Endothelial nitric oxide synthetase genetic variants, metabolic syndrome and endothelial function in schizophrenia

• Published in: Journal of psychopharmacology (Oxford) Vol. 28; no. 4; pp. 349 - 356
• Main Authors: Burghardt, KJ, Grove, TB, Ellingrod, VL
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-04-2014; Sage Publications; Sage Publications Ltd
• Subjects: Adult; Adult and adolescent clinical studies; Antipsychotic Agents - therapeutic use; Biological and medical sciences; Cross-Sectional Studies; Disease Progression; Endothelium, Vascular - physiopathology; Female; Genetics; Humans; Male; Manometry; Medical sciences; Metabolic diseases; Metabolic syndrome; Metabolic Syndrome - etiology; Metabolic Syndrome - physiopathology; Middle Aged; Miscellaneous; Neuropharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - genetics; Other metabolic disorders; Pharmacogenetics; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Risk Factors; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - genetics; Schizophrenia - physiopathology; endothelial function; metabolic syndrome; endothelial cells; nitric oxide synthetase; Antipsychotic drugs; inflammation; schizophrenia; pharmacogenetics; peripheral artery tonometry; Endocrinopathy; Endothelial cell; Neuroleptic; Psychotropic; Pharmacotherapy; Schizophrenia; Cardiovascular disease; Metabolic syndrome; Psychosis; Genetics; Antipsychotic; Drug; Pharmacogenetics; Enzyme; Genetic variant; Metabolic diseases; Nitric-oxide synthase; Endothelium; Genetic disease; Treatment; Oxidoreductases
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881113516200

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.