Abstract: Although irritability is among the most common reasons that children and adolescents are brought for psychiatric care, there are few effective treatments. Developmentally sensitive pathophysiological models are needed to guide treatment development. In this review, the authors present a mechanistic model of irritability that integrates clinical and translational neuroscience research. Two complementary conceptualizations of pathological irritability are proposed: 1) aberrant emotional and behavioral responding to frustrative nonreward, mediated by reward-system dysfunction; and 2) aberrant approach responding to threat, mediated by threat-system dysfunction. The authors review the pathophysiological literature, including animal studies, as well as experimental psychology and clinical studies. Data suggest that, relative to healthy children, irritable children have deficient reward learning and elevated sensitivity to reward receipt and omission. These deficits are associated with dysfunction in the prefrontal cortex, striatum, and amygdala. Youths with irritability also show maladaptive orienting to, interpreting, and labeling of potential threats, associated with prefrontal cortical and amygdalar dysfunction. Abnormalities in reward and threat processing potentiate one another. Future work should test pathophysiological hypotheses and novel interventions targeting reward- and threat-related dysfunction to improve treatment for severe irritability in youths.
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The participant will recognize the role that aberrant reward and threat processing plays in pathological irritability.
This program is designed for all psychiatrists in clinical practice, residents in Graduate Medical Education programs, medical students interested in psychiatry, and other physicians who wish to advance their current knowledge of clinical medicine.
Estimated Time to Complete
Duration: 1 hour
Begin Date: June 1, 2017
End Date: May 31, 2019
How to Earn Credit
In order to earn CME credit, subscribers should read through the material presented in the article. After reading the article, complete the quiz and submit your evaluation and study hours (up to 1 AMA PRA Category 1 Credit™). A score of 60% or higher is required to receive credit.
The American Psychiatric Association (APA) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The APA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Faculty and Planner Disclosures
Title: Irritability in Youths: A Translational Model
Authors: Melissa A. Brotman, Ph.D., Katharina Kircanski, Ph.D., Argyris Stringaris, M.D., Ph.D., Daniel S. Pine, M.D., Ellen Leibenluft, M.D.
Affiliations: From the Emotion and Development Branch, NIMH, Bethesda, Md. (M.A.B., K.K., A.S., D.S.P., E.L.).
Disclosures: Dr. Stringaris has received funding from the Wellcome Trust and the U.K. National Institutes of Health Research, funds from University College London for a joint project with Johnson & Johnson, and royalties from Cambridge University Press and Oxford University Press. The other authors report no financial relationships with commercial interests.
Discussion of unapproved or investigational use of products*: No.
*APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by scientific literature and clinical experience.
Robert Freedman, M.D. (Editor-in-Chief, AJP); Susan K. Schultz, M.D. (Deputy Editor, AJP); Michael D. Roy (Editorial Director, AJP); Michael A. Pogachar (Online Content Manager, Journals).
Dr. Schultz has received research support from the Alzheimer’s Disease Cooperative Study for projects conducted in partnership with Toyama Chemical Company and in partnership with Eli Lilly and Company. Dr. Freedman, Mr. Roy, and Mr. Pogachar report no financial relationships with commercial interests.
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