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A tract profile study in adults with research-quality childhood diagnoses

White matter abnormalities associated with ADHD outcomes in adulthood

Subjects

Abstract

It remains unclear if previously reported structural abnormalities in children with ADHD are present in adulthood regardless of clinical outcome. In this study, we examined the extent to which focal—rather than diffuse—abnormalities in fiber collinearity of 18 major white matter tracts could distinguish 126 adults with rigorously diagnosed childhood ADHD (ADHD; mean age [SD] = 34.3 [3.6] years; F/M = 12/114) from 58 adults without ADHD histories (non-ADHD; mean age [SD] = 33.9 [4.1] years; F/M = 5/53) and if any of these abnormalities were greater for those with persisting ADHD symptomatology. To this end, a tract profile approach was used. After accounting for age, sex, handedness, and comorbidities, a MANCOVA revealed a main effect of group (ADHD < non-ADHD; F[18,155] = 2.1; p = 0.007) on fractional anisotropy (FA, a measure of fiber collinearity and/or integrity), in focal portions of white matter tracts involved in visuospatial processing and memory (i.e., anterior portion of the left inferior longitudinal fasciculus, and middle portion of the left and right cingulum angular bundle). Only abnormalities in the anterior portion of the left inferior longitudinal fasciculus distinguished probands with persisting versus desisting ADHD symptomatology, suggesting that abnormalities in the cingulum angular bundle might reflect “scarring” effects of childhood ADHD. To our knowledge, this is the first study using a tract profile approach to identify focal or widespread structural abnormalities in adults with ADHD rigorously diagnosed in childhood.

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Fig. 1: A–B Legend.

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Acknowledgements

The present study was supported by the National Institute of Mental Health grant MH101096 (MPIs: Molina and Ladouceur), by the National Institute on Alcohol Abuse and Alcoholism grant AA011873 (PI: Molina), and by the National Institute on Drug Abuse grant DA012414 (PI: Pelham). These funding agencies were not involved in the design or conduct of the study, the collection, management, analysis, or interpretation of the data, or the preparation, review, or approval of the manuscript.

We acknowledge Drs. A. Yendiki (TRACULA’s developer) and E. Caruyer (optimization of the gradient schema) for their scientific contributions to this work. We also acknowledge our research participants for their participation into this study.

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AV, CDL, and BSGM contributed to the conception or design of the work. AV, RAL, TKW, JPLS, and EMG contributed to the data acquisition and data analysis. AV, NPJ, HMJ, WEP, CDL, and BSGM contributed to the interpretation of data. AV contributed to drafting the manuscript. NPJ, HMJ, CDL, and BSGM reviewed the manuscript critically for important intellectual content. All authors gave final approval of the version to be submitted for publication and are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to A. Versace.

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Versace, A., Jones, N.P., Joseph, H.M. et al. White matter abnormalities associated with ADHD outcomes in adulthood. Mol Psychiatry 26, 6655–6665 (2021). https://doi.org/10.1038/s41380-021-01153-7

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