title: Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: association with allelic variation in GABRA2 and BDNF.
abstract: Offspring from families with multiple cases of alcohol dependence have a greater likelihood of developing alcohol dependence (AD) and related substance use disorders. Greater susceptibility for developing these disorders may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing and AD susceptibility. We examined the cerebellum of 71 adolescent/young adult high-risk (HR) offspring from families with multiple cases of alcohol dependence (multiplex families), and 60 low-risk (LR) controls with no family history of alcohol or drug dependence who were matched for age, gender, socioeconomic status and IQ, with attention given to possible effects of personal use of substances and maternal use during pregnancy. Magnetic resonance images were acquired on a General Electric 1.5-Tesla scanner and manually traced (BRAINS2) blind to clinical information. GABRA2 and BDNF variation were tested for their association with cerebellar volumes. High-risk offspring from multiplex AD families showed greater total volume of the cerebellum and total gray matter (GM), in comparison with LR controls. An interaction between allelic variation in GABRA2 and BDNF genes was associated with GM volumes, suggesting that inherited variation in these genes may promote early developmental differences in neuronal proliferation of the cerebellum.
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: syh50@imap.pitt.edu.
authors: Shirley Y
authors: SY
authors: Hill
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Shuhui
authors: S
authors: Wang
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Howard
authors: H
authors: Carter
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Kevin
authors: K
authors: Tessner
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Brian
authors: B
authors: Holmes
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Michael
authors: M
authors: McDermott
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Nicholas
authors: N
authors: Zezza
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Scott
authors: S
authors: Stiffler
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000437:Alcoholism / Q000235:genetics* / Q000473:pathology*; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002531:Cerebellum / Q000473:pathology*; D016241:Child of Impaired Parents; D005192:Family Health; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D011963:Receptors, GABA-A / Q000235:genetics*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C484841:GABRA2 protein, human; D011963:Receptors, GABA-A