Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury.
Biol Psychiatry. 2019 Mar 01; 85(5):408-416.BP

Abstract

BACKGROUND

Attention-deficit/hyperactivity disorder (ADHD) is a major sequela of traumatic brain injury (TBI) in youths. The objective of this study was to examine whether ADHD symptoms are differentially associated with genetic risk and brain structure in youths with and without a history of TBI.

METHODS

Medical history, ADHD symptoms, genetic data, and neuroimaging data were obtained from a community sample of youths. ADHD symptom severity was compared between those with and without TBI (TBI n = 418, no TBI n = 3193). The relationship of TBI history, genetic vulnerability, brain structure, and ADHD symptoms was examined by assessing 1) ADHD polygenic score (discovery sample ADHD n = 19,099, control sample n = 34,194), 2) basal ganglia volumes, and 3) fractional anisotropy in the corpus callosum and corona radiata.

RESULTS

Youths with TBI reported greater ADHD symptom severity compared with those without TBI. Polygenic score was positively associated with ADHD symptoms in youths without TBI but not in youths with TBI. The negative association between the caudate volume and ADHD symptoms was not moderated by a history of TBI. However, the relationship between ADHD symptoms and structure of the genu of the corpus callosum was negative in youths with TBI and positive in youths without TBI.

CONCLUSIONS

The identification of distinct ADHD etiology in youths with TBI provides neurobiological insight into the clinical heterogeneity in the disorder. Results indicate that genetic predisposition to ADHD does not increase the risk for ADHD symptoms associated with TBI. ADHD symptoms associated with TBI may be a result of a mechanical insult rather than neurodevelopmental factors.

Links

PMC Free PDF

Authors+Show Affiliations

Stojanovski S

Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.

Felsky D

Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

Viviano JD

Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Shahab S

Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Bangali R

Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Burton CL

Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada.

Devenyi GA

Cerebral Imaging Centre, Douglas Institute, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

O'Donnell LJ

Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Szatmari P

Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Chakravarty MM

Cerebral Imaging Centre, Douglas Institute, Montreal, Quebec, Canada; Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

Ameis S

Schachar R

Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Voineskos AN

Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Wheeler AL

Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada. Electronic address: anne.wheeler@sickkids.ca.

MeSH

AdolescentAnisotropyAttention Deficit Disorder with HyperactivityBasal GangliaBrain ConcussionCase-Control StudiesChildCorpus CallosumDiffusion Tensor ImagingFemaleHumansMaleMultifactorial InheritanceNeuroimagingSeverity of Illness IndexWhite MatterYoung Adult

Pub Type(s)

Journal Article

Research Support, N.I.H., Extramural

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30119875

Citation

Stojanovski, Sonja, et al. "Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury." Biological Psychiatry, vol. 85, no. 5, 2019, pp. 408-416.

Stojanovski S, Felsky D, Viviano JD, et al. Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury. Biol Psychiatry. 2019;85(5):408-416.

Stojanovski, S., Felsky, D., Viviano, J. D., Shahab, S., Bangali, R., Burton, C. L., Devenyi, G. A., O'Donnell, L. J., Szatmari, P., Chakravarty, M. M., Ameis, S., Schachar, R., Voineskos, A. N., & Wheeler, A. L. (2019). Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury. Biological Psychiatry, 85(5), 408-416. https://doi.org/10.1016/j.biopsych.2018.06.024

Stojanovski S, et al. Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury. Biol Psychiatry. 2019 03 1;85(5):408-416. PubMed PMID: 30119875.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury. AU - Stojanovski,Sonja, AU - Felsky,Daniel, AU - Viviano,Joseph D, AU - Shahab,Saba, AU - Bangali,Rutwik, AU - Burton,Christie L, AU - Devenyi,Gabriel A, AU - O'Donnell,Lauren J, AU - Szatmari,Peter, AU - Chakravarty,M Mallar, AU - Ameis,Stephanie, AU - Schachar,Russell, AU - Voineskos,Aristotle N, AU - Wheeler,Anne L, Y1 - 2018/07/12/ PY - 2018/02/12/received PY - 2018/06/12/revised PY - 2018/06/28/accepted PY - 2018/8/19/pubmed PY - 2020/2/6/medline PY - 2018/8/19/entrez KW - Attention-deficit/hyperactivity disorder KW - Diffusion tensor imaging KW - Magnetic resonance imaging KW - Polygenic score KW - Traumatic brain injury KW - Youths SP - 408 EP - 416 JF - Biological psychiatry JO - Biol Psychiatry VL - 85 IS - 5 N2 - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a major sequela of traumatic brain injury (TBI) in youths. The objective of this study was to examine whether ADHD symptoms are differentially associated with genetic risk and brain structure in youths with and without a history of TBI. METHODS: Medical history, ADHD symptoms, genetic data, and neuroimaging data were obtained from a community sample of youths. ADHD symptom severity was compared between those with and without TBI (TBI n = 418, no TBI n = 3193). The relationship of TBI history, genetic vulnerability, brain structure, and ADHD symptoms was examined by assessing 1) ADHD polygenic score (discovery sample ADHD n = 19,099, control sample n = 34,194), 2) basal ganglia volumes, and 3) fractional anisotropy in the corpus callosum and corona radiata. RESULTS: Youths with TBI reported greater ADHD symptom severity compared with those without TBI. Polygenic score was positively associated with ADHD symptoms in youths without TBI but not in youths with TBI. The negative association between the caudate volume and ADHD symptoms was not moderated by a history of TBI. However, the relationship between ADHD symptoms and structure of the genu of the corpus callosum was negative in youths with TBI and positive in youths without TBI. CONCLUSIONS: The identification of distinct ADHD etiology in youths with TBI provides neurobiological insight into the clinical heterogeneity in the disorder. Results indicate that genetic predisposition to ADHD does not increase the risk for ADHD symptoms associated with TBI. ADHD symptoms associated with TBI may be a result of a mechanical insult rather than neurodevelopmental factors. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/30119875/full_citation DB - PRIME DP - Unbound Medicine ER -

Tags

Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury.Biol Psychiatry. 2019 Mar 01; 85(5):408-416.BP