¹Tri-Service General Hospital, National Defense Medical University, Department of Psychiatry, Taipei, Taiwan

Background: Disruptive mood dysregulation disorder (DMDD) is impairing among children and adolescents, and is associated with long-term negative psychiatric outcomes, including unipolar depression and anxiety. One of the main characteristics of DMDD is chronic irritability, a proneness to extraordinary emotional reactions during frustrating condition. Previous research found that children with DMDD showed aberrant activity in brain regions implicated in attention, emotion, and reward processing as the response to frustration.

Aims & Objectives: To date, there is limited information on resting-state functional connectivity of children with DMDD after frustration. In view of the high rate of comorbidity with ADHD among children with DMDD, this study aimed to explore the neurophysiological mechanisms of irritability by comparing the functional connectivity between children with ADHD only and those with overlap of DMDD and ADHD.

Method: We acquired resting-state imaging data from two groups of children (23 with DMDD and ADHD, and 22 with ADHD only). The scanning was performed under non-frustrating and frustrating conditions, which evoked by a modified affective Posner task. Emotional and behavioral symptoms were measured by SNAP-IV, CBCL, and Beck Youth Inventories - Second Edition. Group-level analysis of each connectivity map was done by analysis of covariance (ANCOVA) using 3dMVM with main factors of group (diagnosis), condition (frustration), and covariates sex, age, and FSIQ.

Results: Seed regions of interest were the bilateral amygdala, posterior cingulate, and nucleus accumbens, defined using the TT_Daemon atlas. We found the significant between-group difference by the effects of frustration in functional connectivity between the right amygdala and the right inferior semi-lunar lobule. The hyperconnectivity among DMDD and ADHD vs. ADHD only was correlated with symptoms of irritability, angry, oppositional defiant behaviors, aggression, and disruptive behaviors.

Discussion & Conclusions: Our findings indicate that functional connectivity under frustration is atypically increased in DMDD. Disturbed cerebellar input to the key region for processing fearful and threatening stimuli may contribute to irritability and aggression in DMDD.