Homocysteine in Schizophrenia: Independent Pathogenetic Factor with Prooxidant Activity or Integral Marker of Other Biochemical Disturbances?

Autor: Zhilyaeva TV; Privolzhsky Research Medical University, Russia., Piatoikina AS; Nizhny Novgorod Clinical Psychiatric Hospital No. 1, Russia., Bavrina AP; Privolzhsky Research Medical University, Russia., Kostina OV; Privolzhsky Research Medical University, Russia., Zhukova ES; Nizhny Novgorod Research Institute for Hygiene and Occupational Pathology, Russia., Shcherbatyuk TG; Nizhny Novgorod Research Institute for Hygiene and Occupational Pathology, Russia.; Pushchino State Institute of Natural Science, Russia.; Moscow Region State University, Russia., Blagonravova AS; Privolzhsky Research Medical University, Russia., Dubinina EE; V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology, Russia., Mazo GE; V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology, Russia.
Jazyk: angličtina
Zdroj: Schizophrenia research and treatment [Schizophr Res Treatment] 2021 Oct 13; Vol. 2021, pp. 7721760. Date of Electronic Publication: 2021 Oct 13 (Print Publication: 2021).
DOI: 10.1155/2021/7721760
Abstrakt: A wide range of studies have demonstrated that hyperhomocysteinemia is associated with the risk of schizophrenia, but currently available assumptions about the direct involvement of homocysteine (Hcy) in the pathogenesis of schizophrenia are hypothetical. It is possible that in vivo Hcy is only a marker of folate metabolism disturbances (which are involved in methylation processes) and is not a pathogenetic factor per se. Only one study has been conducted in which associations of hyperhomocysteinemia with oxidative stress in schizophrenia (oxidative damage to protein and lipids) have been found, and it has been suggested that the oxidative stress may be induced by the elevated Hcy in schizophrenic patients. But the authors did not study the level of reduced glutathione (GSH), as well as possible causes of hyperhomocysteinemia-disturbances of folate metabolism. The aim of this work is to analyze the association of Hcy levels with the following: (1) redox markers in schizophrenia GSH, markers of oxidative damage of proteins and lipids, and the activity of antioxidant enzymes in blood serum; (2) with the level of folate and cobalamin (В12); and (3) with clinical features of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). 50 patients with schizophrenia and 36 healthy volunteers, matched by sex and age, were examined. Hcy in patients is higher than in healthy subjects ( p = 0.0041), and this may be due to the lower folate level in patients ( p = 0.0072). In patients, negative correlation was found between the level of Hcy both with the level of folate ( ρ = -0.38, p = 0.0063) and with the level of B12 ( ρ = -0.36, p = 0.0082). At the same time, patients showed higher levels of oxidative modification of serum proteins ( p = 0.00046) and lower catalase (CAT) activity ( p = 0.014). However, Hcy is not associated with the studied markers of oxidative stress in patients. In the group of patients with an increased level of Hcy (>10  μ mol/l, n = 42) compared with other patients ( n = 8), some negative symptoms (PANSS) were statistically significantly more pronounced: difficulty in abstract thinking (N5, p = 0.019), lack of spontaneity and flow in conversation (N6, p = 0.022), stereotyped thinking (N7, p = 0.013), and motor retardation (G7, p = 0.050). Thus, in patients with schizophrenia, hyperhomocysteinemia caused by deficiency of folate and B12 is confirmed and can be considered a marker of disturbances of vitamin metabolism. The redox imbalance is probably not directly related to hyperhomocysteinemia and is hypothetically caused by other pathological processes or by an indirect effect of Hcy, for example, on the enzymatic antioxidant defence system (CAT activity), which requires further exploration. Further study of the role of Hcy in the pathogenesis of schizophrenia is relevant, since the proportion of patients with hyperhomocysteinemia is high and correlations of its level with negative symptoms of schizophrenia are noted.
Competing Interests: The authors declare that they have no conflicts of interest.
(Copyright © 2021 T. V. Zhilyaeva et al.)
Databáze: MEDLINE
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