title: Shared genetic factors influence amygdala volumes and risk for alcoholism.
abstract: Alcohol abuse and dependence (alcohol use disorders, AUDs) are associated with brain shrinkage. Subcortical structures including the amygdala, hippocampus, ventral striatum, dorsal striatum, and thalamus subserve reward functioning and may be particularly vulnerable to alcohol-related damage. These structures may also show pre-existing deficits impacting the development and maintenance of AUD. It remains unclear whether there are common genetic features underlying both subcortical volumes and AUD. In this study, structural brain images were acquired from 872 Mexican-American individuals from extended pedigrees. Subcortical volumes were obtained using FreeSurfer, and quantitative genetic analyses were performed in SOLAR. We hypothesized the following: (1) reduced subcortical volumes in individuals with lifetime AUD relative to unrelated controls; (2) reduced subcortical volumes in individuals with current relative to past AUD; (3) in non-AUD individuals, reduced subcortical volumes in those with a family history of AUD compared to those without; and (4) evidence for common genetic underpinnings (pleiotropy) between AUD risk and subcortical volumes. Results showed that individuals with lifetime AUD showed larger ventricular and smaller amygdala volumes compared to non-AUD individuals. For the amygdala, there were no differences in volume between current vs past AUD, and non-AUD individuals with a family history of AUD demonstrated reductions compared to those with no such family history. Finally, amygdala volume was genetically correlated with the risk for AUD. Together, these results suggest that reduced amygdala volume reflects a pre-existing difference rather than alcohol-induced neurotoxic damage. Our genetic correlation analysis provides evidence for a common genetic factor underlying both reduced amygdala volumes and AUD risk.
authors: 1] Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: Alecia D
authors: AD
authors: Dager
authors: 1] Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: D Reese
authors: DR
authors: McKay
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Jack W
authors: JW
authors: Kent
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Joanne E
authors: JE
authors: Curran
authors: 1] Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: Emma
authors: E
authors: Knowles
authors: 1] Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: Emma
authors: E
authors: Sprooten
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Harald H H
authors: HH
authors: Göring
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Thomas D
authors: TD
authors: Dyer
authors: 1] Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: Godfrey D
authors: GD
authors: Pearlson
authors: Department of Psychiatry, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
authors: Rene L
authors: RL
authors: Olvera
authors: 1] Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA [2] South Texas Veterans Health System, San Antonio, TX, USA.
authors: Peter T
authors: PT
authors: Fox
authors: Department of Psychiatry, Oklahoma University Heath Science Center and Veterans Administration Medical Center, Oklahoma City, OK, USA.
authors: William R
authors: WR
authors: Lovallo
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Ravi
authors: R
authors: Duggirala
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Laura
authors: L
authors: Almasy
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: John
authors: J
authors: Blangero
authors: 1] Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: David C
authors: DC
authors: Glahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019973:Alcohol-Related Disorders / Q000235:genetics* / Q000473:pathology*; D000679:Amygdala / Q000473:pathology*; D005190:Family; D005260:Female; D058685:Genetic Pleiotropy; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008875:Middle Aged; D009929:Organ Size; D012306:Risk; D055815:Young Adult