Irritability and Mental Retardation.

Irritability is a persistent and unpleasant mood state characterized by low frustration tolerance, hostility, impulsivity, and aggression. It may be a normal response to stress or reflect significant central nervous system (CNS) dysfuntion, eg, dementia. There are 15 Diagnostic and Statistical Manual-IV-defined disorders in which irritability is either a diagnostic or associated feature. Evidence from animal and human studies indicates that pathological irritability reflects limbic system dysfunction with a central dysregulation of serotonergic inhibition of dopaminergic activity. In mentally retarded person, irritability may be a mediator of aggression and self-injury associated with psychiatric disorders such as depression and mania. In addition, it has been reported in persons with severe and profound disabilities who have had significant CNS disease such as congenital rubella. There is evidence that an "organic irritability syndrom" exists which is characterized by persistent irritable mood in conjunction with hyperactivity and/or disrupted sleep. Patients with organic irritability lack the typical hyposomnia and pressured verbalizations associated with mania. When irritability is associated with a drug-responsive psychiatric illness, it usually remits with treatment directed at the underlying syndrome. When it is associated with CNS dysfunction in the absence of a classic psychiatric disorder, dopamine receptor antagonism and/or CNS 5-hydroxytryptamine (5-HT) activity are the typical strategies. Carbamazepine, lithium, serotonin reuptake inhibitors, and typical and atypical neuroleptics have been the most commonly used drugs and all been reported to be effective in moderating irritability. Unfortunately, there are few controlled trials to aid in treatment selecton.