Asymmetric dimethylarginine in somatically healthy schizophrenia patients treated with atypical antipsychotics: a case–control study

Abstract

BackgroundSchizophrenia is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, and the L-arginine:ADMA ratio are markers of endothelial dysfunction that predict mortality and adverse outcome in a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L-arginine: ADMA ratio are positively correlated to measures of oxidative stress.MethodsWe included 40 schizophrenia patients treated with AAP, but without somatic disease or drug abuse, and 40 healthy controls. Plasma concentrations of ADMA and L-arginine were determined by high-performance liquid chromatography. Data were related to markers of systemic oxidative stress on DNA, RNA and lipids, as well as measures of medication load, duration of disease and current symptomatology.ResultsPlasma ADMA and the L-arginine:ADMA ratio did not differ between schizophrenia patients and controls. Furthermore, ADMA and the L-arginine:ADMA ratio showed no correlations with oxidative stress markers, medication load, or Positive and Negative Syndrome Scale scores.ConclusionsSchizophrenia and treatment with AAP was not associated with increased levels of plasma ADMA or the L-arginine:ADMA ratio. Furthermore, plasma levels of ADMA were not associated with levels of systemic oxidative stress in vivo.

Comparison of serum levels of asymmetric dimethylarginine between patients who take two types of atypical anti psychotics

“…There was also a statistically significant difference between the control group compared to clozapine receiving schizophrenia patients and the no-drug group in terms of ADMA, and this is consistent with the study of Das (24), Celik (19), and Zincir (22). However, the study of Jorgensen et al (14) showed no difference between various groups.…”

“…In another study, short-term treatment initially creates a protection against endothelial damage which may be due to reduced agitation and activity of the autonomic nervous system, but no significant association was found between the disease severities (9). This study showed that drug consumption is a factor which increases possible risk factors in heart disease (14).…”

“…In many studies, it was found that higher levels of AD-MA is related to higher risks for acute coronary events (1,(8)(9)(10).…”

“…Treatment with atypical antipsychotics can increase traditional risk factors of coronary artery disease, and in many studies, clozapine and olanzapine were at the top of the list of the atypical antipsychotics (11)(12)(13)(14).…”

“…So far, investigations on the prevalence of metabolic syndrome were based on traditional cardiovascular risk factors and few studies have been performed to compare the prevalence of cardiovascular risk factors among atypical antipsychotics based on nontraditional risk factors (17,18) and there is no study on other cardiovascular biomarkers, like ADMA, in patients receiving different antipsychotics. Also, most of the previous studies consider only one factor (ADMA) in schizophrenic patients (10,18,19) or only a group of schizophrenic patients (20), and no study examined a group that discontinued their medication (21). Therefore, in this study, we compares serum levels of ADMA between patients who take two different types of atypical antipsychotics and also a healthy control group.…”