ABSTRACT
It was reported that the levels of tetrahydrobiopterin (BH4) are reduced in schizophrenia. However, mechanisms of BH4 deficiency in schizophrenia had not been studied precisely. OBJECTIVE: the search of the association between BH4 deficiency in schizophrenia and a range of biochemical and clinical parameters for the evaluation of the possible mechanisms of BH4 loss and its role in the development of the symptoms. METHODS: 93 patients with schizophrenia and 60 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, cobalamin (B12), homocysteine, C-reactive protein (CRP), reduced glutathione (GSH) levels in the blood serum.Patients underwent standardized psychopathological examination. RESULTS: In patients, the levels of BH4 and folate were lower (p = 0.001 and p = 0.054, respectively), and the levels of homocysteine were higher (p = 0.012) compared to the control group. BH4 levels directly moderately correlated with folate (ρ = 0.43; p = 0.0029) and B12 levels (ρ = 0.43; p = 0.0020) and inversely moderately correlated with homocysteine levels (ρ = -0.54; p = 0.00015) in patients. Cluster analysis identified schizophrenia biotype characterized by a deficiency of BH4, folate, B12, and hyperhomocysteinemia. The clinical characteristics of this biotype were not specific. CRP and GSH were higher in patients compared to controls, but their association with serum BH4 was not confirmed.
Subject(s)
Phenylketonurias , Schizophrenia , C-Reactive Protein , Case-Control Studies , Folic Acid , Homocysteine , Humans , Vitamin B 12ABSTRACT
BACKGROUND: Currently, oxidative stress as part of the pathogenesis of schizophrenia attracts much attention. In this regard, it becomes relevant to assess the level of redox imbalance in patients with schizophrenia, its impact on existing symptoms and the possibility of its treatment. The antioxidant N-acetylcysteine is one of the potential drugs that affects oxidative stress. OBJECTIVE: To study the possibilities of the use of N-acetylcysteine in patients with schizophrenia. MATERIAL AND METHODS: The study included 20 patients diagnosed with paranoid schizophrenia with the disease duration of less than 3 years, randomly assigned to the main group (taking N-acetylcysteine at a dose of 2000 mg per day for 60 days) and a comparison group (placebo) in a double-blinded manner. At the beginning and end of the study, cognitive functions were evaluated using the specialized instrument BACS, the severity of psychopathological symptoms was evaluated using PANSS, and blood was collected to determine the level of glutathione (GSH), which is a metabolite of N-acetylcysteine. RESULTS: There was a significant decrease in positive PANSS score (p=0.013), negative PANSS score (p=0.002) and the general pathology PANSS score (p=0.004) in the main group. Compared with the comparison group, the dynamics of the negative PANSS score (p=0.005) and the general psychopathology PANSS score (p=0.004) was significantly different. When assessing the dynamics of cognitive functions in the main group, a significant improvement in indicators was established in the task for a sequence of numbers that characterizes working memory (p=0.037). The level of GSH significantly increased in the main group (p=0.01), however, there were no statistically significant differences between groups at the final visit. CONCLUSION: N-acetylcysteine has a positive effect on the negative, general psychopathology PANSS scores, some cognitive functions, in particular, working memory, that allows considering this drug as a promising method of augmentation of schizophrenia therapy and requires further attentive study.
