Increased serum homocysteine in first episode and drug-naïve individuals with schizophrenia: sex differences and correlations with clinical symptoms

Abstract

Background Accumulating evidence shows that homocysteine (Hcy) is implicated in the pathophysiology of schizophrenia, and plays an important role in clinical characteristics. This study evaluated the relationships between Hcy levels and clinical features in first-episode, Chinese Han, drug-naïve (FEDN) patients with schizophrenia. Methods FEDN individuals (119 with schizophrenia and 81 healthy controls matched for age, sex, education, and body mass index (BMI)) were enrolled. The serum Hcy levels were determined by enzyme cycle assay experiments. Severities of clinical symptoms were rated on the Positive and Negative Syndrome Scale (PANSS). Results FEDN individuals with schizophrenia had higher Hcy levels compared with healthy controls (F = 46.865, P < 0.001). Correlation analysis and multiple stepwise regression analyses showed that serum Hcy levels in FEDN schizophrenia individuals were positively correlated with PANSS general psychopathology subscale (r = 0.294, P = 0.001) and PANSS total score (r = 0.273, P = 0.003). No significant association was found between Hcy and age, BMI, PANSS positive subscale, and the PANSS negative subscale (all, P > 0.05). Male individuals had significantly higher serum Hcy levels than female individuals (F = 7.717, P = 0.006) after controlling for confounding factors (F = 0.759, P = 0.011). Conclusions Serum Hcy levels were increased in FEDN individuals with schizophrenia, and Hcy levels may be involved in pathophysiological mechanisms. Sex differences in Hcy levels were observed, with higher levels in male FEDN individuals compared to females.

Association of homocysteine with white matter dysconnectivity in schizophrenia

“…One explanation could be for this finding in terms of the clinical severity of SZ. Prior studies showed positive correlations between plasma Hcy levels and PANSS scores 11 – 13 , and we also confirmed a significant positive correlation of plasma Hcy levels with PANSS-total score and PANSS-general psychopathology subscale score. These findings suggest that a population with SZ of lower clinical severity may exhibit lower plasma Hcy levels.…”

“…A Mendelian randomization analysis yielded an odds ratio of 2.15 per 1-SD increase in plasma Hcy levels 10 . Additionally, several studies, including one conducted in drug-naïve, first-episode psychosis patients 11 , have reported that plasma Hcy levels are positively correlated with the clinical severity of SZ using the Positive and Negative Syndrome Scale (PANSS) 11 – 13 . Therefore, these findings implicate increased Hcy as a part of the biological etiology of SZ.…”

Correlation of Serum High-Sensitivity C-Reactive Protein, Homocysteine, and Macrophage Migration Inhibitory Factor Levels With Symptom Severity and Cognitive Function in Patients With Schizophrenia

“…Specifically, Hcy levels can be effectively reduced by B vitamin and folic acid supplementation, which may be beneficial for reducing SP-associated negative symptoms 23 . Zhilyaeva et al have observed that PANSS negative symptom scores, including difficulty with abstract thinking, lack of spontaneity and fluency in conversation, stereotyped thinking, and motor retardation, were more pronounced in SP patients with elevated Hcy levels, supporting the positive association between PANSS and high Hcy levels that we observed 24,25 . It has been also evaluated that patients with SP perform worse on cognitive assessments, and high levels of Hcy are associated with this 26–28 …”

“…23 Zhilyaeva et al have observed that PANSS negative symptom scores, including difficulty with abstract thinking, lack of spontaneity and fluency in conversation, stereotyped thinking, and motor retardation, were more pronounced in SP patients with elevated Hcy levels, supporting the positive association between PANSS and high Hcy levels that we observed. 24,25 It has been also evaluated that patients with SP perform worse on cognitive assessments, and high levels of Hcy are associated with this. [26][27][28] Some articles have shown an association between elevated Hcy levels and cognitive dysfunction in patients with SP.…”

Associations among plasma markers for N-methyl-d-aspartate receptor hypofunction, redox dysregulation, and insufficient myelination in patients with schizophrenia

“…Homocysteine is a component of one-carbon metabolism, which is involved in synthesizing methyl donors and the antioxidant glutathione (GSH). Thus, abnormalities in homocysteine may disturb normal methylation reactions, including DNA methylation, detoxification of xenobiotics via GSH conjugation, and redox regulation by GSH antioxidant activity [ 13 ]. In addition to the dysregulation of these signaling factors, cerebral volume is consistently reported to be lower in patients with schizophrenia [ 14 , 15 ], partly due to a reduction in myelin volume [ 16 ].…”