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It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N -acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC. • Serum levels of Cu and CER decreased in men with MDD, while the Cu/Zn ratio increased in women with MDD. • In males with MDD, a gender-specific decrease in the NAA/PCr + Cr ratio was noted in the left ACC. • The Cu/Zn ratio and Fe levels in male MDD patients are associated with changes in neurometabolism in the ACC. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) and insomnia have been linked to deficiencies in cognitive performance. However, the underlying mechanism of cognitive impairment in MDD patients with insomnia symptoms (IS) remains unclear. This study aimed to explore the effects of IS in patients with MDD by comparing cognitive function indices among those with IS, those without insomnia symptoms (NIS), and healthy controls (HCs). In addition, we assessed whether the dysfunction of central nervous system (CNS) is one of the important pathophysiologic mechanisms of IS in patients with MDD by comparing the biochemical metabolism ratios in the anterior cingulate cortex (ACC). Fifty-five MDD with IS, 39 MDD without IS, and 47 demographically matched HCs underwent the MATRICS Consensus Cognitive Battery (MCCB) assessment and proton magnetic resonance spectroscopy (1H-MRS). MCCB cognitive scores and biochemical metabolism in ACC were assessed and compared between groups. Compared to the HCs group, IS and NIS groups scored significantly lower in seven MCCB cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning problem solving and social cognition). IS group showed a lower speed of processing and lower Cho/Cr ratio in the left ACC vs. NIS group and HCs. Also, in IS group, the Cho/Cr ratio in the left ACC was positively correlated with the composite T -score. Patients with comorbidity of MDD with IS may exhibit more common MCCB cognitive impairments than those without IS, particularly speed of processing. Also, dysfunction of ACC may underlie the neural substrate of cognitive impairment in MDD with IS. • Major depressive disorder with insomnia symptoms suffered more common MCCB cognitive impairments and neuro dysfunction. • Using proton magnetic resonance spectroscopy to assess brain biochemical metabolism. • MDD patients with insomnia symptoms exhibited lower Cho/Cr ratio in left ACC. • Brain biochemical metabolism changes in ACC were correlated with cognitive function impairments in MDD with insomnia symptoms. [ABSTRACT FROM AUTHOR]

Objectives: Childhood trauma is a risk factor that may lead to persistent brain metabolic abnormalities, predisposing individuals to major depressive disorder (MDD). To better elucidate the pathogenesis of MDD, we investigated the neurometabolic changes in unmedicated MDD patients who had experienced childhood trauma (CT).Methods: In this study, 37 unmedicated MDD patients with CT, 35 unmedicated MDD patients without CT, and 30 healthy control participants underwent high-resolution proton magnetic resonance spectroscopy (1H-MRS) examination. Bilateral metabolic ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in the prefrontal white matter (PWM), anterior cingulate cortex (ACC), putamen, and cerebellum were obtained.Results: MDD patients showed neurometabolic changes in the cortico-striato-cerebellar (CSC) circuit. Furthermore, MDD patients showed significantly lower NAA/Cr and higher Cho/Cr ratio in the bilateral ACC and putamen, and higher NAA/Cr and lower Cho/Cr ratio in the cerebellum. Childhood trauma reduced the Cho/Cr ratio in the left ACC, which played an important role in longer and more episodes of depression.Conclusion: Early childhood trauma has a long-lasting impact on the metabolism of adult MDD patients, leading to abnormal choline metabolism of the left ACC. Abnormal biochemical metabolism in the CSC circuit may be an underlying pathophysiology of MDD.Limitation: As this is a small cross-sectional study, the impact of childhood trauma on the different stages of depression has not been observed. [ABSTRACT FROM AUTHOR]