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Positive metacognitions about alcohol mediate the relationship between FKBP5 variability and problematic drinking in a sample of young women.

ABSTRACT: Background:Previous research has shown that polymorphisms in the FKBP5 gene are related to some psychiatric conditions, including alcohol dependence. These relationships are moderated by the level of adverse childhood experiences that one has undergone. Maladaptive metacognition, associated with symptoms of psychiatric disorders and disturbed emotional self-regulation, is also a strong predictor of problematic alcohol use. Recent studies suggest that maladaptive metacognitions may be part of the developmental pathway from childhood abuse to drinking problems. This study attempted to identify relationships between FKBP5 polymorphisms and metacognitions about the positive effects of alcohol use and problematic drinking in a group differing in levels of childhood trauma. Methods:The sample studied was composed of 502 female participants aged 18-25 years (M=21.78; SD=1.84). Positive metacognitions about alcohol use were measured with the Positive Alcohol Metacognitions Scale (PAMS) and problematic drinking was gauged using the WHO Alcohol Use Disorders Identification Test. Levels of childhood adverse experiences were determined with the use of the Childhood Questionnaire. A total of 18 single-nucleotide polymorphisms (SNPs) in the FKBP5 gene were genotyped. Results:We did not find any interaction between the gene and childhood trauma on problematic drinking or metacognitions. However we identified a strong main effect of two SNPs of the FKBP5 gene - rs755658 and rs1334894 - on the PAMS subscale measuring positive metacognitive beliefs about emotional self-regulation. We also found nominally significant relations of several other SNPs with metacognitions and problematic drinking. Additionally, we showed that positive alcohol metacognitions mediate the relationship between problematic drinking and both rs755658 and rs1334894. Conclusion:Our results may shed some light on the biological underpinnings of the developmental pathway leading to problematic drinking through maladaptive metacognitions.

SUBMITTER: Dragan WL

PROVIDER: S-EPMC6187977 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Positive metacognitions about alcohol mediate the relationship between <i>FKBP5</i> variability and problematic drinking in a sample of young women.

Dragan Wojciech Łukasz WŁ Domozych Wojciech W Czerski Piotr M PM Dragan Małgorzata M

Neuropsychiatric disease and treatment 20181011

<h4>Background</h4>Previous research has shown that polymorphisms in the <i>FKBP5</i> gene are related to some psychiatric conditions, including alcohol dependence. These relationships are moderated by the level of adverse childhood experiences that one has undergone. Maladaptive metacognition, associated with symptoms of psychiatric disorders and disturbed emotional self-regulation, is also a strong predictor of problematic alcohol use. Recent studies suggest that maladaptive metacognitions may ...[more]

PMID: 30349266

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Project description:BACKGROUND:Genomewide association studies (GWAS) have begun to identify loci related to alcohol consumption, but little is known about whether this genetic propensity overlaps with specific indices of problem drinking in ascertained samples. METHODS:In 6,731 European Americans who had been exposed to alcohol, we examined whether polygenic risk scores (PRS) from a GWAS of weekly alcohol consumption in the UK Biobank predicted variance in 6 alcohol-related phenotypes: alcohol use, maximum drinks within 24 hours (MAXD), total score on the Self-Rating of the Effects of Ethanol Questionnaire (SRE-T), DSM-IV alcohol dependence (DSM4AD), DSM-5 alcohol use disorder symptom counts (DSM5AUDSX), and reduction/cessation of problematic drinking. We also examined the extent to which an single nucleotide polymorphism (rs1229984) in ADH1B, which is strongly associated with both alcohol consumption and dependence, contributed to the polygenic association with these phenotypes and whether PRS interacted with sex, age, or family history of alcoholism to predict alcohol-related outcomes. We performed mixed-effect regression analyses, with family membership and recruitment site included as random effects, as well as survival modeling of age of onset of DSM4AD. RESULTS:PRS for alcohol consumption significantly predicted variance in 5 of the 6 outcomes: alcohol use (?marginal R2 = 1.39%, ? area under the curve [AUC] = 0.011), DSM4AD (?marginal R2 = 0.56%; ?AUC = 0.003), DSM5AUDSX (?marginal R2 = 0.49%), MAXD (?marginal R2 = 0.31%), and SRE-T (?marginal R2 = 0.22%). PRS were also associated with onset of DSM4AD (hazard ratio = 1.11, p = 2.08e-5). The inclusion of rs1229984 attenuated the effects of the alcohol consumption PRS, particularly for DSM4AD and DSM5AUDSX, but the PRS continued to exert an independent effect for all 5 alcohol measures (?marginal R2 after controlling for ADH1B = 0.14 to 1.22%). Interactions between PRS and sex, age, or family history were nonsignificant. CONCLUSIONS:Genetic propensity for typical alcohol consumption was associated with alcohol use and was also associated with 4 of the additional 5 outcomes, though the variance explained in this sample was modest. Future GWAS that focus on the multifaceted nature of AUD, which goes beyond consumption, might reveal additional information regarding the polygenic underpinnings of problem drinking.

Dataset Information

Positive metacognitions about alcohol mediate the relationship between FKBP5 variability and problematic drinking in a sample of young women.

Publications

Positive metacognitions about alcohol mediate the relationship between <i>FKBP5</i> variability and problematic drinking in a sample of young women.

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