Among the various sociologic, psychologic, and biogenetic factors associated with impulsive, as opposed to premeditated, human aggression, the most consistent biological factor appears to be a reduction in central serotonergic (5-HT) neurotransmission. 5-HT's role in the regulation of impulsive aggressive behavior is thought to arise from its role in neuronal inhibition, through which it constrains behavioral action in response to an outward (or inward) aversive stimulus or provocation. In this formulation, 5-HT acts to restrain the individual from assaulting the object of stimulus and other neuronal systems (e.g., catecholamines) modulate the detection of, and/or the response to, the aversive stimulus. At this time, there is little knowledge regarding this role of specific 5-HT receptor subsystems and of the role of catecholamines, such as norepinephrine, in the mediation of these behaviors.

In this renewal of the Principal Investigator's RSDA (Level II) Application, the PI proposes to conduct expanded and systematic studies regarding the relationship between indices of 5-HT-1a, 5-HT-2a/2c, and alpha-2 NE function and comprehensive indices of impulsive aggressive and suicidal behaviors in personality disorder (PD) subjects. In addition, the PI plans to expand his clinical drug trial research regarding the antiaggressive efficacy of Fluoxetine by conducting a nine-month continuation and relapse/remission study in PD subjects. A new direction in this area of antiaggressive efficacy is represented by a combined Fluoxetine/Cognitive-Behavioral treatment trial in male spouse abusers. The development, during the current grant, of reliable criteria for a disorder of Impulsive Aggression will allow further work (i.e., Family Study, DNA Polymorphism Study, Epidemiologic Survey) to test the full spectrum of construct validity for impulsive aggressive behavior as a clinical entity. The skills to implement these and other studies will be acquired during the next five years if this RSDA award.

K02MH000951

1991-09-30

2002-04-30