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Recent controversy concerning the diagnosis of mania in children has focused attention on how little is known about how to assess irritability in a systematic way, and about its diagnostic associations. For example, subtyping irritability according to course (chronic vs. episodic), precipitants, and family history may facilitate the identification of psychopathology and the study of pathophysiology. While normative and pathologic irritability can be differentiated reliably, the validity of the distinction is unclear. In addition, there is a need for scales designed to measure the severity of irritability in children with mood and anxiety disorders. In order to facilitate research, we propose a definition of irritability from the perspective of affective neuroscience. Because reactive aggression may be a helpful animal model for irritability, we review the neural circuitry mediating this behavior. Behavioral paradigms that evoke frustration, as well as those that assess the ability to inhibit a prepotent motor response, maintain attentional focus, execute response reversal, recognize angry faces, and regulate emotional responses, may be useful in the study of irritability. Examples of such paradigms are described, and the pharmacology of irritability is reviewed briefly.<\/jats:p>","DOI":"10.1196\/annals.1301.022","type":"journal-article","created":{"date-parts":[[2004,3,2]],"date-time":"2004-03-02T22:33:27Z","timestamp":1078266807000},"page":"201-218","source":"Crossref","is-referenced-by-count":120,"title":["Irritability in Pediatric Mania and Other Childhood Psychopathology"],"prefix":"10.1111","volume":"1008","author":[{"given":"ELLEN","family":"LEIBENLUFT","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R JAMES R.","family":"BLAIR","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DENNIS S.","family":"CHARNEY","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DANIEL S.","family":"PINE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,24]]},"reference":[{"key":"e_1_2_8_2_2","unstructured":"American Psychiatric Association. 2000. 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