CNR1 Gene and Risk of the Metabolic Syndrome in Patients With Schizophrenia

Abstract

Metabolic disturbances are more prevalent in patients with schizophrenia (SCZ) than in the general population. The endocannabinoid system plays an important role in the regulation of dopamine transmission and several metabolic pathways, and the endocannabinoid receptor type 1 gene (CNR1) is considered a candidate gene for both SCZ and metabolic disorders. We examined whether genetic variation in CNR1 was associated with metabolic syndrome (MetS) in a naturalistic cohort of 407 patients with SCZ. The minor alleles of rs6928499, rs1535255, and rs2023239 were nominally associated with a lower risk of MetS [odds ratio (OR), 0.56; 95% confidence interval (CI), 0.37-0.84; P = 0.006; OR, 0.56; 95% CI, 0.37-0.84; P = 0.006; and OR, 0.44; 95% CI, 0.27-0.72; P = 0.001, respectively, adjusted for age, sex, duration of illness, clozapine or olanzapine treatment). These differences were mainly due to differences in high-density lipoprotein cholesterol and fasting glucose but not in body mass index or waist circumference. No significant association of the other polymorphisms (rs806377, rs1049353, rs6454674, and rs806379) with MetS was found. These results provide evidence that the prevalence of MetS is associated with the CNR1 gene in patients with SCZ during long-term treatment with antipsychotic treatment. Further studies are needed to uncover the exact molecular basis for this association, which could provide novel treatment targets for the MetS.

Prevalence of polymorphisms in the ANKK1, DRD2, DRD3 genes and metabolic syndrome in refractory schizophrenia

“…The imbalance of this marker is an indicator of risk for chronic-degenerative diseases and increased mortality. Routine follow-up on a regular basis and education on healthy lifestyle are necessary to minimize the risks of complications 2 - 15 . The hypotheses raised in this study suggest that the health care for refractory schizophrenic patients using clozapine must be comprehensive, and the planning of strategies aimed at minimizing the risk of metabolic alterations should be one of the main goals of the individual therapeutic plan for these patients 2 - 14 .…”

“…According to Papanastasiou (2013), women tend to have increased rates of MS compared to men, a datum corroborated in the present study. However, that data must be carefully interpreted; men are likely to be at increased risk of developing cardiovascular disease as the possible result of a combination of unhealthy lifestyles and lack of health care when compared to women 15 - 16 .…”

Bridging the Gap between Genes and Language Deficits in Schizophrenia: An Oscillopathic Approach

“…Translational convergent functional genomics studies have highlighted CNR1 as an important gene for schizophrenia onset (Ayalew et al, 2012). Several risk polymorphisms of the gene have been related to the disease, and specifically, to brain changes and metabolic disturbances in schizophrenics (Yu et al, 2013; Suárez-Pinilla et al, 2015). Interestingly, CNR1 has also been linked to cases of complete absence of expressive speech (Poot et al, 2009).…”

Brain structural and clinical changes after first episode psychosis: Focus on cannabinoid receptor 1 polymorphisms

“…Nevertheless, other studies have shown that CNR1 variants are associated with depression remission after only 12 weeks (Mitjans et al, 2013). Previous association studies which have investigated CNR1 rs2023239 polymorphisms have tested the relationship of these variants to cannabis withdrawal (Haughey et al, 2008), impulsivity (Ehlers et al, 2007) and metabolic syndrome in patients with schizophrenia (Yu et al, 2013) as well as in the general population (Milewicz et al, 2011;Lenarcik-Kabza et al, 2014). On the other hand, the significant interaction in patients homozygous for the G allele in rs1049353, the at-risk allele T for rs1535255 and the T/C for rs20233239 polymorphism yielded significantly higher SAPS scores after 3 years compared with SAPS scores in the other patients.…”

“…For example, the minor alleles of rs1535255 and rs2023239 were associated with lower risk of metabolic syndrome in schizophrenia (Yu et al, 2013). However, other authors found no significant association between CNR1 genes and obesity (Muller et al, 2007;Zhuang et al, 2012).…”