Additive and Interactive Effects of Attention-Deficit/Hyperactivity Disorder and Tic Disorder on Brain Connectivity.

ABSTRACT

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and persistent tic disorder (PTD) are two neurodevelopmental disorders that frequently co-occur. Contributions of each disorder to cognitive and behavioral deficits have been reported. In this paper, we tested 3 models of pathophysiology for the two disorders (additive, interactive, and phenotypic) using resting-state connectivity associated with each disorder separately and together. METHODS: Participants were 148 children (55 with ADHD only, 33 with ADHD and PTD, 27 with PTD only, and 33 healthy control subjects) at ages 8 to 12 years. Following diagnostic interviews and behavioral assessment, participants underwent a 128-channel electroencephalography recording. Resting-state, cortical source-level effective connectivity was analyzed across the 4 groups using a 2 × 2 factorial design with factors of ADHD (with/without) and PTD (with/without). RESULTS: ADHD diagnosis was the primary driver of cognitive and behavioral deficits, while deficits associated with PTD were primarily with thought problems and internalizing problems when compared with controls. Subadditive effects were observed in co-occurring ADHD+PTD for parent-rated behavioral problems and cognitive functions. Aberrant effective connectivity was primarily associated with ADHD, more specifically with lower posterior and occipital-frontal connectivity, while children with PTD exhibited greater left postcentral to precuneus connectivity. Weaker ADHD-related connectivity was associated with more severe behavioral problems, including internalizing behaviors, thought problems, and working memory deficits. CONCLUSIONS: Similar to general behavioral deficits, aberrant resting-state neural connectivity in pediatric ADHD and PTD combines additively in co-occurring cases. The findings of this study support ADHD as a focus of treatment in comorbid cases, given the driving role of ADHD in both behavioral and neurophysiological deficits.