title: Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and its implication in executive functions in adult offspring of alcohol-dependent probands.
abstract: Impairment of executive functions (EFs) mediated by the prefrontal lobe is regarded as a cognitive endophenotype of alcohol dependence, being observed both in probands and in healthy offspring. Given its impact on the anatomy of the prefrontal cortex, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may well be involved in this specific endophenotype. Forty-six healthy adult children of alcoholics (HACA) and 82 healthy controls (HC) took part in the study. All the participants were assessed with the Diagnostic Interview for Genetic Studies, and their family histories of alcohol and substance use were assessed with the Family Informant Schedule and Criteria. The Trail Making Test, Arithmetic Switching Task, Stroop Color-Word Test and Wisconsin Card Sorting Test were administered to assess EFs. An overall executive factor score was calculated using factorial analyses. Genotyping of the BDNF Val66Met polymorphism was performed using the TaqMan® allelic discrimination assay. HACA had significantly lower EFs performance than HC. Genetic analysis showed that BDNF genotype distributions were in Hardy-Weinberg equilibrium in the HACA and HC. Genotype and allele distributions did not differ significantly between the two groups. Participants with the Met allele performed significantly more poorly than participants with the Val allele, and a group by allele interaction was observed, the BDNF Met allele being associated with a poorer executive factor score in the HACA group. These results suggest that the BDNF Val66Met polymorphism may contribute to alcohol dependence vulnerability via lower EFs performance.
authors.affiliation: Department of Psychiatry, Hôpital Robert Debré, 51100 Reims, France. fbenzerouk@chu-reims.fr
authors.forename: Farid
authors.initials: F
authors.lastname: Benzerouk
authors.forename: Fabien
authors.initials: F
authors.lastname: Gierski
authors.forename: Philip
authors.initials: P
authors.lastname: Gorwood
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ramoz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stefaniak
authors.forename: Bérengère
authors.initials: B
authors.lastname: Hübsch
authors.forename: Arthur
authors.initials: A
authors.lastname: Kaladjian
authors.forename: Frédéric
authors.initials: F
authors.lastname: Limosin
mesh_terms: D000328:Adult; D032721:Adult Children / Q000523:psychology*; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D000704:Analysis of Variance; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D056344:Executive Function; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human