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Associations between ADHD symptom remission and white matter microstructure: a longitudinal analysis

By Anne E. M. Leenders, Christienne G. Damatac, Sourena Soheili-Nezhad, Roselyne J. M. Chauvin, Maarten J. J. Mennes, Marcel P. Zwiers, Daan van Rooij, Sophie E. A. Akkermans, Jilly Naaijen, Barbara Franke, Jan K. Buitelaar, Christian F Beckmann, Emma Sprooten

Posted 25 Sep 2020
bioRxiv DOI: 10.1101/2020.09.24.311654

Objective Attention-deficit hyperactivity disorder (ADHD) is associated with white matter (WM) microstructure. Our objective was to investigate how WM microstructure is longitudinally related to symptom remission in adolescents and young adults with ADHD. Method We obtained diffusion-weighted imaging (DWI) data from 99 participants at two time points (mean age baseline: 16.91 years, mean age follow-up: 20.57 years). We used voxel-wise Tract-Based Spatial Statistics (TBSS) with permutation-based inference to investigate associations of inattention (IA) and hyperactivity-impulsivity (HI) symptom change with fractional anisotropy (FA) at baseline, follow-up, and change difference between time points. Results Remission of combined HI and IA symptoms was significantly associated with reduced FA at follow-up in the left superior longitudinal fasciculus and the left corticospinal tract (CST) ( P FWE =0.038 and P FWE =0.044, respectively), mainly driven by an association between HI remission and follow-up CST FA ( P FWE =0.049). There was no significant association of combined symptom remission with FA at baseline or with changes in FA between the two assessments. Conclusion In this longitudinal DWI study of ADHD using dimensional symptom scores, we show that greater symptom remission is associated with lower follow-up FA in specific WM tracts. Altered FA thus may appear to follow, rather than precede, changes in symptom remission. Our findings indicate divergent WM developmental trajectories between individuals with persistent and remittent ADHD, and support the role of prefrontal and sensorimotor tracts in the remission of ADHD. ### Competing Interest Statement A.E.M.L. reports no biomedical financial interests or potential conflicts of interest. C.G.D. reports no biomedical financial interests or potential conflicts of interest. S.S.N. reports no biomedical financial interests or potential conflicts of interest. R.J.M.C. reports no biomedical financial interests or potential conflicts of interest. M.J.J.M. reports no biomedical financial interests or potential conflicts of interest. M.P.Z. reports no biomedical financial interests or potential conflicts of interest. D.v.R reports no biomedical financial interests or potential conflicts of interest. S.E.A.A. reports no biomedical financial interests or potential conflicts of interest. J.N. is funded by a personal Veni grant from the Innovation Program of the Netherlands Organization for Scientific Research (NWO; grant VI.Veni.194.032). B.F. has received support from the European Community Horizon 2020 Programme (H2020/2014 to 2020) under grant agreement n 667302 (CoCA) and has received educational speaking fees from Medice. J.K.B. has been consultant to/member of advisory board of and/or speaker for Janssen Cilag BV, Eli Lilly, Bristol-Myer Squibb, Shering Plough, UCB, Shire, Novartis and Servier. He is not an employee of any of these companies, nor a stock shareholder of any of these companies. C.F.B. reports no biomedical financial interests or potential conflicts of interest. E.S. is funded by a Hypatia Fellowship (Radboudumc) and a NARSAD Young Investigator Grant (Brain and Behavior Research Foundation, ID: 25034).

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