This proposal addresses the hypothesis that disturbances of the serotonergic and noradrenergic systems interact in the expression of impulsive, aggressive, and/or suicidal behavior in the personality disorders and major depressive disorder (MDD). Both suicidal and aggressive behavior account for considerable morbidity in the psychiatric disorders, and the elucidation of their pathophysiology and associated implications for treatment represents a formidable challenge for biological psychiatry. We intend to examine personality disorder and depressed patients to define potentially differential and interactive contributions of the serotonergic and noradrenergic systems to externally directed impulsivity and aggression, on the one hand, and self-directed suicidal behavior on the other; to study the role of gender in the expression of and the neurobiology of impulsivity, aggression, and suicidal behavior; and to examine the relationship between """"""""net"""""""" or postsynaptic responses to challenge studies and basal/ metabolite CSF or plasma measures in each system. To address these questions, the functioning of, and the relationship between, the serotonergic (prolactin response to fenfluramine and cerebrospinal fluid [CSF] 5- hydroxyindoleacetic acid) and noradrenergic (growth hormone response to clonidine, CSF 3-methoxy-4-hydroxyphenylglycol, and basal plasma norepinephrine) systems and measures of aggression, impulsivity and suicidality, will be assessed in 75 male and 75 female patients with:DSM- III-R personality disorder, in 50 male and 50 female patients with major depression and without a personality disorder from DSM-III-R Cluster A or B, and in 25 male and 25 female age-matched normal controls.
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