Dataset Information

Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans.

ABSTRACT: Alcohol misuse has been linked to dysregulation of stress, emotion, and reward brain circuitries. A candidate key mediator of this association is the FK506-binding protein (FKBP5), a negative regulator of the glucocorticoid receptor. The aim of the present study was to further understand the Fkbp5/FKBP5-related genetic underpinnings underlying the relationship between early life social relations and alcohol drinking. The effect of maternal separation and voluntary alcohol drinking on Fkbp5 expression was investigated in the brain of young adult rats, whereas the interaction effect of the functional FKBP5 single nucleotide polymorphism rs1360780 genotype and parent-child relationship on problematic drinking was examined in young adult humans. In rats, Fkbp5 expression in the nucleus accumbens and ventral tegmental area, core regions of the reward system, was affected in a region-dependent manner and in opposite direction by maternal separation and alcohol drinking. Fkbp5 expression in the cingulate cortex was affected by the combined effect of maternal separation and alcohol drinking. In humans, the TT genotype, in the presence of a poor relationship between the child and parents, was associated with problematic drinking behavior. The present findings suggest that Fkbp5 expression in mesocorticolimbic dopaminergic regions associates with early life stress-mediated sensitivity to alcohol drinking and that FKBP5 genotype interacts with parent-child relationship to influence alcohol drinking. These findings are the first to point to a role of FKBP5 in propensity to alcohol misuse and call for studies of the underlying molecular mechanisms to identify potential drug targets.

SUBMITTER: Nylander I

PROVIDER: S-EPMC5583263 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans.

Nylander Ingrid I Todkar Aniruddha A Granholm Linnea L Vrettou Maria M Bendre Megha M Boon Wout W Andershed Henrik H Tuvblad Catherine C Nilsson Kent W KW Comasco Erika E

Molecular neurobiology 20161005 8

Alcohol misuse has been linked to dysregulation of stress, emotion, and reward brain circuitries. A candidate key mediator of this association is the FK506-binding protein (FKBP5), a negative regulator of the glucocorticoid receptor. The aim of the present study was to further understand the Fkbp5/FKBP5-related genetic underpinnings underlying the relationship between early life social relations and alcohol drinking. The effect of maternal separation and voluntary alcohol drinking on Fkbp5 expre ...[more]

PMID: 27709495

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Project description: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.

Project description:Music is a ubiquitous feature of young adults' social drinking environments, yet no studies have assessed whether and how it impacts risky decisions to drink alcohol. Previous research on the influence of music on risky decisions is largely based around decision tasks with monetary incentives.MethodsTo assess the impact of music listening on risky drinking decisions, the current study used visual alcohol cues paired with hypothetical risky drinking scenarios (e.g., "You do not have a safe ride home" for alcohol). Young adult women with a history of alcohol abuse (N = 34) and casual-drinking control women (N = 29) made hypothetical decisions about whether or not to drink alcohol, or eat food (an appetitive control condition), in risky contexts while personal "party music" (music chosen by participants for "going out") and "home music" (music chosen for "staying in") played in the background. The main dependent measure - likelihood of drinking - was reported on a 4-point scale where 1 corresponded to "very unlikely", and 4 to "very likely".ResultsListening to party music while making decisions increased the likelihood of making risky decisions, regardless of alcohol abuse history, while other personal music did not. Further, party music specifically increased the likelihood of risky drinking decisions relative to risky eating decisions. As expected, those with a history of alcohol abuse made more risky drinking decisions in general, regardless of the type of music heard.DiscussionThe results suggest that party music is an important feature of the drinking environment associated with increased risky decisions about drinking alcohol in young adult women, regardless of their history of alcohol abuse. The finding that music plays an important role in risky drinking decisions indicates that further investigation into the real-world drinking environments of young adults is crucial, as it will aid in the development of a more complete picture of risky drinking decisions in young adults.

Dataset Information

Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans.

Publications

Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans.

Similar Datasets

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