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White Matter Microstructure in Pediatric Bipolar Disorder and Disruptive Mood Dysregulation Disorder

https://doi.org/10.1016/j.jaac.2019.05.035Get rights and content

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.

Section snippets

Participants

We collected data on 118 youths (aged 11–21 years) diagnosed with either DMDD (n = 44) or BD (n = 36; n = 22 BD I, n = 14 BD II) and healthy volunteers (HV, n = 38). The three subgroups were comparable regarding sex, age, IQ and socioeconomic status. BD youth were more likely than DMDD youth to receive mood stabilizing medication (antiepileptics, lithium) and benzodiazepines, reflected in a higher medication load score17 (Table 1), which was covaried in the DTI analyses. Participants over age

Fractional Anisotropy

The omnibus ANCOVA showed a main effect of diagnosis in a large cluster centered at the anterior CC (x = −10, y = 25, z = 15, 5997 voxels, pmin = 0.0008) that extended along the CC and included fibers of the ATR, CST, IFOF, SLF, and UF. Post hoc comparison showed lower FA values in BD vs DMDD in the superior corona radiata/ CST (x = −28, y = −17, z = 19, 719 voxels, pmin = 0.004), splenium of the CC (x = −2, y = −36, z = 20, 352 voxels, pmin = 0.013), and SLF (x = −33, y = −43, z = 22, 128

Discussion

The present study aimed (1) to investigate aberrancies in WM microstructure in DMDD compared to BD and HV youth; (2) to determine whether abnormalities in WM microstructure identified in the first analysis relate to symptoms of irritability; and (3) to test whether diagnosis can be predicted based on WM microstructure. Regarding the first goal, we observed lower FA in the CST in BD vs DMDD; lower FA values in the anterior CC that were driven by reduced AD values in DMDD vs HV; and widespread

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    • Cited by (0)

    Drs. Linke and Adleman contributed equally to this work.

    This research was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH) (ZIA: MH002778-18; ClinicalTrials.gov identifier: NCT00025935, and ZIA: MH002786-16; ClinicalTrials.gov identifier: NCT00006177).

    Disclosure: Drs. Linke, Adleman, Sarlls, Towbin, Pine, Leibenluft, Brotman, Mr. Ross, and Mss. Perlstein and Frank have reported no biomedical financial interests or potential conflicts of interest.

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    Published by Elsevier Inc. on behalf of the American Academy of Child and Adolescent Psychiatry.