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.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Matochik, John A
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University of Oklahoma Health Sciences Center
Schools of Medicine
Oklahoma City
United States
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Acheson, Ashley; Franklin, Crystal; Cohoon, Andrew J et al. (2014) Anomalous temporoparietal activity in individuals with a family history of alcoholism: studies from the Oklahoma Family Health Patterns Project. Alcohol Clin Exp Res 38:1639-45
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
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
Lovallo, William R; Farag, Noha H; Sorocco, Kristen H et al. (2013) Early life adversity contributes to impaired cognition and impulsive behavior: studies from the Oklahoma Family Health Patterns Project. Alcohol Clin Exp Res 37:616-23
Roche, Daniel J O; King, Andrea C; Cohoon, Andrew J et al. (2013) Hormonal contraceptive use diminishes salivary cortisol response to psychosocial stress and naltrexone in healthy women. Pharmacol Biochem Behav 109:84-90
Lovallo, William R; Farag, Noha H; Sorocco, Kristen H et al. (2012) Lifetime adversity leads to blunted stress axis reactivity: studies from the Oklahoma Family Health Patterns Project. Biol Psychiatry 71:344-9
Acheson, Ashley; Vincent, Andrea S; Sorocco, Kristen H et al. (2011) Greater discounting of delayed rewards in young adults with family histories of alcohol and drug use disorders: studies from the Oklahoma family health patterns project. Alcohol Clin Exp Res 35:1607-13
Lovallo, William R (2011) Do low levels of stress reactivity signal poor states of health? Biol Psychol 86:121-8
Lovallo, William R; Robinson, Jennifer L; Glahn, David C et al. (2010) Acute effects of hydrocortisone on the human brain: an fMRI study. Psychoneuroendocrinology 35:15-20
Sorocco, Kristen H; Monnot, Marilee; Vincent, Andrea S et al. (2010) Deficits in affective prosody comprehension: family history of alcoholism versus alcohol exposure. Alcohol Alcohol 45:25-9

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