Our long-term goal is to develop a better understanding of predisposing motivational characteristics of persons at risk for alcoholism. Alcohol addiction is a behavioral disorder with genetic and environmental contributions. Increased risk for alcoholism in persons with a positive family history is an expression of more basic inherited traits. These traits are thought to derive from altered activity of brain regions regulating emotional experience and expression. The present project will examine persons with a family history of alcoholism and classify them according to their cortisol response to naltrexone, an opiate receptor blocker. The magnitude of cortisol response to naltrexone is a useful indicator of an abnormally elevated central opioid regulation. This elevation in opioid function is also an indicator of differential functioning of other brain regulatory systems. These systems have an impact on functioning of the limbic system and prefrontal cortex, and in turn may provide insights into underlying alterations in motivation-related behavior in persons who are at high risk for alcoholism. We plan to test 200 healthy volunteers, 100 with a family history of alcoholism, 100 without. We predict that elevated central opioid activation in high-risk individuals will be observable in four domains of function: 1) Behavioral undercontrol: the person's temperamental balance of positive to negative affect should be less stable and weighted toward dysphoria. 2) Cognitive processing will be impaired on tests or working memory. 3) Choice behaviors will show biases toward risk-taking and impulsivity under motivational conditions. Tests of behavioral economics (delay-discounting) will show a short time horizon. 4) Visceral responses to psychological stress will be blunted, with reduced responses in the stress hormone, cortisol, and autonomic measures controlling the heart. Our longer-term goal is to perform annual follow-ups of subjects who have taken part in the study to seek factors that determine long-term drinking patterns. This project seeks to understand psychological and behavioral characteristics of young adults who are children of alcoholics to identify those personal characteristics that put them at high risk for future alcoholism. Prevention of complex disorders such as alcoholism requires early identification of those persons who are most at risk, and this project seeks to provide new information about such risk.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012207-08
Application #
7798556
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Matochik, John A
Project Start
2001-09-30
Project End
2013-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
8
Fiscal Year
2010
Total Cost
$344,750
Indirect Cost
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; 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
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
Acheson, Ashley; Wijtenburg, S Andrea; Rowland, Laura M et al. (2014) Assessment of whole brain white matter integrity in youths and young adults with a family history of substance-use disorders. Hum Brain Mapp 35:5401-13
Acheson, Ashley; Tagamets, Malle A; Rowland, Laura M et al. (2014) Increased forebrain activations in youths with family histories of alcohol and other substance use disorders performing a Go/NoGo task. Alcohol Clin Exp Res 38:2944-51
Lovallo, William R; Enoch, Mary-Anne; Yechiam, Eldad et al. (2014) Differential impact of serotonin transporter activity on temperament and behavior in persons with a family history of alcoholism in the Oklahoma Family Health Patterns Project. Alcohol Clin Exp Res 38:1575-81

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