Factors contributing to the escalation of alcohol consumption

The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice

“…Social anxiety is a risk factor for AUD [23, 24], and previous research demonstrated that humans carrying at least one Met66BDNF allele report higher levels of social anxiety [25]. Since male Met68BDNF mice exhibit a social anxiety phenotypes, we examined the possibility that mice carrying the mutation prefer alcohol vs. social interaction.…”

“…Male Met68BDNF mice consume alcohol excessively and compulsively [14], however, the underlying cause of this phenotype is unknown. Humans carrying the Met66BDNF allele show increased social anxiety [25], and stress and anxiety including social anxiety are thought to be major contributors to AUD [19, 23]. Thus, to determine if the mouse BDNFVal68Met polymorphism increases susceptibility for social anxiety in female and male mice, we first measured sociability and social novelty behaviors in using a three-chamber social interaction paradigm [27, 28].…”

“…For example, a global meta-analysis concluded that 27-40% of individuals with major depressive disorder experience an AUD during their lifetime, and 20-40% of people with anxiety disorders also develop an AUD [19]. One potential explanation for this phenomenon is the so-called "self-medication hypothesis", which posits that individuals consume increasing quantities of alcohol in order to elicit relief for symptoms of unrelated mood disorders [20][21][22] including social anxiety [23]. Together, these reports show that social anxiety is a risk factor for heavy alcohol use.…”

“…One potential explanation for this phenomenon is the so-called "self-medication hypothesis", which posits that individuals consume increasing quantities of alcohol in order to elicit relief from symptoms of mood disorders including social anxiety [20][21][22][23]. In fact, 10% of people suffering from AUD also endure social anxiety [23], and subjects who suffer from AUD are 4.5 times more likely to also exhibit social anxiety [24]. Heterozygous (Val/Met) and homozygous (Met/Met) genotypes have been linked with anxiety and specifically social anxiety in humans [13,25].…”

Genetic Variability of Incretin Receptors and Alcohol Dependence: A Pilot Study

“…Family, twin, and adoption studies ( Cloninger et al, 1981 ; Heath et al, 1997 ; Verhulst et al, 2015 ) and a recent meta-analysis ( Verhulst et al, 2015 ) indicated that heritability estimates are pretty high. Preclinical and clinical studies have shown that genetic variability is associated with susceptibility and development of AUD ( Hiroi and Agatsuma, 2005 ; Jones et al, 2015 ; Bowen et al, 2022 ). A genome-wide meta-analysis on AUD and problematic alcohol use, which included 435,563 subjects of European ancestry, identified 29 independent risk variants, 19 of which were novel ( Zhou et al, 2020 ).…”