Cumulative effect of genetic factors of folate metabolism on suicidality indicators in schizophrenia

Suicide is one of the most common causes of premature death in patients with schizophrenia. There are several prerequisites for this: some genetic risk factors for suicide are common to genetic risk factors for schizophrenia; Patients with schizophrenia are more likely than the general population to experience depression, the association of which with suicidality has been confirmed in numerous studies. Suicide is a complex multifactorial behavioral phenotype that is associated with a large number of genetic and environmental factors. Hypothetically, disorders of folate metabolism, including genetic factors affecting folate metabolism, may contribute to the development of depressive symptoms and suicidality in schizophrenia. Genetic polymorphism of the key enzyme of folate metabolism, methylenetetrahydrofolate reductase (MTHFR 677 C>T), is a risk factor for both schizophrenia and depression. At the same time, there are studies demonstrating the connection between folate deficiency and the risk of suicide and the connection of this genetic factor with the presence of a suicide attempt in schizophrenia. At the same time, a number of other genetic factors of folate metabolism, the influence of which on folate metabolism and the development of pathology has been confirmed outside the context of this topic, have not yet been studied from the point of view of their influence on suicidality in schizophrenia. The aim of this work was to study the association of combined carriage of polymorphic variants in folate metabolism genes with suicidality and depressive symptoms in schizophrenia. Materials and methods: in 119 patients with schizophrenia, the carriage of alleles in 10 polymorphic loci associated with folate metabolism was studied using real-time PCR. Patients were assessed clinically using the Columbia Suicide Risk Scale, the Positive and Negative Syndrome Scale for Schizophrenia, the Calgary Depression in Schizophrenia Scale, and the Snight-Hamilton Anhedonia Scale, blinded to laboratory results. Results: 9 out of 10 studied genetic factors were weakly associated with indicators of suicidal risk, however, the total number of polymorphic genotypes and the total allelic load for 9 out of 10 studied loci makes a statistically highly significant contribution to most indicators of suicidality. The severity of depression and the PANSS scale of productive symptoms and general psychopathology in patients is also associated with indicators of suicidal risk, but the genetic factor is not associated with clinical indicators at the time of examination. It is likely that the clinical and genetic factors studied in this work make independent contributions to suicide risk in schizophrenia. Conclusion: The total carriage of polymorphic homozygous genotypes at one-carbon metabolism loci may have a cumulative effect on suicidality rates in schizophrenia, regardless of the actual mental status, which requires replication in further studies.