This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project has two sets of hypotheses: Treatment Hypotheses and Neuro-Biological Correlates of Treatment Hypotheses. Treatment Hypotheses include: 1. Treatment with Fluoxetine and Divalproes will be more efficacious than Placebo in reducing impulsive aggressive behavior in subjects with Intermittent Explosive Disorder (IED) overall and, 2. 'High Aggressive' IED Subjects will respond preferentially to treatment with Fluoxetine (both aims/hypotheses to be funded by NIMH). The Neuobiological Correlates Hypotheses include: 1. Platelet 5-HT Transporter binding will correlate with the anti-aggressive response to Fluoxetine but not to Divalproex; 2. Plasma GABA will correlate with the anti-aggressive response to Divalproex but not to Fluoxetine; 3. Assessment of aggression impulsivity, and social/emotional information processing will correlate with the anti-aggressive response to both Fluoxetine and Divalproex and, 4. DNA Polymorphisms of 5-Htrelevant genes will correlate with the anti-aggressive response to Fluoxetine and DNA Polymorphisms of GABA relevant genes will correlate with the anti-aggressive response to Divalproex. The design of the study is a fourteen week (twelve-weeks for active drug), double-blind, randomized, placebo-controlled trial of fluoxetine and divaloproex in IED subjects stratified by lifetime aggressiveness (I.e. Life History of Aggression Score: 'Moderate Aggression'=LHA<17, 'High Aggression'=LHA>18). CRC resources are requested primarily for ancillary services in obtaining medical screening and medical surveillance testing and in obtaining samples for Platelet 5-HT Transporter Binding, Plasma GABA Concentration, and in obtaining blood samples for DNA Extraction for pharmacogenetic analysis.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
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University of Chicago
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