Intermittent Explosive Disorder (IED), in DSM-IV (American Psychiatric Association, 1994), is characterized by recurrent episodes of serious aggressive outbursts that are out of proportion to psychosocial stressors/provocation and that are not better accounted for by another mental disorder, co-morbid medical conditions, or the physiological effects of a pharmacological agent. Over the past several years, efforts to refine the DSM-IV IED criteria have resulted in IED Research Criteria that operationalize the type and frequency of aggression and the degree to which the aggressive behavior impacts on psychosocial function (Coccaro et al., 1998 and Coccaro et al., 2004). Current IED Research Criteria require the frequency of aggressive behavior to be at least three episodes of serious assault (or destruction of property) in a one-year period, or at least two outbursts per week, for no less than one month, involving verbal aggression or aggression against objects (Coccaro et al., 2004). These IED Research Criteria also require criteria-meeting aggressive episodes to be impulsive, as opposed to premeditated, in nature and require the aggressive behavior to be associated with significant psychosocial impairment and/or distress.
Using either DSM-IV or IED Research Criteria, recent epidemiologic data suggests that from about 4 to 7% of the general population in the United States (Coccaro et al., 2004 and Kessler et al., 2006) and about 2–10% of the population of other countries (Bromet et al., 2005 and Fincham et al., 2009) have IED over the course of their lifetime. About 70% of these individuals have at least three aggressive outbursts per year and average more than twenty-seven aggressive outbursts per year (Kessler et al., 2006). While DSM-IV does not formally define relevant aggressive outbursts as impulsive, all the epidemiologic studies, to date, required the aggressive acts to occur “all of a sudden” and, thus, be impulsive in nature.
Data from twin, adoption, and family studies suggest genetic influence on impulsivity and aggression (Bergeman and Seroczynski, 1998 and Seroczynski et al., 1999). In adults, heritability estimates ranging from 44% to 72% have been reported (Rushton et al., 1986, Tellegen et al., 1988, Cates et al., 1993, Coccaro et al., 1993 and Coccaro et al., 1997a) and a meta-analysis study confirmed a substantial genetic influence for aggression (Miles and Carey, 1997). The later study found that heritability estimates were most pronounced for aggression measures reflecting anger and hostility and/or anger, impulsiveness and irritability (Rushton et al., 1986, Tellegen et al., 1988, Cates et al., 1993, Coccaro et al., 1993 and Coccaro et al., 1997a). These are the same phenomena associated with the clinical profile of IED and, thus, it is likely that IED is heritable and runs in families.
While there are no twin or adoption studies of IED, existing family history data suggests that IED or IED-type behavior may be familial. The first-degree relatives of patients with histories of violent behavior have a high incidence of violent behavior (Bach-y-Rita et al., 1971 and Maletsky, 1973). An increased frequency of first-degree relatives with history of temper outbursts and a strong trend for familial aggregation of IED (defined as the first two DSM-III criteria for IED) was reported in psychiatric patients with history of temper outbursts compared to other patients (Mattes and Fink, 1987). While neither a blinded nor controlled study, McElroy et al. (1998) reported that 32% of first-degree relatives of IED probands met criteria for IED.
In this paper we report the results of a blinded, controlled, family history study of IED by research criteria (IED-IR) using reliable and comprehensive assessments of psychopathology and DSM-IV disorders. IED-IR criteria include the essence of DSM-IV IED criteria but are more precise and valid in terms of analog behavioral studies (McCloskey et al., 2005) or serotonergic biomarkers (Coccaro et al., 2010a and Coccaro et al., 2010b). We hypothesized that there would be a significantly elevated morbid risk of IED-IR in first-degree relatives of IED-IR Probands compared to Control Probands was found. We further hypothesized that Familial IED-IR would not be affected by co-morbidity in IED-IR probands and that co-morbidity of Non-IED disorders in relatives would also not be affected by presence of IED-IR in those relatives.
