This is the second submission of a proposal which was initially reviewed in response to an RFA entitled """"""""Neurobiological Mechanisms of Adolescent Alcohol Abuse"""""""" (AA-99-002). We propose a 3 year cross sectional investigation to non-invasively examine the effects of alcohol use disorders (AUD) (defined as DSM-IV alcohol dependence or abuse) and posttraumatic stress disorder (PTSD) on hippocampal development in adolescents. The developing hippocampus may be particularly vulnerable to the toxic effects of alcohol. We have recently published our pilot investigation comparing medically healthy adolescents and young adults with AUD and age and sex matched controls on hippocampal volumes. We found a decrease in total hippocampal volume in AUD subjects compared with matched controls. A substantial percentage of adolescents with AUD are comorbid with PTSD secondary to a history of childhood physical and sexual abuse. Previous studies have suggested that childhood traumatic experiences, which lead to a diagnosis of PTSD, may have adverse effects of brain development. This study will therefore examine the main effect of AUD, the main effect of PTSD and the interaction of AUD and PTSD on adolescent hippocampal development. We hypothesize that AUD and PTSD both adversely effect hippocampal volume and hippocampal function. Recruitment, assessment, and administration of this investigation will occur primarily through the Pittsburgh Adolescent Alcohol Research Center (PAARC), an NIAAA Alcohol Research Center. Four adolescent groups will be compared: 1) AUD adolescents with PTSD (n=36), 2) AUD adolescents with PTSD (n=36), 3) adolescents with PTSD and with or without a current of lifetime diagnosis of AUD (n=36), and 4) age, sex, and sociodemographically matched healthy community control adolescents (n=3 6). This design will determine the effects of AUD while controlling for the effects of PTSD and environmental variables. In addition to examining the differences among these groups, the effects of AUD age of onset, AUD severity, as well as alcohol consumption quantity, frequency, and duration, on adolescent hippocampal development will also be examined.
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