Why Am I Irritable?

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Irritability is defined as having a higher tendency to experience anger in response to frustration. In the field of child psychiatry, the symptom of irritability appears in multiple disorders, including autism, ADHD, anxiety disorders, depressive disorders, and conduct disorders. Targeting the neural mechanisms of irritability, something relatively unclear and unexplored, raises the opportunity to better understand the pathophysiology of these various youth disorders.

A study conducted by the Yale School of Medicine in conjunction with the National Institutes of Health (NIH) sought to analyze the functional connectivity between brain networks when a person was irritated. Functional connectivity measures the statistical relationship and dependence between two spatially independent regions of the brain. The study used functional MRI scans of sixty-nine youths who had to complete frustrating and non-frustrating cognitive flexibility tasks. With the aid of a machine learning tool called connectome-based predictive modeling, the study used spatiotemporal patterns from the brain activity data in order to predict differences in irritability behavior. 

The study identified 266 edges that measured the functional connectivity between nodes and predicted irritability in the study subjects. Many of the edges were found in the left cerebellum, left parietal region, motor-sensory cortex, and right thalamus. “One of the most important [edges] is the motor network to the frontal parietal network,” said Dustin Scheinost, a professor at the Yale School of Medicine and a member of the team conducting the study. 

These results indicate that youths may experience a larger activation of the motor and frontal parietal network during irritability. This study expands our prior knowledge on how functional connectivity, which is affected by both genetics and the environment, can help predict the differences in irritability in youth.


Scheinost, D., Dadashkarimi, J., Finn, E.S. et al. Functional connectivity during frustration: a preliminary study of predictive modeling of irritability in youth. Neuropsychopharmacol. (2021).