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.Neuropsychopharmacology advance online publication, 3 September 2014;doi:10.1038/npp.2014.187.
| Original language | English (US) |
|---|---|
| Journal | Neuropsychopharmacology |
| DOIs | |
| State | Accepted/In press - Jul 31 2014 |
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ASJC Scopus subject areas
- Psychiatry and Mental health
- Pharmacology
Cite this
Shared Genetic Factors Influence Amygdala Volumes and Risk for Alcoholism. / Dager, Alecia D.; McKay, D. Reese; Kent, Jack W.; Curran, Joanne E.; Knowles, Emma; Sprooten, Emma; Göring, Harald H.H.; Dyer, Thomas D.; Pearlson, Godfrey D.; Olvera, Rene L; Fox, Peter T; Lovallo, William R.; Duggirala, Ravi; Almasy, Laura; Blangero, John; Glahn, David C.
In: Neuropsychopharmacology, 31.07.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Shared Genetic Factors Influence Amygdala Volumes and Risk for Alcoholism
AU - Dager, Alecia D.
AU - McKay, D. Reese
AU - Kent, Jack W.
AU - Curran, Joanne E.
AU - Knowles, Emma
AU - Sprooten, Emma
AU - Göring, Harald H.H.
AU - Dyer, Thomas D.
AU - Pearlson, Godfrey D.
AU - Olvera, Rene L
AU - Fox, Peter T
AU - Lovallo, William R.
AU - Duggirala, Ravi
AU - Almasy, Laura
AU - Blangero, John
AU - Glahn, David C.
PY - 2014/7/31
Y1 - 2014/7/31
N2 - 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.Neuropsychopharmacology advance online publication, 3 September 2014;doi:10.1038/npp.2014.187.
AB - 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.Neuropsychopharmacology advance online publication, 3 September 2014;doi:10.1038/npp.2014.187.
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UR - http://www.scopus.com/inward/citedby.url?scp=84906723108&partnerID=8YFLogxK
U2 - 10.1038/npp.2014.187
DO - 10.1038/npp.2014.187
M3 - Article
C2 - 25079289
AN - SCOPUS:84926662174
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
ER -