The interplay between homocysteine, oxidative stress, and butyrylcholinesterase activity in the pathogenesis of schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is a serious mental illness linked to neurobiological problems, such as hyperhomocysteinemia (HHC), increased butyrylcholinesterase (BChE) activity, and a pro-oxidant status. However, it remains unclear how these different markers interact with each other. This study aimed to analyze oxidative status, Hcys, and BChE activity variations in male drug-free SCZ patients compared to healthy controls. METHODS: We conducted a case-control study on male drug-free patients with SCZ. Metabolic parameters, oxidative status, Hcys, BChE activity, and ultrasensitive C-reactive protein (CRP) were tested for both groups. RESULTS: CRP and BChE levels were significantly higher in SCZ. A significant positive correlation was identified between BChE activity and PANSS Positive and General scores. Patients had lower levels of folate and vitamin B12 and concurrently higher levels of Hcys compared to controls. A significant positive correlation was found between Hcys levels and the PANSS Positive (r = 0.423, p < 0.001) and Negative scores (r = 0.414, p < 0.001). The correlation matrix shows strong associations between Hcys and oxidative markers, namely, reduced glutathione (GSH) and malondialdehyde (MDA) levels. Using a binary logistic regression model, the occurrence of psychotic decompensation was independently associated with BChE, GSH, and MDA. CONCLUSION: This study offers valuable insights into the intricate cholinergic, oxidative, and inflammatory processes linked to SCZ, which further exacerbate the clinical symptoms into a vicious cycle. Elevated Hcys levels appear mainly as a consequence of folate and vitamin B12 deficiencies rather than a direct pathogenic factor, underlining the need for integrated biomarker-based and nutritional approaches to improve patient outcomes. CLINICAL TRIAL NUMBER: Not applicable.