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

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 ß-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.

Pruritus: control of itch in patients undergoing dialysis.

Chronic kidney disease (CKD)-associated pruritus is a significant clinical symptom affecting more than 50% of patients on hemodialysis. Restricted by the availability of effective therapeutic options, the management of CKD-associated pruritus remains a treatment challenge. Evaluating research in this area is difficult, as most studies are not comparable due to differing methodologies and study designs, limited number of patients, and the lack of standardized measures. The most frequently used therapy is UVB phototherapy, eliciting favorable responses in most patients. Newer approaches, such as treatment with the m-opiod-receptor antagonist, naltrexone, have yielded conflicting results. The use of the k-opioid-receptor-agonist, nalfurafine, appears to be partially effective in relieving CKD-associated pruritus, as shown by a meta-analysis of 2 clinical trials. Promising results have been obtained by treatment with the anticonvulsant gabapentin. CKD-associated pruritus is thought to be mediated by a proinflammatory state, which explains why immunomodulating drugs (e.g., thalidomide, tacrolimus, and pentoxiphylline) are effective in some patients. Treatment of CKD-associated pruritus should be undertaken according to individual benefit-risk ratio assessments.