Our goal is to develop a better understanding of central nervous system characteristics of persons at risk for alcoholism. Despite a large clinical literature on alcoholism, far less is known about the preclinical characteristics of persons at greatest risk for the disorder. The Oklahoma Family Health Patterns Project studies healthy young adults with and without a family history of alcoholism. Persons with a positive family history are four times as likely to develop alcohol use disorders as those with no such history, and this risk doubles in persons who also have antisocial and disinhibitory characteristics. The two tendencies are coinherited. Persons with both a positive family history and personal evidence of behavioral disinhibition are accordingly considered to be at High Risk of future alcoholism, and those lacking these factors are considered at Low Risk. Our major hypothesis is that High Risk persons have altered brain mechanisms that serve to produce normal emotional responses to the environment and have deficient regulation of overt behavior. While evidence points to altered communication between the limbic system and prefrontal cortex, confirmatory neuroimaging is lacking. This revised application pursues our recent finding that persons with a family history of alcoholism have differences in regional brain glucose metabolism in the resting state as compared to their counterparts with no such history. Preliminary findings are that FH+ have greater FDG uptake than FH- in structures involved in obtaining visual information (Rt. Middle &Sup. temp. gyrus) and obtaining rewards or assessing reward value to make relevant decisions (Left Cingulate and Caudate). This set of structures and functions is compatible with the greater activation seen in the hypothalamus, which may play a related role in preparation for obtaining such rewards. In contrast FH- have greater FDG uptake than FH+ in functions involving prefrontal regulatory controls: The right inferior frontal gyrus is involved in regulation of emotional and autonomic expression. This region is closely associated with functions involving conscious autonomic regulation in conjunction with the orbital frontal cortex having inputs to the hypothalamus and brainstem. The right middle frontal gyrus is involved in executive functions via extensive connections to the dorsolateral prefrontal cortex. This study will expand the resting database to allow a network analysis of resting metabolic activity of a network of brain areas concerned with resting metabolic differences in High-Risk persons. The present study will carry out a seed- based correlational analysis of default-mode and anti-default-mode function in our two risk groups. The planned studies are expected to yield new information concerning altered functioning in brain regions involved with cognition, decision-making, and behavioral regulation in young adults at high risk for future alcoholism.

Public Health Relevance

Alcohol abuse and dependence are behavioral disorders that are a burden to society. Despite a large literature on persons with alcohol dependence, much less is known about the preclinical characteristics of persons at greatest risk for the disorder, especially those with inherited risk factors. The present study examines resting brain metabolism in persons with a positive family history of alcoholism who also have disinhibited and antisocial tendencies that place them at High Risk of future alcoholism. Studies of High Risk individuals are valuable in characterizing behavioral characteristics of those who are vulnerable to alcoholism free of central nervous system effects secondary to heavy drinking. The proposed positron emission tomography study will provide new and useful information on the underlying brain functional characteristics of these High Risk individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA019691-01A1
Application #
8073927
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Matochik, John A
Project Start
2010-12-02
Project End
2013-11-30
Budget Start
2010-12-02
Budget End
2011-11-30
Support Year
1
Fiscal Year
2011
Total Cost
$192,661
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; 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 :
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
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) 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
Fox, Peter T; Lancaster, Jack L; Laird, Angela R et al. (2014) Meta-analysis in human neuroimaging: computational modeling of large-scale databases. Annu Rev Neurosci 37:409-34
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
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
Lovallo, William R (2013) Early life adversity reduces stress reactivity and enhances impulsive behavior: implications for health behaviors. Int J Psychophysiol 90:8-16
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

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