ArticleMolecular psychiatry2018
EFhd2/Swiprosin-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Self-management with alcohol over lifespan: psychological mechanisms, neurobiological underpinnings, and risk assessment.Molecular psychiatry · 2023Pooled it
- The IMAGEN study: a decade of imaging genetics in adolescents.Molecular psychiatry · 2020Pooled it
- Investigating the role of EFhd2 protein in modulating tau pathology in a tauopathy mouse model.Frontiers in molecular neuroscience · 2026Article
- Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models.Psychopharmacology · 2023Article
- Analysis of hyperforin (St. John's wort) action at TRPC6 channel leads to the development of a new class of antidepressant drugs.Molecular psychiatry · 2022Article
- EFhd2 brain interactome reveals its association with different cellular and molecular processes.Journal of neurochemistry · 2021Article
- Alcohol and the brain: from genes to circuits.Trends in neurosciences · 2021Review
- Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects.Molecular psychiatry · 2021Article
- Single-step genome-wide association study for social genetic effects and direct genetic effects on growth in Landrace pigs.Scientific reports · 2020Article
- Matrix Metalloproteinase-9 Overexpression Regulates Hippocampal Synaptic Plasticity and Decreases Alcohol Consumption and Preference in Mice.Neurochemical research · 2020Article
- EFHD2 contributes to non-small cell lung cancer cisplatin resistance by the activation of NOX4-ROS-ABCC1 axis.Redox biology · 2020Article
- Association betweenThe Journal of international medical research · 2020Article
- Non-pharmacological factors that determine drug use and addiction.Neuroscience and biobehavioral reviews · 2020Review
- The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Enhanced Alcohol Preference and Anxiolytic Alcohol Effects in Niemann-Pick Disease Model in Mice.Frontiers in neurology · 2019Article
- CRISPR/Cas9, the Powerful New Genome-Editing Tool for Putative Therapeutics in Obesity.Journal of molecular neuroscience : MN · 2018Review
- Article
- Ulk4 regulates GABAergic signaling and anxiety-related behavior.Translational psychiatry · 2018Article
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Authors and funding
46 authors at 14 institutions in 6 countries.
Funding
Abstract
In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with β-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.
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Registered trials
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