The primary specific aim of this study is to test the hypothesis that Intermittent Explosive Disorder (IED) is familial. IED is a disorder characterized by recurrent, sudden eruptions of aggressive behavior not due to psychosis, substance intoxication, or other frank organic causes. Accordingly, IED is the categorical expression of recurrent, problematic, impulsive aggressive behavior. While it is thought that the personality dimension of impulsive aggression is familial (and possibly under substantial genetic influence), there is a paucity of systematically collected data to support this hypothesis with regard to clinically significant impulsive aggressive behavior. A family history study by the PI demonstrates that IED (by research criteria) aggregates in first degree relatives of IED+ Probands. Aggregation of IED in these first degree relatives was not accounted for by co-morbidity of other Axis I or II conditions in the IED+ Probands. While aggregation of other Axis I disorders was also noted in the first degree relatives of IED+ Probands (e.g., major depression, alcohol/drug use disorders, etc.), the risk of IED in relatives was not affected by the risk of these other disorders in the relatives. That is, IED was transmitted independently of these other Axis I disorders. The formal specific aims of this study are as follows: a) to compare the familiality of IED, and of dimensional measures of aggression, in first degree relatives of IED+ Probands (n = 80), in first-degree relatives of Psychiatric Control Probands (n = 80) and in first-degree relatives of Outpatient Surgical Control Probands (n = 80) using the direct Family Study Method; b) to compare the familiality of Major Depression and Alcohol/Drug Use Disorders in first degree relatives of Probands meeting Research Criteria for IED (by research criteria) and in relatives of the two Control groups; and, c) to explore phenomenologic and biologic correlates of familial IED in probands and in family members of IED probands (i.e., relatives of IED probands with and without IED).

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Special Emphasis Panel (ZRG1-SNEM-2 (01))
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Breiling, James P
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University of Chicago
Schools of Medicine
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Rynar, Lauren; Coccaro, Emil F (2018) Psychosocial impairment in DSM-5 intermittent explosive disorder. Psychiatry Res 264:91-95
Montalvo-Ortiz, Janitza L; Zhang, Huiping; Chen, Chao et al. (2018) Genome-Wide DNA Methylation Changes Associated with Intermittent Explosive Disorder: A Gene-Based Functional Enrichment Analysis. Int J Neuropsychopharmacol 21:12-20
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; 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

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