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

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 metacogni- tion, 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 metacog- nitive 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 develop- mental pathway leading to problematic drinking through maladaptive metacognitions.