Neural correlates of Irritability: A novel cross-diagnosis dimensional approach

FARE Award Winner

Authors

• W-L Tseng
• CM Deveney
• E Moroney
• L Machlin
• KE Towbin
• DS Pine
• MA Brotman
• E Leibenluft

Abstract

Background: Irritability is a core feature of disruptive mood dysregulation disorder (DMDD), yet it cuts across many other pediatric disorders, making it suitable to be studied under the Research Domain Criteria (RDoC) framework. We utilized a frustrating fMRI task to examine the neural correlates of irritability using two complementary approaches. First, we examined associations between brain activation and a dimensional measure of irritability. Next, we employed a categorical approach to compare activation across four diagnostic groups: DMDD, attention-deficit/hyperactivity disorder (ADHD), anxiety disorder (ANX), and healthy volunteers (HV). Methods: 19 DMDD, 16 ADHD, 24 ANX, and 31 HV youths (mean age=12.8 years; 53.3% girls) completed an affective Posner task while fMRI data were acquired. Frustration was elicited by providing participants rigged feedback. Parent report of the Affective Reactivity Index scale was used as a dimensional measure of irritability. Results: Groups differed on parent-reported irritability (pADHD=ANX>HV). Dimensional analyses revealed that higher irritability was related to decreased activation in parahippocampal gyrus during positive (r=-.24, p=.02) but not rigged feedback (r=.08, p=.46). Whole-brain 4(Group: DMDD, ADHD, ANX, HV)×2(Condition: Rigged vs. Positive Feedback) ANOVAs revealed within-group differences only in DMDD in superior temporal gyrus and parahippocampal gyrus. Generally consistent with the dimensional findings, DMDD youth showed increased activation in these regions when receiving rigged vs. positive feedback (ps≤.003). Conclusions: Preliminary findings in this first fMRI study on DMDD suggest that abnormal neural activation in the parahippocampal gyrus and superior temporal gyrus, regions implicated in emotion regulation and social perception, may mediate irritability in youth.

Scientific Focus Area: Neuroscience

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