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Neural Mechanisms of Irritability/Anxiety in Youth

JAMA Psychiatry; ePub 2018 Apr 6; Kircanski, et al

During orientation away from threat, only irritability was associated with neural activity, whereas only anxiety was associated with amygdala connectivity, in a recent study that examined the unique and shared variances of pediatric irritability and anxiety symptoms and to determine neural correlates of these differentiated phenotypes during threat orienting. This cross-sectional, functional, magnetic resonance imaging study, evaluated youth aged 8 to 18 years spanning multiple diagnostic categories (141 youth with disruptive mood dysregulation disorder, anxiety disorder, and/or attention-deficit/hyperactivity disorder, and 56 healthy controls). Researchers found:

  • Among 197 participants included in the final analysis, the mean (SD) age was 13.1 (2.7) years, and 91 (46.2%) were female.
  • The best-fit bifactor model included unique factors of parent-reported irritability, youth-reported irritability, and anxiety, as well as a common factor of negative affectivity.
  • When the task required attention away from threat, higher parent-reported irritability was associated with increased activity in the insula, caudate, dorsolateral, and ventrolateral prefrontal cortex, and inferior parietal lobule.
  • In contrast, higher anxiety was associated with decreased amygdala connectivity to the cingulate, thalamus, and precentral gyrus.


Kircanski K, White LK, Tseng W-L, et al. A latent variable approach to differentiating neural mechanisms of irritability and anxiety in youth. [Published online ahead of print April 6, 2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.0468.