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J Am Acad Child Adolesc Psychiatry. 2018 May;57(5):336-342.e6. doi: 10.1016/j.jaac.2018.02.010. Epub 2018 Mar 16.

Irritability Trajectories, Cortical Thickness, and Clinical Outcomes in a Sample Enriched for Preschool Depression.

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New York State Psychiatric Institute and College of Physicians and Surgeons, Columbia University, New York. Electronic address:
Emotion and Development Branch, National Institute of Mental Health (NIMH), Bethesda, MD.
Washington University School of Medicine, St. Louis, MO.



Cross-sectional, longitudinal, and genetic associations exist between irritability and depression. Prior studies have examined developmental trajectories of irritability, clinical outcomes, and associations with child and familial depression. However, studies have not integrated neurobiological measures. The present study examined developmental trajectories of irritability, clinical outcomes, and cortical structure among preschoolers oversampled for depressive symptoms.


Beginning at 3 to 5 years old, a sample of 271 children enriched for early depressive symptoms were assessed longitudinally by clinical interview. Latent class mixture models identified trajectories of irritability severity. Risk factors, clinical outcomes, and cortical thickness were compared across trajectory classes. Cortical thickness measures were extracted from 3 waves of magnetic resonance imaging at 7 to 12 years of age.


Three trajectory classes were identified among these youth: 53.50% of children exhibited elevated irritability during preschool that decreased longitudinally, 30.26% exhibited consistently low irritability, and 16.24% exhibited consistently elevated irritability. Compared with other classes, the elevated irritability class exhibited higher rates of maternal depression, early life adversity, later psychiatric diagnoses, and functional impairment. Further, elevated baseline irritability predicted later depression beyond adversity and personal and maternal depression history. The elevated irritability class exhibited a thicker cortex in the left superior frontal and temporal gyri and the right inferior parietal lobule.


Irritability manifested with specific developmental trajectories in this sample enriched for early depression. Persistently elevated irritability predicted poor psychiatric outcomes, higher risk for later depression, and decreased overall function later in development. Greater frontal, temporal, and parietal cortical thickness also was found, providing neural correlates of this risk trajectory.


cortical thickness; development; irritability; latent trajectory; magnetic resonance imaging

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