Objective: The increasing rates of metabolic syndrome and cardiovascular disease in schizophrenia led to investigation into their causes, including atypical antipsychotics and pharmacogenetic variants. This study focused on the peripheral vasculature as a cardiovascular phenotype and the influence of atypical antipsychotics, the aberrant metabolism of nitric oxide caused by endothelial nitric oxide synthetase (eNOS) genetic variants and metabolic syndrome in a cross-sectional sample of schizophrenia subjects.
Methods: Associations between eNOS genetic variants and endothelial function was assessed in a cohort of schizophrenia patients taking antipsychotic drugs, whom were undergoing a clinical assessment for endothelial function via the method of peripheral artery tonometry (RH-PAT), as well as metabolic syndrome criteria screening. Analyses were conducted on the entire cohort, then again after stratifying by metabolic syndrome, to investigate the effect of the eNOS variants and metabolic syndrome on endothelial functionality.
Results: We included 203 subjects with a mean age of 46 years. The cohort was 36% female, 36% had metabolic syndrome and 85% were currently using atypical antipsychotics. We found associations between the eNOS T⁻⁷⁸⁶C and worse endothelial functioning (lower RH-PAT values) only in schizophrenia patients without metabolic syndrome.
Conclusions: Our results suggested that when schizophrenia patients progress to meet metabolic syndrome criteria, the genetic protection of the eNOS T⁻⁷⁸⁶C variant on endothelial function is no longer seen: Other factors of this pro-inflammatory state may be overriding this effect. The results of this study need replication and the factors driving endothelial dysfunction in patients with metabolic syndrome warrant further investigation.
Keywords: Antipsychotic drugs; endothelial cells; endothelial function; inflammation; metabolic syndrome; nitric oxide synthetase; peripheral artery tonometry; pharmacogenetics; schizophrenia.