This proposed project has three (3) specific aims.
The first aim i s to compare the efficacy of two different psychopharmacologic agents (fluoxetine or divalproex sodium) in the treatment of impulsive aggressive behavior by men and women with Intermittent Explosive Disorder (lED).
The second aim i s to explore the serotonergic correlates of clinical response to these treatment modalities.
The third aim i s to compare lED subjects and Normal Control subjects in regard to the assessments of 5-HT receptor function and to the assessment of the 5-HT Transporter. In the context of the first two aims, we will also be testing the possibility of a differential anti-aggressive response to treatment with fluoxetine or divalproex in lED subjects as a function of """"""""severity of lifetime aggressiveness"""""""" (e.g., """"""""Moderately Aggressive"""""""" vs. """"""""Highly Aggressive""""""""lED subjects). Specifically, we hypothesize that fluoxetine is preferentially efficacious in """"""""moderately aggressive"""""""" lED and that divalproex is preferentially efficacious in """"""""highly aggressive"""""""" lED. In additIon, this study proposes to more fully examine the nature of the relationship between pretreatment 5-HT receptor function and anti-aggressive response to these agents. Biologic evaluation of the 5-HT system will include m-CPP and ipsapirone Challenges, Platelet Tritiated (3H) Paroxetine 5-HT Transporter Binding and 5-HTRelated DNA Polymorphisms. m-CPP Challenge is included to assess the function of post-synaptic 5-HT-2c receptors (ACTH and Thermal Responses) while Ipsapirone Challenge is included to assess the function of both pre-synaptic 5-HT-1a (Thermal Response)and post-synaptic 5-HT-1a (ACTH Response)receptors. Platelet 5-HTT binding is assessed in this context because fluoxetine (but not divalproex) acts at brain 5- HTT sites and because Platelet (and brain) 5-HTT binding correlates inversely with lifetime aggressiveness. Participants will be randomly assigned, and stratified by lifetime aggressiveness (i.e, Life History of Aggression Score: """"""""Moderate Aggression"""""""" = LHA < 17; """"""""High Aggression"""""""" = LHA > 18), to one of three (3) treatment conditions as follows: 1) Fluoxetine; 2) Divalproex Sodium; Placebo. Duration of treatment will be twelve weeks.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Rudorfer, Matthew V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Chicago
Schools of Medicine
United States
Zip Code
Rynar, Lauren; Coccaro, Emil F (2018) Psychosocial impairment in DSM-5 intermittent explosive disorder. Psychiatry Res 264:91-95
Mosti, Caterina; Coccaro, Emil F (2018) Mild Traumatic Brain Injury and Aggression, Impulsivity, and History of Other- and Self-Directed Aggression. J Neuropsychiatry Clin Neurosci 30:220-227
Coccaro, Emil F; Fanning, Jennifer; Lee, Royce (2017) Development of a social emotional information processing assessment for adults (SEIP-Q). Aggress Behav 43:47-59
Coccaro, Emil F; Keedy, Sarah K; Gorka, Stephanie M et al. (2016) Differential fMRI BOLD responses in amygdala in intermittent explosive disorder as a function of past Alcohol Use Disorder. Psychiatry Res Neuroimaging 257:5-10
Coccaro, Emil F; Fridberg, Daniel J; Fanning, Jennifer R et al. (2016) Substance use disorders: Relationship with intermittent explosive disorder and with aggression, anger, and impulsivity. J Psychiatr Res 81:127-32
Coccaro, Emil F; Lee, Royce; Groer, Maureen W et al. (2016) Toxoplasma gondii infection: relationship with aggression in psychiatric subjects. J Clin Psychiatry 77:334-41
Coccaro, Emil F; Lee, Royce; Fanning, Jennifer R et al. (2016) Tryptophan, kynurenine, and kynurenine metabolites: Relationship to lifetime aggression and inflammatory markers in human subjects. Psychoneuroendocrinology 71:189-96
Fanning, Jennifer R; Lee, Royce; Coccaro, Emil F (2016) Comorbid intermittent explosive disorder and posttraumatic stress disorder: Clinical correlates and relationship to suicidal behavior. Compr Psychiatry 70:125-33
Coccaro, Emil F; Solis, Oscar; Fanning, Jennifer et al. (2015) Emotional intelligence and impulsive aggression in Intermittent Explosive Disorder. J Psychiatr Res 61:135-40
Coccaro, Emil F; Lee, Royce; McCloskey, Michael et al. (2015) Morphometric analysis of amygdla and hippocampus shape in impulsively aggressive and healthy control subjects. J Psychiatr Res 69:80-6

Showing the most recent 10 out of 26 publications