Tetrahydrobiopterin deficiency in schizophrenia as a new target for personalized medicine

Summary. Tetrahydrobiopterin (BH4) is an important cofactor, that involved in the synthesis of dopamine, norepinephrine, and serotonin, as well as affecting the production of nitric oxide (NO) and regulating the activity of the glutamatergic system. A few foreign studies have shown, that patients with schizophrenia had a markedly reduced level of BH4 compared to the healthy population.

The aim of this work was to study the association of BH4 deficiency with the risk of schizophrenia among Russian patients by comparison with a group of healthy volunteers.

Materials and methods: 50 patients with schizophrenia and 36 healthy volunteers
were randomly selected and underwent a biochemical study of the BH4 level using the method of competitive enzyme immunoassay (ELISA) on a spectrophotometer (Sunrise, Tecan) with a set of CEG421Ge (CloudClone Corp).

Results: it was found that the BH4 level was significantly lower in patients than in the control
group (3684.75 [1283.00; 4815.00] versus 4260.60 [4057.40; 5236.85] pmol / l, respectively, p = 0 , 0016). The proportion of patients with a BH4 level below the lower limit of the interquartile range in healthy volunteers (4057.40 pmol / l) is 30/50 (60%), the proportion of healthy volunteers with a BH4 level below this border is 9/36 (25%), the difference is statistically significant, χ2 = 10.35; p = 0.002; OR = 4.5; 95% CI [1.75; 11.56](CI — confidence interval). The correlation of BH4 level with the duration of the disease, gender, age of the subjects is very weak and not statistically significant.

Conclusion: further interdisciplinary studies are required to identify the causes and molecular mechanisms for the development of BH4 deficiency in schizophrenia and to develop approaches to personalized pharmacological intervention.

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