Type

Journal Article

Authors

C P Müller
G Schumann
A Lourdusamy
C Alzheimer
V Eulenburg
T Bäuerle
A Schambony
M N Smolka
T Paus
F Nees
and 35 others

Subjects

Psychology

Topics
personality traits anxiety receptor agonist alcohol consumption genetic gene expression magnetic resonance imaging mri alcohol drinking

EFhd2/Swiprosin-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction. (2016)

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.Molecular Psychiatry advance online publication, 11 April 2017; doi:10.1038/mp.2017.63.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

C P Müller, G Schumann, A Lourdusamy, C Alzheimer, V Eulenburg, T Bäuerle, A Schambony, M N Smolka, T Paus, F Nees and 35 others

Experts in our system

1
Gunter Schumann
Trinity College Dublin
Total Publications: 55
 
2
Michael N Smolka
Trinity College Dublin
Total Publications: 56
 
3
Tomas Paus
Trinity College Dublin
Total Publications: 56
 
4
Frauke Nees
Trinity College Dublin
Total Publications: 53