Aspectos sociodemográficos e a relação entre os polimorfismos da IL-10 (-819 C>T), TNFA (-308 G>A), ENOS (-786 T>C) com transtornos mentais em usuários de cocaína/crack e crack do agreste alagoano

Abstract

According to the World Drug Report, an estimated 35 million people suffer from drug use disorders. In this context, the use of cocaine stands out. Inflammation is implicated in cocaine use and associated problems, including depression and cognitive impairment. The consequences arising from the use of cocaine generate a range of physiological changes, and the role of immune system molecules in the pathophysiology of the development of comorbidities in cocaine/crack users has been identified. Thus, we aimed to investigate the relationship of polymorphisms in genes IL-10 (-819 C>T), TNFA (-308 G>A) and ENOS (-786 T>C) with mental disorders in cocaine/crack users. A cross-sectional study was carried out that included 110 users of cocaine/crack and 115 people who had never used cocaine/crack. SNPs in IL-10 (-819 C>T), TNFA (-308 G>A) and ENOS (-786 T>C) genes were genotyped by qPCR. For statistical analysis, the IBM SPSS version 22.0 software was used. As for the individuals included in this study, with a mean age of 31.4 years (±8.59), most were male, single, brown, living in urban areas, with incomplete primary education and evangelicals. Regarding the most frequent mental disorders, we identified that current major depressive episode (61.6%), current alcohol dependence (56.3%), current alcohol abuse (75%), current generalized anxiety disorder (44.6 %) and antisocial personality disorder (46.4%) were the most prevalent. The risk of suicide (49.1%) in the investigated sample was also tracked. We identified that the T allele of the IL-10 SNP (-819 C>T) was associated with a decreased risk of developing panic disorder (OR=0.44; CI=0.23 – 0.85; p=0 .01), while the C allele was correlated with increased risk for alcohol dependence (OR=1.97; CI=1.00 – 3.88, p=0.04), alcohol abuse (OR=1 .81; CI=1.02 – 3.22; p=0.04) and current psychotic syndrome (OR=2.23; CI=1.21 – 4.12; p=0.01). Furthermore, the physical aggressiveness domain was negatively correlated with the C allele (p=0.04). The CC genotype was correlated with increased odds of developing current psychotic syndrome in the codominant (OR=4.23; CI=1.29 – 13.82; p=0.01) and dominant (OR=3.07; CI=1) model .32 – 7.14; p=0.009). The G/A genotype of the TNFA (-308 G>A) SNP in the codominant model (RC=0.24; CI=0.06 – 0.87; p=0.03) was associated with reduced risk for dysthymia disorder and hypomania episode (OR=0.18; CI=0.05 – 0.64; p=0.008). Impulsiveness scores for non-planning were negatively related to the GA genotype (p=0.04). The G/A genotype was positively related to physical aggressiveness (p=0.01) and verbal aggressiveness (p=0.03). The A allele was associated with reduced risk for dysthymia disorder (OR=0.30; CI=0.09 – 0.93; p=0.03), hypomania episode (OR=0.24; CI=0.08 – 0.72; p=0.01). The A allele (p=0.02) was positively correlated with physical aggressiveness. The ENOS C/C genotype (-786 T>C) SNP was negatively related to total impulsivity scores and the T allele positively predicts verbal aggressiveness traits (p=0.04). Our results suggest that genetic polymorphisms may affect susceptibility or promote protection for clinical phenotypes of psychiatric comorbidities in cocaine and crack users and may be considered good prognostic markers.