This career (K01) award applies specific funding, 85% research time, and a 3-year plan to develop the candidate's experience and expertise in the clinical research of alcoholism through the analysis of an established database from a large Danish birth cohort. The candidate will advance her understanding of clinical epidemiology and psychopathology through practical training and didactic lectures. Expert clinical and statistical consultation will be offered through the University of Kansas Medical Center and the Copenhagen Institute of Preventive Medicine. Close internal mentorship and external consultation will be provided by established senior scientists to facilitate the candidates' development into an independent clinical researcher. The proposed research tests the main hypothesis that neurodevelopmental disruption in infancy increases vulnerability to alcoholism in adults. The theoretical basis for this relationship stems from the naturally elevated vulnerability of neonates to oxidative brain damage at birth. Selective destruction of myelin-producing oligodendrocytes in response to hypoxic trauma at birth has been associated with lasting dysfunction of reward-related limbic circuits in animal models. Such early damage to developing limbic structures could alter the response of affected individuals to rewarding stimuli and influence their vulnerability to alcoholism and addictions later in life. Study subjects will be drawn from a large birth cohort collected in Copenhagen from 1959 to 1961. The database contains extensive, detailed information relating to the pregnancy and birth of 9,125 Danish subjects. This includes specific information relating to the physical condition of subjects at birth, day 5 and 1 yr of age. The Danish Central Psychiatric Register, a national register of all psychiatric diagnosis and admissions as well as data from local municipal alcoholism treatment clinics, will provide information about the psychiatric outcomes of the now adult study subjects. The Danish National Hospital Register will provide additional information about hospital admissions for alcoholismrelated medical conditions since the 1990s. The study uses perinatal data to predict adult outcomes in order to identify risk factors and protective effects against the development of alcoholism. A parsimonious, multivariance model for the development of alcoholism will be constructed from the identified variables and established risk factors for alcoholism (gender and family history of alcoholism). ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AA015935-02
Application #
7425098
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Noronha, Antonio
Project Start
2007-05-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
2
Fiscal Year
2008
Total Cost
$130,627
Indirect Cost
Name
University of Kansas
Department
Psychiatry
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Manzardo, A M; Gunewardena, S; Butler, M G (2013) Over-expression of the miRNA cluster at chromosome 14q32 in the alcoholic brain correlates with suppression of predicted target mRNA required for oligodendrocyte proliferation. Gene 526:356-63
Madarasz, Wendy; Manzardo, Ann; Mortensen, Erik Lykke et al. (2012) Forty-five-year mortality rate as a function of the number and type of psychiatric diagnoses found in a large Danish birth cohort. Can J Psychiatry 57:505-11
Manzardo, A M; Henkhaus, R S; Butler, M G (2012) Global DNA promoter methylation in frontal cortex of alcoholics and controls. Gene 498:5-12
Manzardo, Ann M; Henkhaus, Rebecca; Hidaka, Brandon et al. (2012) X chromosome inactivation in women with alcoholism. Alcohol Clin Exp Res 36:1325-9
Sorensen, Holger J; Manzardo, Ann M; Knop, Joachim et al. (2011) The contribution of parental alcohol use disorders and other psychiatric illness to the risk of alcohol use disorders in the offspring. Alcohol Clin Exp Res 35:1315-20
Manzardo, Ann M; Madarasz, Wendy V; Penick, Elizabeth C et al. (2011) Effects of premature birth on the risk for alcoholism appear to be greater in males than females. J Stud Alcohol Drugs 72:390-8
Knop, Joachim; Penick, Elizabeth C; Nickel, Elizabeth J et al. (2009) Childhood ADHD and conduct disorder as independent predictors of male alcohol dependence at age 40. J Stud Alcohol Drugs 70:169-77