abnormal copper and zinc levels may be related to neurotransmission and biochemical metabolism in the brains of MDD patients, especially in the prefrontal cortex (PFC) and lentiform nucleus (LN). However, the mechanism of how copper and zinc levels contribute to neural metabolism in MDD patients remains to be deciphered. This study aimed to correlate copper and zinc levels with biochemical metabolite ratios in the PFC and LN of MDD patients. Method: Twenty-nine MDD patients and thirty-two healthy control (HC) volunteers were enrolled in this study. Proton magnetic resonance spectroscopy (H-1-MRS) was used to determine the levels of the N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) in the brain, and specifically in the PFC and LN regions. Serum copper and zinc levels were measured using atomic emission spectrometry (AES). Afterwards, copper and zinc levels were correlated with biochemical metabolite ratios in the PFC and LN regions of the brain. Results: Higher serum copper and lower serum zinc levels with higher copper/zinc ratios were observed in MDD patients. NAA/Cr ratios in the PFC of MDD patients were lower compared to HC volunteers. In MDD patients, serum copper levels were negatively correlated with NAA/Cr ratios in the right PFC and right LN, while copper/zinc ratios were negatively correlated with NAA/Cr ratios in the right LN. No significant differences in serum copper and zinc levels with NAA/Cr ratios in the left PFC and left LN were observed in MDD patients. Conclusion: Our findings suggest that higher serum copper and lower serum zinc levels may contribute to neuronal impairment by affecting neuronal biochemical metabolite ratios in the right PFC and right LN of MDD patients. Abnormal copper and zinc levels may play an important role in the pathophysiology of MDD.