Intermittent explosive disorder

# Overview
Intermittent explosive disorder (IED) is a behavioral disorder characterized by extreme expressions of anger, often to the point of uncontrollable rage, that are disproportionate to the situation at hand.  It is currently categorized in the Diagnostic and Statistical Manual of Mental Disorders as an impulse control disorder.  IED  belongs to the larger family of Axis I impulse control disorders listed in the DSM-IV-TR, along with kleptomania, pyromania, pathological gambling, and others.  Impulsive aggression is unpremeditated, and is defined by a disproportionate reaction to any provocation, real or perceived.  Some individuals have reported affective changes prior to an outburst (e.g., tension, mood changes, energy changes, etc.).
A 2006 study published by Harvard University researchers suggests that the disorder is considerably more prevalent than previously thought.  In a study of almost 10,000 individuals 18 years or older, lifetime episodes were reported at 7.3%, while 12-month occurrences were reported at 3.9%.  This suggests a mean lifetime occurrence of 43 instances, with an average of $1359 in property damage.
A 2005 study conducted in Rhode Island found the prevalence to be 6.3% (SE, +/- 0.7%) for lifetime DSM-IV IED in a study of 1300 patients under psychiatric evaluation. The national prevalence has not been established, and the disorder is considered to be relatively rare, due at least in part to the fact that an IED diagnosis is usually given only if all other possible disorders and syndromes are ruled out.  Prevalence is higher in men than in women.  The disorder itself is not easily characterized and often exhibits comorbidity with other mood disorders, particularly bipolar disorder.
In this same study, 27 subjects exhibiting DSM-IV IED were recruited and interviewed to describe their symptomology and episodic behaviors.  All subjects described outbursts as brief, lasting an average of 22 minutes  SD of 23 minutes. One-third of the subjects reported experiencing somatization prior to an episode, e.g. tingling, tremor, palpitations, chest tightness, head pressure, or hearing an echo. Over half of the subjects reported an alteration in their awareness during the episode, but none reported amnesia of the outburst.  Subjects generally reported an inability to resist the impulse to violence, and often reported a feeling of relief (88% reporting) or even pleasure (46% reporting) while committing the acts.  After the acts, many subjects reported feelings of remorse at their actions.  Remarkably, all 27 subjects reported their experiences with IED consistently.

# Pathophysiology
Impulsive behavior, and especially impulsive violence predisposition has been correlated to a low brain serotonin turnover rate, indicated by a low concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebral spinal fluid (CSF).  This substrate appears to have important neurochemical properties, acting on the suprachiasmatic nucleus in the hypothalamus, which is the target for serotonergic output from the dorsal and median raphe nuclei.  This site plays a role in the maintaining the circadian rhythm and regulation of glucose metabolism.  A putative hereditary component to low CSF 5-HIAA and concordantly possibly to impulsive violence has been proposed upon observation that sons of alcoholic fathers who exhibit violent behavior also exhibit exceptionally low CSF 5-HIAA.  Along with low CSF 5-HIAA concentration, vagal tone and increased insulin secretion has been observed in patients with confirmed DSM-IV IED.
Possible polymorphisms in the gene for tryptophan hydroxylase, which is responsible for the production of hydroxytryptophan, the precursor of serotonin.  Within violent subjects, a significant relationship was observed between CSF 5-HIAA concentration and specific polymorphism genotypes.  The phenotypes associated with these genotypes are extreme and it is hypothesized that these polymorphisms may only be significantly correlated to impulsive behavior.
Additionally, lesions in the orbital/medial prefrontal cortex and related areas appear to be correlated to impulsively violent behavior, although currently no study has pinned down a specific area involved in IED.  Research has shown, however, that damage in these areas, including the amygdale, increases the incidence of impulsive and aggressively violent behavior, and appears to decrease inhibition and ability to control emotion, as well as decreasing the ability to project consequences for their actions.  Subjects who exhibit lesions in these regions may also exhibit decreased glucose metabolism, and concordantly decreased brain function in the prefrontal cortex, the region associated with decision making and action planning.  More importantly is a reduced action in serotonergic neurons in this region as well as the amygdala.

# Differential Diagnosis
- Antisocial personality disorder
- Attention-deficit/hyperactivity disorder
- Autism spectrum disorder
- Borderline personality disorder
- Conduct disorder
- Delirium
- Disruptive mood dysregulation disorder
- Major neuro cognitive disorder and personality change due to another medical condition, aggressive type
- Oppositional defiant disorder
- Substance intoxication or substance withdrawal
- Alcohol
- Phencyclidine
- Cocaine and other stimulants
- Barbiturates

# Epidemiology and Demographics

## Prevalence
The one year prevalence of intermittent explosive disorder is 2,700 per 100,000 (2.7%) of the overall population

# Risk Factors
- Genetic predisposition
- History of physical and emotional trauma

# Diagnostic Criteria

## DSM-V Diagnostic Criteria for Intermittent Explosive Disorder

# Diagnosis & Treatment
The DSM-IV criteria for IED include: the occurrence of discrete episodes of failure to resist aggressive impulses that result in violent assault or destruction of property, the degree of aggressiveness expressed during an episode is grossly disproportionate to provocation or precipitating psychosocial stressor, and, as previously stated, diagnosis is made when other mental disorders that may cause violent outbursts (e.g., antisocial personality disorder, borderline personality disorder, attention deficit/hyperactivity disorder, etc.) have been ruled out.  Furthermore, the acts of aggression must not be due to a general medical condition, e.g., a head injury, Alzheimers disease, etc., or due to substance abuse or medication.  Diagnosis is made using a psychiatric interview to affective and behavioral symptoms to the criteria listed in the DSM-IV.
Treatment is achieved through both cognitive behavioral therapy and psychotropic medication regiments.  Therapy aids in helping the patient recognize the impulses in hopes of achieving a level of awareness and control of the outbursts, along with treating the emotional stress that accompanies these episodes.  Multiple drug regimens are frequently indicated for IED patients.  Tricyclic antidepressants and serotonin reuptake inhibitors (SRIs) such as fluoxetine, fluvoxamine, and sertraline appear to alleviate some pathopsychological symptoms; the reasons for such will be explained further in the subsequent section.  GABAergic mood stabilizers and anticonvulsive drugs such as gabapentin, lithium, carbamazepine, and divalproex seem to aid in controlling the incidence of outbursts.  Anxiolytics help alleviate tension and may help reduce explosive outbursts by increasing the provocative stimulus tolerance threshold, and are especially indicated in patients with comorbid obsessive-compulsive or other anxiety disorders.