A defect in central serotonergic regulation of impulse, affect, and behavior is associated with impulsive-aggressive behavior, personality disorder, affective disorder, suicidal behavior, and alcoholism in adults. This project addresses the relationship between diminished central serotonergic function in older adolescents (aged 16-19) and the diagnosis and severity of Alcohol Use Disorders, Conduct Disorder, impulsivity and aggressivity, suicidal, and violent behaviors. Serotonergic function is assessed through pharmacologic challenge with dl-fenfluramine (1 mg/kg) and the simultaneous measurement of neuroendocrine responses through blood sampling of prolactin and cortisol, and prefrontal cortical activation responses through fMRI techniques. Dynamic contrast fMRI study of hemodynamic responses in prefrontal cortex during activation with fenfluramine addresses the serotonergic responsiveness of an area intimately involved in self-regulation of impulse, affect, and behavior, while morphometric study by high resolution MRI may reveal structural differences. Eighty adolescents, half with Alcohol Use Disorders and half without will be studied in PAARC Years 06 and 07, with one and three year follow-ups to determine whether neuroendocrine and prefrontal cortical activation response variables predict adverse psychosocial outcomes. Adverse outcomes associated with these psychobiologic variables include: progression of severity of Alcohol Use Disorder, development of adult criteria for ASPD, affective disorders, suicidal, and violent behavior. This study will contribute to our understanding of the psychobiology of adolescent Alcohol Use Disorders and the identification of biologic risk factors that may predict long term adverse psychosocial consequences.
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