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).
