The GABA type A receptor α5 subunit gene is associated with bipolar I disorder
ABSTRACT Several genetic studies have revealed that bipolar disorders are linked with the chromosomal locus of 15q11-q13, where the gamma-aminobutyric acid (GABA) receptor alpha5 subunit gene (GABRA5) locates. GABA is one of the major neurotransmitters that may be involved in the pathogenesis of bipolar disorder. Five polymorphisms in the GABRA5 gene, -754C>T in the promoter region, IVS1-21G>A, IVS2-26T>A, (*)302C>T in 3'-UTR of exon 5, and a CA repeat polymorphism in the 3' flanking region were examined in a Japanese population. IVS1-21G>A exhibited significant differences in the distribution of the genotype and allele frequency in bipolar I disorder patients but not in bipolar II disorder patients, compared with control subjects. The haplotype analysis showed that IVS1-21G>A/IVS2-26A>T was associated with bipolar I disorder, and the IVS1-21A/IVS2-26T haplotype was a negative risk factor for susceptibility to the disorders (odds ratio: 0.57, 95% confidence interval: 0.44-0.73). These results suggest that the GABRA5 gene may confer susceptibility to bipolar I disorder.
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ABSTRACT: The gabra5 gene is associated with pharmacological properties (myorelaxant, amnesic, anxiolytic) of benzodiazepines. It is tightly located (0.5 cM) close to the pink-eyed dilution (p) locus which encodes for fur color on mouse chromosome 7. We tested the putative role of the gabra5 gene in pharmacological properties of the full non specific agonist chlordiazepoxide (CDP), using behavioral and molecular approaches in mutated p/p mice and wild type F2 from crosses between two multiple markers inbred strain ABP/Le and C57BL/6By strain. From our results, using rotarod, light-dark box, elevated maze and radial arm maze tests, we demonstrate that p/p mice are more sensitive than WT to the sensory motor, anxiolytic and amnesic effect of CDP. This is associated with the presence of a haplotypic block on the murine chromosome 7 and with an up regulation of gabra5 mRNAs in hippocampi of p/p F2 mice.Behavioural brain research 06/2012; 233(2):474-82. DOI:10.1016/j.bbr.2012.05.041 · 3.39 Impact Factor
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ABSTRACT: Behavioral disinhibition (externalizing/impulsivity) and behavioral inhibition (internalizing/anxiety) may contribute to the development of alcohol abuse and dependence. But tests of person-by-environment interactions in predicting alcohol use disorders are needed. This study examined the extent to which interactions between behavioral disinhibition, behavioral inhibition and family management during adolescence predict alcohol abuse and alcohol dependence at age 27. This study used longitudinal data from a community sample of 808 men and women interviewed from ages 10 to 27 in the Seattle Social Development Project. Zero-order correlations followed by a series of nested regressions examined the relationships between individual characteristics (behavioral disinhibition and behavioral inhibition/anxiety) and environment (good vs. poor family management practices during adolescence) in predicting alcohol abuse and dependence criterion counts at age 27. Behavioral disinhibition and poor family management predicted increased likelihood of both alcohol abuse and alcohol dependence at age 27. Behavioral inhibition/anxiety was unrelated to both outcomes. Youths high in behavioral disinhibition were at increased risk for later alcohol abuse and dependence only in consistently poorly managed family environments. In consistently well-managed families, high levels of behavioral disinhibition did not increase risk for later alcohol abuse or dependence. Behavioral disinhibition increases risk for alcohol abuse and dependence in early adulthood only for individuals who experience poor family management during adolescence. Interventions seeking to reduce environmental risks by strengthening consistent positive family management practices may prevent later alcohol abuse and dependence among individuals at risk due to behavioral disinhibition.Drug and alcohol dependence 03/2010; 110(1-2):62-9. DOI:10.1016/j.drugalcdep.2010.02.005 · 3.28 Impact Factor
- International Review of Neurobiology 02/2005; 71:189-216. DOI:10.1016/S0074-7742(05)71009-6 · 2.46 Impact Factor