Amygdala Volume in Offspring from Multiplex for Alcohol Dependence Families: The Moderating Influence of Childhood Environment and 5-HTTLPR Variation

Overview

Journal J Alcohol Drug Depend

Publisher Omics Publishing Group

Date 2014 Oct 7

PMID 25285331

Citations 23

Authors

Shirley Y Hill

Shuhui Wang

Howard Carter

Michael D McDermott

Nicholas Zezza

Scott Stiffler

Affiliations

Soon will be listed here.

Abstract

Background: The increased susceptibility for developing alcohol dependence seen in offspring from families with alcohol dependence may be related to structural and functional differences in brain circuits that influence emotional processing. Early childhood environment, genetic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) of the SLCA4 gene and allelic variation in the Brain Derived Neurotrophic Factor (BDNF) gene have each been reported to be related to volumetric differences in the temporal lobe especially the amygdala.

Methods: Magnetic resonance imaging was used to obtain amygdala volumes for 129 adolescent/young adult individuals who were either High-Risk (HR) offspring from families with multiple cases of alcohol dependence (N=71) or Low-Risk (LR) controls (N=58). Childhood family environment was measured prospectively using age-appropriate versions of the Family Environment Scale during a longitudinal follow-up study. The subjects were genotyped for Brain-Derived Neurotrophic Factor (BDNF) Val66Met and the serotonin transporter polymorphism (5-HTTLPR). Two family environment scale scores (Cohesion and Conflict), genotypic variation, and their interaction were tested for their association with amygdala volumes. Personal and prenatal exposure to alcohol and drugs were considered in statistical analyses in order to more accurately determine the effects of familial risk group differences.

Results: Amygdala volume was reduced in offspring from families with multiple alcohol dependent members in comparison to offspring from control families. High-Risk offspring who were carriers of the S variant of the 5-HTTLPR polymorphism had reduced amygdala volume in comparison to those with an LL genotype. Larger amygdala volume was associated with greater family cohesion but only in Low-Risk control offspring.

Conclusions: Familial risk for alcohol dependence is an important predictor of amygdala volume even when removing cases with significant personal exposure and covarying for prenatal exposure effects. The present study provides new evidence that amygdala volume is modified by 5-HTTLPR variation in High-Risk families.

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References

Green J, McLaughlin K, Berglund P, Gruber M, Sampson N, Zaslavsky A . Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry. 2010; 67(2):113-23. PMC: 2822662. DOI: 10.1001/archgenpsychiatry.2009.186. View

Feinn R, Nellissery M, Kranzler H . Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2005; 133B(1):79-84. DOI: 10.1002/ajmg.b.30132. View

Hill S, Wang S, Kostelnik B, Carter H, Holmes B, McDermott M . Disruption of orbitofrontal cortex laterality in offspring from multiplex alcohol dependence families. Biol Psychiatry. 2008; 65(2):129-36. PMC: 3280899. DOI: 10.1016/j.biopsych.2008.09.001. View

Takahashi T, Suzuki M, Tsunoda M, Kawamura Y, Takahashi N, Tsuneki H . Association between the brain-derived neurotrophic factor Val66Met polymorphism and brain morphology in a Japanese sample of schizophrenia and healthy comparisons. Neurosci Lett. 2008; 435(1):34-9. DOI: 10.1016/j.neulet.2008.02.004. View

Pilowsky D, Keyes K, Hasin D . Adverse childhood events and lifetime alcohol dependence. Am J Public Health. 2008; 99(2):258-63. PMC: 2622772. DOI: 10.2105/AJPH.2008.139006. View

Sullivan E . Compromised pontocerebellar and cerebellothalamocortical systems: speculations on their contributions to cognitive and motor impairment in nonamnesic alcoholism. Alcohol Clin Exp Res. 2003; 27(9):1409-19. DOI: 10.1097/01.ALC.0000085586.91726.46. View

Grossman R, Buchsbaum M, Yehuda R . Neuroimaging studies in post-traumatic stress disorder. Psychiatr Clin North Am. 2002; 25(2):317-40, vi. DOI: 10.1016/s0193-953x(01)00011-9. View

Peterson J, Pihl R, Seguin J, Finn P, Stewart S . Heart-rate reactivity and alcohol consumption among sons of male alcoholics and sons of non-alcoholics. J Psychiatry Neurosci. 1993; 18(4):190-8. PMC: 1188528. View

Magnotta V, Harris G, Andreasen N, OLeary D, Yuh W, Heckel D . Structural MR image processing using the BRAINS2 toolbox. Comput Med Imaging Graph. 2002; 26(4):251-64. DOI: 10.1016/s0895-6111(02)00011-3. View

10.

Zimmermann U, Spring K, Kunz-Ebrecht S, Uhr M, Wittchen H, Holsboer F . Effect of ethanol on hypothalamic-pituitary-adrenal system response to psychosocial stress in sons of alcohol-dependent fathers. Neuropsychopharmacology. 2004; 29(6):1156-65. DOI: 10.1038/sj.npp.1300395. View

11.

van der Zwaluw C, Engels R . Gene-environment interactions and alcohol use and dependence: current status and future challenges. Addiction. 2009; 104(6):907-14. DOI: 10.1111/j.1360-0443.2009.02563.x. View

12.

Griesler P, Kandel D . The impact of maternal drinking during and after pregnancy on the drinking of adolescent offspring. J Stud Alcohol. 1998; 59(3):292-304. DOI: 10.15288/jsa.1998.59.292. View

13.

Spadoni A, Norman A, Schweinsburg A, Tapert S . Effects of family history of alcohol use disorders on spatial working memory BOLD response in adolescents. Alcohol Clin Exp Res. 2008; 32(7):1135-45. PMC: 2532854. DOI: 10.1111/j.1530-0277.2008.00694.x. View

14.

Hu X, Lipsky R, Zhu G, Akhtar L, Taubman J, Greenberg B . Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet. 2006; 78(5):815-826. PMC: 1474042. DOI: 10.1086/503850. View

15.

Rao H, Gillihan S, Wang J, Korczykowski M, Sankoorikal G, Kaercher K . Genetic variation in serotonin transporter alters resting brain function in healthy individuals. Biol Psychiatry. 2007; 62(6):600-6. DOI: 10.1016/j.biopsych.2006.11.028. View

16.

McHugh R, Hofmann S, Asnaani A, Sawyer A, Otto M . The serotonin transporter gene and risk for alcohol dependence: a meta-analytic review. Drug Alcohol Depend. 2010; 108(1-2):1-6. PMC: 2835838. DOI: 10.1016/j.drugalcdep.2009.11.017. View

17.

Kobiella A, Reimold M, Ulshofer D, Ikonomidou V, Vollmert C, Vollstadt-Klein S . How the serotonin transporter 5-HTTLPR polymorphism influences amygdala function: the roles of in vivo serotonin transporter expression and amygdala structure. Transl Psychiatry. 2012; 1:e37. PMC: 3309509. DOI: 10.1038/tp.2011.29. View

18.

Finn P, Zeitouni N, Pihl R . Effects of alcohol on psychophysiological hyperreactivity to nonaversive and aversive stimuli in men at high risk for alcoholism. J Abnorm Psychol. 1990; 99(1):79-85. DOI: 10.1037//0021-843x.99.1.79. View

19.

Wojnar M, Brower K, Strobbe S, Ilgen M, Matsumoto H, Nowosad I . Association between Val66Met brain-derived neurotrophic factor (BDNF) gene polymorphism and post-treatment relapse in alcohol dependence. Alcohol Clin Exp Res. 2009; 33(4):693-702. PMC: 2928673. DOI: 10.1111/j.1530-0277.2008.00886.x. View

20.

Uhart M, Oswald L, McCaul M, Chong R, Wand G . Hormonal responses to psychological stress and family history of alcoholism. Neuropsychopharmacology. 2006; 31(10):2255-63. DOI: 10.1038/sj.npp.1301063. View