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Associations of NLRP3 and CARD8 gene polymorphisms with alcohol dependence and commonly related psychiatric disorders: a preliminary study.

ABSTRACT: We investigated two functional polymorphisms in NLRP3 inflammasome genes (NLRP3 rs35829419 and CARD8 rs2043211) and their association with alcohol dependence and related anxiety, depression, obsession-compulsion, or aggression in 88 hospitalised alcohol-dependent patients, 99 abstinent alcohol-dependent participants, and 94 controls, all male Caucasian. Alcohol dependence-related psychiatric disorders were assessed with the Zung Depression and Anxiety scale, Buss-Durkee Hostility Inventory, Alcohol Use Disorders Identification Test, Brief Social Phobia Scale, Obsessive Compulsive Drinking Scale, and Yale-Brown Obsessive-Compulsive Scale. For genotyping we used the allele-specific quantitative polymerase chain reaction-based methods. The three groups differed significantly in CARD8 rs2043211 distribution (P=0.049; chi-squared=9.557; df=4). The NLPR3 rs35829419 polymorphism was not significantly associated with alcohol dependence. In hospitalised alcohol-dependent patients the investigated polymorphisms were not associated with scores indicating alcohol consumption or comorbid symptoms. In abstinent alcohol-dependent subjects homozygotes for the polymorphic CARD8 allele presented with the highest scores on the Zung Anxiety Scale (p=0.048; df=2; F=3.140). Among controls, CARD8 genotype was associated with high scores on the Obsessive Compulsive Drinking Scale (P=0.027; df=2; F=3.744). In conclusion, our results reveal that CARD8 rs2043211 may play some role in susceptibility to alcohol dependence, expression of anxiety symptoms in abstinent alcohol-dependent subjects, and in obsessive compulsive drinking in healthy controls. However, further studies with larger cohorts are required to confirm these preliminary findings.

SUBMITTER: Iljes AP

PROVIDER: S-EPMC8576752 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundUnhealthy alcohol use frequently co-occurs with psychiatric disorders; however, little is known about the relationship between psychiatric disorders and alcohol consumption levels. Understanding varying levels of unhealthy alcohol use among individuals with a variety of psychiatric disorders in primary care would provide valuable insight for tailoring interventions.MethodsWe conducted a cross-sectional study of 2,720,231 adult primary care patients screened for unhealthy alcohol use between 2014 and 2017 at Kaiser Permanente Northern California, using electronic health record data. Alcohol consumption level was classified as no reported use, low-risk use, and unhealthy use, per National Institute on Alcohol Abuse and Alcoholism guidelines. Unhealthy use was further differentiated into mutually exclusive groups: exceeding only daily limits, exceeding only weekly limits, or exceeding both daily and weekly limits. Multivariable multinomial logistic regression models were fit to examine associations between 8 past-year psychiatric disorders (depression, bipolar disorder, anxiety disorder, obsessive-compulsive disorder, schizophrenia, schizoaffective disorder, anorexia nervosa, and bulimia nervosa) and alcohol consumption levels, adjusting for sociodemographic and health characteristics.ResultsIn the full sample [53% female, 48% White, mean (SD) age = 46 (18) years], patients with psychiatric disorders (except eating disorders), compared to those without, had lower odds of reporting low-risk and unhealthy alcohol use relative to no use. Among patients who reported any alcohol use (n = 861,427), patients with depression and anxiety disorder, compared to those without, had higher odds of exceeding only weekly limits and both limits; patients with bulimia nervosa were also more likely to exceed both limits.ConclusionsFindings suggest that patients with anxiety disorder, depression, and bulimia nervosa who drink alcohol are more likely to exceed recommended limits, increasing risk of developing more serious problems. Health systems and clinicians may wish to consider implementing more robust screening, assessment, and intervention approaches to support these vulnerable subgroups in limiting their drinking.

Project description:ObjectiveThe authors examined psychiatric comorbidities associated with alcohol use disorders and tobacco use disorders among heterosexual, bisexual, and gay and lesbian men and women in the United States and whether stress-related factors were predictive of comorbidities.MethodsThe authors used data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (2012-2013, N=36,309) to examine the co-occurrence of past-year alcohol or tobacco use disorder with past-year anxiety disorders, mood disorders, and posttraumatic stress disorder by sexual identity (heterosexual, bisexual, gay or lesbian) and sex. The authors also examined the association of stress-related factors and social support with the presence of comorbidities.ResultsComorbidities were more prevalent among women and sexual minorities, particularly bisexual women. More than half of bisexual (55%) and gay or lesbian (51%) individuals who met criteria for a past-year alcohol use disorder had a psychiatric comorbidity, while only one-third of heterosexual individuals who met criteria for a past-year alcohol use disorder did. Similar differences were found among those who met criteria for a past-year tobacco use disorder. Among sexual minorities, the frequency of sexual orientation discrimination (adjusted odds ratio range=1.08-1.10), number of stressful life events (adjusted odds ratio range=1.25-1.43), and number of adverse childhood experiences (adjusted odds ratio range=1.04-1.18) were significantly associated with greater odds of comorbidities. Greater social support was significantly inversely associated with tobacco use disorder comorbidities (adjusted odds ratio range=0.96-0.97).ConclusionsThis research suggests that integrated substance use and mental health prevention and treatment programs are needed, particularly for individuals who identify as sexual minorities. The increased stressors experienced by sexual minority individuals may be important drivers of these high levels of comorbidities.

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Associations of NLRP3 and CARD8 gene polymorphisms with alcohol dependence and commonly related psychiatric disorders: a preliminary study.

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