Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
7K02MH000951-09
Application #
2889796
Study Section
Special Emphasis Panel (ZMH1-NRB-L (M2))
Project Start
1991-09-30
Project End
2001-04-30
Budget Start
1998-11-11
Budget End
1999-04-30
Support Year
9
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Mcp Hahnemann University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19102

  Publications

Coccaro, Emil F (2011) Intermittent explosive disorder: development of integrated research criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Compr Psychiatry 52:119-25
Phan, K Luan; Lee, Royce; Coccaro, Emil F (2011) Personality predictors of antiaggressive response to fluoxetine: inverse association with neuroticism and harm avoidance. Int Clin Psychopharmacol 26:278-83
Dakwar, Elias; Popii, Marias; Coccaro, Emil F (2011) Lifetime history of cigarette smoking associated with aggression and impulsivity in both healthy and personality disordered volunteers. J Pers Disord 25:645-55
Lee, Royce; Coccaro, Emil F (2010) Plasma homovanillic acid correlates inversely with history of childhood trauma in personality disordered and healthy control adults. J Neural Transm (Vienna) 117:1327-34
Coccaro, Emil F; Lee, Royce; Kavoussi, Richard J (2010) Aggression, suicidality, and intermittent explosive disorder: serotonergic correlates in personality disorder and healthy control subjects. Neuropsychopharmacology 35:435-44
Coccaro, Emil F; Lee, Royce; Kavoussi, Richard J (2010) Inverse relationship between numbers of 5-HT transporter binding sites and life history of aggression and intermittent explosive disorder. J Psychiatr Res 44:137-42
Almeida, Marcela; Lee, Royce; Coccaro, Emil F (2010) Cortisol responses to ipsapirone challenge correlate with aggression, while basal cortisol levels correlate with impulsivity, in personality disorder and healthy volunteer subjects. J Psychiatr Res 44:874-80
Ferguson, Sherise D; Coccaro, Emil F (2009) History of mild to moderate traumatic brain injury and aggression in physically healthy participants with and without personality disorder. J Pers Disord 23:230-9
Lee, Royce; Ferris, Craig; Van de Kar, L D et al. (2009) Cerebrospinal fluid oxytocin, life history of aggression, and personality disorder. Psychoneuroendocrinology 34:1567-73
Coccaro, Emil F; Lee, Royce J; Kavoussi, Richard J (2009) A double-blind, randomized, placebo-controlled trial of fluoxetine in patients with intermittent explosive disorder. J Clin Psychiatry 70:653-62

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