Association of the PPAR-γ Gene with Altered Glucose Levels and Psychosis Profile in Schizophrenia Patients Exposed to Antipsychotics

Abstract

ObjectiveMetabolic abnormalities, e.g., diabetes, are common among schizophrenia patients. Peroxisome proliferator activated receptor-γ (PPAR-γ) regulates glucose/lipid metabolisms, and schizophrenia like syndrome may be induced by actions involving retinoid X receptor-α/PPAR-γ heterodimers. We examined a possible role of the PPAR-γ gene in metabolic traits and psychosis profile in schizophrenia patients exposed to antipsychotics.MethodsSingle nucleotide polymorphisms (SNPs) of the PPAR-γ gene and a serial of metabolic traits were determined in 394 schizophrenia patients, among which 372 were rated with Positive and Negative Syndrome Scale (PANSS).ResultsSNP-10, -12, -18, -19, -20 and -26 were associated with glycated hemoglobin (HbA1c) whereas SNP-18, -19, -20 and -26 were associated with fasting plasma glucose (FPG). While SNP-23 was associated with triglycerides, no associations were identified between the other SNPs and lipids. Further haplotype analysis demonstrated an association between the PPAR-γ gene and psychosis profile.ConclusionOur study suggests a role of the PPAR-γ gene in altered glucose levels and psychosis profile in schizophrenia patients exposed to antipsychotics. Although the Pro12Ala at exon B has been concerned an essential variant in the development of obesity, the lack of association of the variant with metabolic traits in this study should not be treated as impossibility or a proof of error because other factors, e.g., genes regulated by PPAR-γ, may have complicated the development of metabolic abnormalities. Whether the PPAR-γ gene modifies the risk of metabolic abnormalities or psychosis, or causes metabolic abnormalities that lead to psychosis, remains to be examined.

Serum peroxisome proliferator-activated receptor-gamma levels in acute phase of male patients with schizophrenia and their relationship with metabolic parameters

“…In the literature, it was reported that the weight gain in schizophrenia patients who are using atypical antipsychotics was related to PPARγ gene polymorphism [18] and the glucose-level changes in patients who were administered antipsychotics may have been related to PPARγ gene [19]. Although PPARγ activity was shown to have a role in glucose and lipid metabolisms and Type 2 diabetes, we did not find a relationship between serum PPARγ level and MetS parameters.…”

Plasma levels of antipsychotics and the severity of side-effects in the treatment of schizophrenia exacerbation

“…По-видимому, возникновение данного ПЭ в значительной степени свя-зано с индивидуальными особенностями пациентов, в том числе генетическими [38]. Данные литературы [39,40] позволяют предполагать некоторую связь между повыше-нием уровня глюкозы крови и особенностями концентра-ции оланзапина и клозапина, но небольшое число паци-ентов, получавших клозапин в нашей выборке, не позво-ляет оценить достоверность указанной связи в рамках представленного исследования.…”

Validation of Brain Angiotensin System Blockade as a Novel Drug Target in Pharmacological Treatment of Neuropsychiatric Disorders

“…However, PPAR-γ activation does not provide symptomatic improvement in psychotic patients [195]. Whether it modifies the risk of metabolic abnormalities is yet to be found [196,197]. Interestingly, therapeutic advances in the treatment of addiction also focused on nuclear receptors.…”