Irritability in Youths: A Translational Model.

Area of Science:

• Neuroscience
• Psychiatry
• Developmental Psychology

Background:

• Irritability is a common reason for psychiatric care in youth, yet effective treatments are scarce.
• Developmentally sensitive pathophysiological models are needed to guide the development of novel interventions.
• Existing research highlights the need for integrated clinical and translational neuroscience approaches.

Purpose of the Study:

• To present a mechanistic model of pathological irritability in youth.
• To integrate clinical and translational neuroscience research for understanding irritability.
• To propose two complementary conceptualizations of irritability based on reward and threat system dysfunction.

Main Methods:

• Review of pathophysiological literature, including animal, experimental psychology, and clinical studies.
• Integration of data from neuroscience research to form a mechanistic model.
• Analysis of reward and threat processing in irritable youth compared to healthy controls.

Main Results:

• Irritable youth exhibit deficient reward learning and heightened sensitivity to reward receipt and omission.
• These deficits are linked to dysfunction in the prefrontal cortex, striatum, and amygdala.
• Maladaptive threat processing, including orienting and interpretation, is associated with prefrontal cortical and amygdalar dysfunction.

Conclusions:

• Pathological irritability involves aberrant responding to frustrative nonreward (reward system dysfunction) and threat (threat system dysfunction).
• Abnormalities in reward and threat processing appear to potentiate each other.
• Future research should test these pathophysiological hypotheses and develop targeted interventions for severe irritability in youth.