Abstract
OBJECTIVE: Disruptive mood dysregulation disorder (DMDD) codifies severe, chronic irritability. Youths with bipolar disorder (BD) also present with irritability, but with an episodic course. To date, it is not clear whether aberrant white matter microstructure-a well-replicated finding in BD-can be observed in DMDD and relates to symptoms of irritability. METHOD: We acquired diffusion tensor imaging data from 118 participants (BD = 36, DMDD = 44, healthy volunteers (HV = 38). Images of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were processed with tract-based spatial statistics controlling for age and sex. The data were also used to train Gaussian process classifiers to predict diagnostic group. RESULTS: In BD vs DMDD, FA in the corticospinal tract was reduced. In DMDD vs HV, reductions in FA and AD were confined to the anterior corpus callosum. In BD vs HV, widespread reductions in FA and increased RD were observed. FA in the anterior corpus callosum and corticospinal tract was negatively associated with irritability. The Gaussian process classifier could not discriminate between BD and DMDD, but achieved 68% accuracy in predicting DMDD vs HV and 75% accuracy in predicting BD vs HV. CONCLUSION: Aberrant white matter microstructure was associated with both categorical diagnosis and the dimension of irritability. Alterations in DMDD were regionally discrete and related to reduced AD. In BD, we observed widespread increases in RD, supporting the hypothesis of altered myelination in BD. These findings will contribute to the pathophysiological understanding of DMDD and its differentiation from BD. CLINICAL TRIAL REGISTRATION INFORMATION: Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder; https://clinicaltrials.gov/; NCT00025935; Child & Adolescent Bipolar Disorder Brain Imaging and Treatment Study; https://clinicaltrials.gov/; NCT00006177.