The applicant proposes to acquire new training in magnetic resonance spectroscopy and neuroendocrinology. These two areas of investigation will expand his clinical research expertise and further his research endeavors in attempting to better understand the neuroanatomic and neuroendocrinological underpinnings of bipolar disorder. The research training will then be used to translate these potential research gains into clinical applications to better understand and ultimately treat major psychiatric illnesses. This study will examine the impact of alcohol on the biochemistry, neuroendocrinology, and neuropsychological functioning of bipolar illness. The lifetime prevalence rate of alcohol abuse comorbidity in bipolar disorder is the highest of all Axis I diagnoses; furthermore, the presence of alcohol abuse in bipolar disorder is associated with a decreased response rate to the gold standard treatment lithium carbonate. Thus, by prevalence data and inadequate treatment response, this represents an enormous public health problem. In a cross-sectional analysis, patients with bipolar disorder and comorbid alcohol abuse or dependence, patients with bipolar illness without comorbid alcohol abuse or dependence, and age matched healthy controls will undergo 1 H-MR spectroscopy, Dexamethasone/CRH neuroendocrine challenge, and neuropsychological evaluation assessing executive function, verbal memory, and working memory. This study will evaluate whether there are differences amongst the three groups and if there is a relationship between N-acetylaspartate (NAA), hypothalamic-pituitary adrenal axis function, and neuropsychological functioning. These variables will also be evaluated as to their predictive potential for relapse under naturalistic follow-up where mood stability, alcohol craving and relapse, medication compliance, and functional capacity will be monitored. This naturalistic follow-up period may identify preliminary neurobiological factors associated with relapse and provide direction for further controlled interventional study.
