The Oklahoma Family Health Patterns project is an intensive study of psychological, behavioral, and stress reactivity characteristics in healthy young adults with a family history of alcoholism (FH+) with a goal of identifying characteristics that place these persons at elevated risk for the disorder. We have recently identified early life adverse experience (ELA), including physical and sexual abuse and separation from parents, as occurring with disproportionate impact in FH+, and we have shown that ELA accounts for diminished stress reactivity, behavioral impulsivity, and poor mood regulation, all of which are risk factors for alcohol and other substance use disorders. The impact of ELA in the FH+ population demands to be studied further in a Gene x Environment interaction given the known positive feedbacks between FH+ and ELA. Our goal is to carry out a G x E interaction study by genotyping our FH x ELA and examining the impact of genotype on the broad range of personal characteristics currently under study in this project.
Aim 1. Examine the differential impact of ELA on psychological and behavioral characteristics of FH+ vs. FH- groups using an expanded sample of volunteers.
Aim 2. Use our larger sample to carry out a Gene x Environment analysis to test specific alleles that are strongly suspected of influencing activity in brain motivational systems, expanding on work we initiated with NIAAA thanks to a supplement to this R01 (AA012207-S1).
Aim 3. Test specific aspects of temperament as endophenotypes linking FH and ELA to behavioral, cognitive, and stress reactivity as aspects of the person's phenotype.
Aim 4. Increase our recruitment base by screening and testing volunteers at a second site, the University of Texas HSC, San Antonio, where we currently conduct our neuroimaging studies. Alcoholism is a costly burden to society, but risk factors for alcoholism are poorly understood. The vast majorities of studies focuses on alcoholic patients but are unable to disentangle preexisting influences from the effects of alcohol intake history. Our high-risk study design can be of value by contrasting FH+ and FH- with regard to environmental contributors and genetic vulnerabilities that contribute to behavioral risk factors.

Public Health Relevance

Alcoholism is a costly burden to society, but risk factors for alcoholism are poorly understood. The vast majorities of studies focus on alcoholic patients but are unable to disentangle preexisting influences from the effects of alcohol intake history. Our high-risk study design can be of value by contrasting FH+ and FH- with regard to environmental contributors and genetic vulnerabilities that contribute to behavioral risk factors.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA012207-11
Application #
8654480
Study Section
Special Emphasis Panel (ZRG1-BBBP-D (02))
Program Officer
Matochik, John A
Project Start
2001-09-30
Project End
2019-04-30
Budget Start
2014-05-05
Budget End
2015-04-30
Support Year
11
Fiscal Year
2014
Total Cost
$552,647
Indirect Cost
$70,963
Name
University of Oklahoma Health Sciences Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
878648294
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
Lovallo, William R; Cohoon, Andrew J; Acheson, Ashley et al. (2018) Blunted stress reactivity reveals vulnerability to early life adversity in young adults with a family history of alcoholism. Addiction :
Buchanan, Tony W; Lovallo, William R (2018) The role of genetics in stress effects on health and addiction. Curr Opin Psychol 27:72-76
Lovallo, William R; Enoch, Mary-Anne; Sorocco, Kristen H et al. (2017) Joint Impact of Early Life Adversity and COMT Val158Met (rs4680) Genotypes on the Adult Cortisol Response to Psychological Stress. Psychosom Med 79:631-637
Acheson, Ashley; Lake, Sarah L; Bray, Bethany C et al. (2016) Early Adolescent Trajectories of Impulsiveness and Sensation Seeking in Children of Fathers with Histories of Alcohol and Other Substance Use Disorders. Alcohol Clin Exp Res 40:2622-2630
Lovallo, William R; Enoch, Mary-Anne; Acheson, Ashley et al. (2016) Early-Life Adversity Interacts with FKBP5 Genotypes: Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project. Neuropsychopharmacology 41:1724-32
Dager, Alecia D; McKay, D Reese; Kent Jr, Jack W et al. (2015) Shared genetic factors influence amygdala volumes and risk for alcoholism. Neuropsychopharmacology 40:412-20
Acheson, Ashley; Tagamets, Malle A; Winkler, Anderson et al. (2015) Striatal activity and reduced white matter increase frontal activity in youths with family histories of alcohol and other substance-use disorders performing a go/no-go task. Brain Behav 5:e00352
Sorocco, Kristen H; Carnes, Nathan C; Cohoon, Andrew J et al. (2015) Risk factors for alcoholism in the Oklahoma Family Health Patterns project: impact of early life adversity and family history on affect regulation and personality. Drug Alcohol Depend 150:38-45
Lovallo, William R; Enoch, Mary-Anne; Acheson, Ashley et al. (2015) Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G. Neuropsychopharmacology 40:2546-54
Acheson, Ashley; Wijtenburg, S Andrea; Rowland, Laura M et al. (2014) Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders. Hum Brain Mapp 35:5877-87

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