ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
FKBP5 moderates alcohol withdrawal severity: human genetic association and functional validation in knockout mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 61 citations in OpenAlex.
- Article
- Inhibition of FKBP51 alleviates depressive-like behaviors via AKT/mTOR-dependent autophagy and synaptic plasticity.The international journal of neuropsychopharmacology · 2026Article
- Epigenetic and Transcriptomic Impacts of Ethanol Vary by Brain Region and Extent of Exposure.eNeuro · 2026Article
- Central amygdalaNeurobiology of stress · 2026Article
- The influence of stress and social defeat on neurobiological reinforcement mechanisms across reward to withdrawal in nicotine addiction.Psychopharmacology · 2025Review
- CircRNA hypomethylation in the human amygdala implicatesbioRxiv : the preprint server for biology · 2025Article
- Chemogenetic inhibition of central amygdala CRF-expressing neurons decreases alcohol intake but not trauma-related behaviors in a rat model of post-traumatic stress and alcohol use disorder.Molecular psychiatry · 2024Article
- The effects of BDNF rs6265 and FGF21 rs11665896 polymorphisms on alcohol use disorder-related impulsivity in Han Chinese adults.Frontiers in psychiatry · 2024Article
- Exploring core symptoms of alcohol withdrawal syndrome in alcohol use disorder patients: a network analysis approach.Frontiers in psychiatry · 2024Article
- Chronic alcohol-induced long-lasting working memory deficits are associated with altered histone H3K9 dimethylation in the prefrontal cortex.Frontiers in behavioral neuroscience · 2024Article
- Article
- FKBP5 inhibitors modulate alcohol drinking and trauma-related behaviors in a model of comorbid post-traumatic stress and alcohol use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Polygenic influences on the behavioral effects of alcohol withdrawal in a mixed-ancestry population from the collaborative study on the genetics of alcoholism (COGA).Molecular and cellular neurosciences · 2023Article
- Analysis of the Selective Antagonist SAFit2 as a Chemical Probe for the FK506-Binding Protein 51.ACS pharmacology & translational science · 2023Review
- Alcohol-specific transcriptional dynamics of memory reconsolidation and relapse.Translational psychiatry · 2023Article
- Methylation of genes and regulation of inflammatory processes on emotional response in young adults with alcoholic parents.Brain, behavior, & immunity - health · 2022Article
- Epigenome-wide association analyses of active injection drug use.Drug and alcohol dependence · 2022Article
- FKBP51 modulates hippocampal size and function in post-translational regulation of Parkin.Cellular and molecular life sciences : CMLS · 2022Article
- Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice.Frontiers in psychiatry · 2022Article
- Genetic association of FKBP5 with trait resilience in Korean male patients with alcohol use disorder.Scientific reports · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Alcohol withdrawal is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction. The FKBP5 gene codes for a co-chaperone, FK506-binding protein 5, that exerts negative feedback on HPA axis function. This study aimed to examine the effects of single-nucleotide polymorphisms (SNPs) of the FKBP5 gene in humans and the effect of Fkbp5 gene deletion in mice on alcohol withdrawal severity. We genotyped six FKBP5 SNPs (rs3800373, rs9296158, rs3777747, rs9380524, rs1360780, and rs9470080) in 399 alcohol-dependent inpatients with alcohol consumption 48 h before admission and recorded scores from the Clinical Institute Withdrawal Assessment-Alcohol revised (CIWA-Ar). Fkbp5 gene knockout (KO) and wild-type (WT) mice were assessed for alcohol withdrawal using handling-induced convulsions (HICs) following both acute and chronic alcohol exposure. We found the minor alleles of rs3800373 (G), rs9296158 (A), rs1360780 (T), and rs9470080 (T) were significantly associated with lower CIWA-Ar scores whereas the minor alleles of rs3777747 (G) and rs9380524 (A) were associated with higher scores. The haplotype-based analyses also showed an association with alcohol withdrawal severity. Fkbp5 KO mice showed significantly greater HICs during withdrawal from chronic alcohol exposure compared with WT controls. This study is the first to show a genetic effect of FKBP5 on the severity of alcohol withdrawal syndrome. In mice, the absence of the Fkbp5 gene enhances sensitivity to alcohol withdrawal. We suggest that FKBP5 variants may trigger different adaptive changes in HPA axis regulation during alcohol withdrawal with concomitant effects on withdrawal severity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.