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Understanding the Brain Mechanisms of Irritability in Youth

Findings may inform the development of new treatments for severe irritability

Science Update

In an NIMH-funded study, researchers have identified differences in how the brains of irritable youth react to frustration. The findings , published in The American Journal of Psychiatry, could provide new paths for developing treatments for children and adolescents with severe irritability.

Whether it’s having to wake up earlier than usual or being asked to turn off a favorite TV show, all children can become irritable sometimes. However, some children are more irritable than others, with an increased tendency to experience anger and frustration in comparison with their peers. Children who have severe, chronic irritability can experience significant problems including at home, at school, and with peers. They also tend to have high rates of health care service use, hospitalization, and school suspension and are more likely to develop anxiety and depressive disorders.

A better understanding of the physiological processes that underlie irritability is critical to guide the development of therapies for this impairing yet common problem. Researchers, including those from the NIMH’s Section on Mood Dysregulation and Neuroscience, directed by Dr. Ellen Leibenluft, M.D., used functional magnetic resonance imaging (fMRI) to measure the brain activity of 195 youths (aged 8-18 years with varying levels of irritability) as they played a computerized attention game. The game was designed to mimic the type of frustration children sometimes experience in their daily lives when rewards are withheld, and they are asked to adjust their behaviors—for example, when a child is asked to stop playing a video game and start their homework. The participants received feedback (some of which was frustrating) on their performance.

“Our goal was to understand how children’s brains react to frustrating events, and how this differs between irritable and non-irritable kids. In particular, some kids may have difficulty continuing to pay attention to a task when they feel frustrated, and this could make it hard for them to function well both at home and in school,” explained Wan-Ling Tseng, Ph.D., a postdoctoral researcher at the NIMH and lead author of the study.

The researchers found that following frustration, children with greater levels of irritability showed more neural activation in the frontal-striatal region of the brain involved in regulating attention, inhibition, impulse control, and processing rewards and feedback.

“We think that this may be because irritable kids’ brains have to ‘work harder’ to be able to stay on task when frustrated. This is particularly true for younger children with irritability,” said Dr. Tseng.

Results were similar for both boys and girls and were the same regardless of whether children were taking medication for mood or attention disorders. The fact that medication had no impact on brain activation during frustration suggests current medication used to treat mental illnesses such as disruptive mood dysregulation disorder (DMDD) and attention-deficit/hyperactivity disorder (ADHD)—both of which often present with symptoms of severe irritability—may not target the neural circuits relating to irritability and frustration.  

These findings suggest that novel treatments are needed for irritability.  Dr. Tseng added, “intervention efforts may need to include strategies that help irritable children cope with the negative emotions and arousal caused by frustration. Then the children will be better able to flexibly shift their attention to stay focused on the task at hand.”


Tseng, W., Deveney, C., Stoddard, J., Kircanski, K., Frackman, A., Yi, J., Hsu, D., … Leibenluft, E. (in press). Bain mechanisms of attention orienting following frustration: Associations with irritability and age in youth . The American Journal of Psychiatry


ZIA-MH002778 , ZIA-MH002781 , ZIA-MH002786 

Clinical Trials

NCT00006177 , NCT00018057 , NCT00025935