Intermittent explosive disorder (sometimes abbreviated as IED) is a behavioral disorder characterized by explosive outbursts of anger and/or violence, often to the point of rage, that are disproportionate to the situation at hand (e.g., impulsive shouting, screaming or excessive reprimanding triggered by relatively inconsequential events). Impulsive aggression is not premeditated, and is defined by a disproportionate reaction to any provocation, real or perceived. Some individuals have reported affective changes prior to an outburst, such as tension, mood changes, energy changes, etc. The disorder is currently categorized in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) under the "Disruptive, Impulse-Control, and Conduct Disorders" category. The disorder itself is not easily characterized and often exhibits comorbidity with other mood disorders, particularly bipolar disorder. Individuals diagnosed with IED report their outbursts as being brief (lasting less than an hour), with a variety of bodily symptoms (sweating, stuttering, chest tightness, twitching, palpitations) reported by a third of one sample. Aggressive acts are frequently reported to be accompanied by a sensation of relief and in some cases pleasure, but often followed by later remorse. Pathophysiology Impulsive behavior, and especially impulsive violence predisposition, have been correlated to a low brain serotonin turnover rate, indicated by a low concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). This substrate appears to act on the suprachiasmatic nucleus in the hypothalamus, which is the target for serotonergic output from the dorsal and median raphe nuclei playing a role in maintaining the circadian rhythm and regulation of blood sugar. A tendency towards low 5-HIAA may be hereditary. A putative hereditary component to low CSF 5-HIAA and concordantly possibly to impulsive violence has been proposed. Other traits that correlate with IED are low vagal tone and increased insulin secretion. A suggested explanation for IED is a polymorphism of the gene for tryptophan hydroxylase, which produces a serotonin precursor; this genotype is found more commonly in individuals with impulsive behavior. IED may also be associated with damage or lesions in the prefrontal cortex, with damage to these areas, including the amygdala and hippocampus, increasing the incidences of impulsive and aggressive behavior and the inability to predict the outcomes of an individual's own actions. Lesions in these areas are also associated with improper blood sugar control, leading to decreased brain function in these areas, which are associated with planning and decision making. A national sample in the United States estimated that