Polygenic risk and neural substrates of attention-deficit/hyperactivity disorder symptoms in youths with a history of mild traumatic brain injury
Open accessAbstract
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.
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Rarely, ADHD-like symptoms arise from severe early deprivation, a single gene abnormality, or early traumatic brain injury.
“In rare cases, however, ADHD-like symptoms can be caused by extreme deprivation early in life (Kennedy et al., 2016), a single genetic abnormality (Faraone and Larsson, 2018), or traumatic brain injury early in life (Stojanovski et al., 2019).”
From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Stojanovski et al., 2019
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Cites
Diagnostic and Statistical Manual of Mental Disorders, 5th ed.
Carter, M. J. (2014) · Therapeutic Recreation Journal · Cited by 15,154 · see citing works
3D Slicer as an image computing platform for the Quantitative Imaging Network
Fedorov, A., Beichel, R., Kalpathy–Cramer, J., Finet, J., Fillion‐Robin, J., Pujol, S., Bauer, C., Jennings, D. L., Fennessy, F., Milan Sonka, A., et al. (2012) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2012.05.001 · Cited by 9,095 · see citing works
The worldwide prevalence of ADHD: a systematic review and metaregression analysis
Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., & Rohde, L. A. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.6.942 · Cited by 5,346 · see citing works
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821 · see citing works
Molecular genetics of attention-deficit/hyperactivity disorder
Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., & Sklar, P. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.11.024 · Cited by 2,357 · see citing works
ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Demontis, D., Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Walters, R. K., Martin, J., Mattheisen, M., Als, T. D., Agerbo, E., Baldursson, G., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0269-7 · Cited by 2,203 · see citing works
Self-citationThe Prevalence of DSM-IV Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review
Willcutt, E. G. (2012) · Neurotherapeutics · doi:10.1007/s13311-012-0135-8 · Cited by 2,160 · see citing works
Cassidy, J. D., Carroll, L., Peloso, P. M. J., Borg, J., von Holst, H., Holm, L. W., Kraus, J. F., & Coronado, V. G. (2004) · Journal of Rehabilitation Medicine · doi:10.1080/16501960410023732 · Cited by 1,612 · see citing works
Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review
Assaf, Y., & Pasternak, O. (2008) · Journal of Molecular Neuroscience · doi:10.1007/s12031-007-0029-0 · Cited by 1,537 · see citing works
Attention-Deficit/Hyperactivity Disorder: A Selective Overview
Biederman, J. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.10.020 · Cited by 1,343 · see citing works
Diffuse axonal injury in head injury: definition, diagnosis and grading
Adams, J. H., Doyle, D., Ford, I., Gennarelli, T. A., Graham, D. I., & Mclellan, D. R. (1989) · Histopathology · doi:10.1111/j.1365-2559.1989.tb03040.x · Cited by 1,176 · see citing works
Hoogman, M., Bralten, J., Hibar, D. P., Mennes, M., Zwiers, M. P., Schweren, L. S. J., van Hulzen, K. J. E., Medland, S. E., Shumskaya, E., Jahanshad, N., et al. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(17)30049-4 · Cited by 879 · see citing works
Nakao, T., Radua, J., Rubia, K., & Mataix-Cols, D. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11020281 · Cited by 588 · see citing works
Erskine, H. E., Norman, R. E., Ferrari, A. J., Chan, G. C. K., Copeland, W. E., Whiteford, H. A., & Scott, J. G. (2016) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2016.06.016 · Cited by 555 · see citing works
Neuroimaging after mild traumatic brain injury: review and meta-analysis
Eierud, C., Craddock, R. C., Fletcher, S., Aulakh, M., King-Casas, B., Kuehl, D., & LaConte, S. M. (2014) · NeuroImage: Clinical · doi:10.1016/j.nicl.2013.12.009 · Cited by 524 · see citing works
Neuroimaging of the Philadelphia Neurodevelopmental Cohort
Satterthwaite, T. D., Elliott, M. A., Ruparel, K., Loughead, J., Prabhakaran, K., Calkins, M. E., Hopson, R., Jackson, C., Keefe, J., Riley, M., et al. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.07.064 · Cited by 504 · see citing works
Gentry, L., Godersky, J. C., & Thompson, B. (1988) · American Journal of Roentgenology · doi:10.2214/ajr.150.3.663 · Cited by 489 · see citing works
Genome-wide association studies in ADHD
Franke, B., Neale, B., & Faraone, S. (2009) · Human Genetics · doi:10.1007/s00439-009-0663-4 · Cited by 462 · see citing works
van Ewijk, H., Heslenfeld, D. J., Zwiers, M. P., Buitelaar, J. K., & Oosterlaan, J. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.01.003 · Cited by 377 · see citing works
Performing label-fusion-based segmentation using multiple automatically generated templates
Chakravarty, M. M., Steadman, P. E., van Eede, M. C., Calcott, R. D., Gu, V. Y., Shaw, P., Raznahan, A., Collins, D. L., & Lerch, J. P. (2012) · Human Brain Mapping · doi:10.1002/hbm.22092 · Cited by 339 · see citing works
Self-citationSatterthwaite, T. D., Connolly, J. J., Ruparel, K., Calkins, M. E., Jackson, C., Elliott, M. A., Roalf, D. R., Hopson, R., Prabhakaran, K., Behr, M., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2015.03.056 · Cited by 335 · cited 2× · see citing works
“012), but negative association with ADHD symptom score in youth with TBI (t(31)=−3.”
BackgroundMethodThe National Comorbidity Survey Adolescent Supplement (NCS-A): I. Background and Measures
Merikangas, K., Avenevoli, S., Costello, E., Koretz, D., & Kessler, R. (2009) · Journal of the American Academy of Child and Adolescent Psychiatry · doi:10.1097/chi.0b013e31819996f1 · Cited by 308 · see citing works
The creation of a brain atlas for image guided neurosurgery using serial histological data
Chakravarty, M. M., Bertrand, G., Hodge, C. P., Sadikot, A. F., & Collins, D. L. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.09.041 · Cited by 295 · see citing works
Self-citationStructural brain change in Attention Deficit Hyperactivity Disorder identified by meta-analysis
Ellison-Wright, I., Ellison-Wright, Z., & Bullmore, E. (2008) · BMC Psychiatry · doi:10.1186/1471-244x-8-51 · Cited by 269 · see citing works
DTIPrep: quality control of diffusion-weighted images
Oğuz, İ., Farzinfar, M., Matsui, J., Budin, F., Liu, Z., Gerig, G., Johnson, H. J., & Styner, M. A. (2014) · Frontiers in Neuroinformatics · doi:10.3389/fninf.2014.00004 · Cited by 261 · see citing works
Imaging for the diagnosis and management of traumatic brain injury
Kim, J. J., & Gean, A. D. (2011) · Neurotherapeutics · doi:10.1007/s13311-010-0003-3 · Cited by 249 · see citing works
The Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping collaborative
Calkins, M. E., Merikangas, K. R., Moore, T. M., Burstein, M., Behr, M. A., Satterthwaite, T. D., Ruparel, K., Wolf, D. H., Roalf, D. R., Mentch, F. D., et al. (2015) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12416 · Cited by 245 · see citing works
The molecular genetic architecture of attention deficit hyperactivity disorder
Hawi, Z., Cummins, T. D. R., Tong, J., Johnson, B., Lau, R., Samarrai, W., & Bellgrove, M. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.183 · Cited by 216 · see citing works
Max, J. E., Lansing, A. E., Koele, S. L., CASTILLO, C. S., Bokura, H., Schachar, R. J., Collings, N. M., & Williams, K. E. (2004) · Developmental Neuropsychology · doi:10.1080/87565641.2004.9651926 · Cited by 214 · see citing works
Self-citationLifetime and Novel Psychiatric Disorders After Pediatric Traumatic Brain Injury
Bloom, D., Levin, H. S., Ewing‐Cobbs, L., Saunders, A. E., Song, J., Fletcher, J. M., & Kowatch, R. A. (2001) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200105000-00017 · Cited by 194 · see citing works
Mild traumatic brain injury and postconcussive symptoms in children and adolescents
YEATES, K. O. (2010) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617710000986 · Cited by 180 · see citing works
Peerless, S. J., & Rewcastle, N. B. (1967) · PubMed · Cited by 162 · see citing works
Ameis, S. H., Lerch, J. P., Taylor, M. J., Lee, W., Viviano, J. D., Pipitone, J., Nazeri, A., Croarkin, P. E., Voineskos, A. N., Lai, M.-C., et al. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.15111435 · Cited by 155 · see citing works
Self-citationPrevalence of Concussion Among US Adolescents and Correlated Factors
Veliz, P. T., McCabe, S. E., Eckner, J. T., et al. (2017) · JAMA · doi:10.1001/jama.2017.9087 · Cited by 152 · see citing works
Neurobiology of Attention Deficit/Hyperactivity Disorder
Purper‐Ouakil, D., Ramoz, N., Lepagnol-Bestel, A.-M., Gorwood, P. A. P. M., & Simonneau, M. (2011) · Pediatric Research · doi:10.1203/pdr.0b013e318212b40f · Cited by 146 · see citing works
Chen, L., Hu, X., Ouyang, L., He, N., Liao, Y., Liu, Q., Zhou, M., Wu, M., Huang, X., & Gong, Q. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.07.022 · Cited by 132 · see citing works
Armstrong, R. C., Mierzwa, A. J., Sullivan, G. M., & Sánchez, M. Á. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.04.029 · Cited by 127 · see citing works
Shaw, P., De Rossi, P., Watson, B., Wharton, A., Greenstein, D., Raznahan, A., Sharp, W., Lerch, J. P., & Chakravarty, M. M. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2014.05.003 · Cited by 126 · see citing works
Self-citationSymptoms of Attention-Deficit/Hyperactivity Disorder Following Traumatic Brain Injury in Children
Levin, H., Hanten, G., Max, J., Li, X., Swank, P., Ewing-Cobbs, L., Dennis, M., Menefee, D. S., & Schachar, R. (2007) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/01.dbp.0000267559.26576.cd · Cited by 123 · see citing works
Self-citationMax, J. E., Schachar, R. J., Levin, H. S., Ewing‐Cobbs, L., Chapman, S. B., Dennis, M., Saunders, A. E., & Landis, J. (2005) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000173292.05817.f8 · Cited by 122 · see citing works
Self-citationSlicerDMRI: Open Source Diffusion MRI Software for Brain Cancer Research
Norton, I. H., Essayed, W. I., Zhang, F., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0332 · Cited by 122 · see citing works
Max, J. E., Lansing, A. E., Koele, S. L., et al. (2004) · Developmental Neuropsychology · doi:10.1207/s15326942dn2501&2_9 · Cited by 112 · see citing works
Prevalence and Correlates of Traumatic Brain Injuries Among Adolescents
Ilie, G., Boak, A., Adlaf, E. M., et al. (2013) · JAMA · doi:10.1001/jama.2013.6750 · Cited by 104 · see citing works
Tu, T., Williams, R. A., Lescher, J. D., Jikaria, N. R., Turtzo, L. C., & Frank, J. A. (2016) · Annals of Neurology · doi:10.1002/ana.24641 · Cited by 96 · see citing works
Onnink, A. M. H., Zwiers, M. P., Hoogman, M., Mostert, J. C., Dammers, J., Kan, C. C., Vasquez, A. A., Schene, A. H., Buitelaar, J., & Franke, B. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.04.008 · Cited by 93 · see citing works
van Ewijk, H., Heslenfeld, D. J., Zwiers, M. P., Faraone, S. V., Luman, M., Hartman, C. A., Hoekstra, P. J., Franke, B., Buitelaar, J. K., & Oosterlaan, J. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2014.05.001 · Cited by 79 · see citing works
Beyond <i>DSM</i> : Seeking a Brain-Based Classification of Mental Illness
Miller, G. (2010) · Science · doi:10.1126/science.327.5972.1437 · Cited by 77 · see citing works
Wu, Z.-M., Bralten, J., Cao, Q., Hoogman, M., Zwiers, M. P., Li, A., Sun, L., Yang, L., Zang, Y., Franke, B., et al. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.223 · Cited by 77 · see citing works
Neuropsychiatry of Pediatric Traumatic Brain Injury
Max, J. E. (2014) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2013.11.003 · Cited by 62 · see citing works
Jin, C., & Schachar, R. J. (2004) · CNS Spectrums · doi:10.1017/s1092852900009019 · Cited by 55 · see citing works
Self-citationSlomine, B. S., Salorio, C. F., Grados, M. A., Vasa, R. A., Christensen, J. R., & GERRING, A. J. P. (2005) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617705050769 · Cited by 51 · see citing works
Pediatric Traumatic Brain Injury and Attention Deficit
Königs, M., Heij, H. A., van der Sluijs, J. A., Vermeulen, R. J., Goslings, J. C., Luitse, J. S. K., Poll‐The, B. T., Beelen, A., van der Wees, M., Kemps, R. J. J. K., et al. (2015) · PEDIATRICS · doi:10.1542/peds.2015-0437 · Cited by 50 · see citing works
Dimensions of Attention Associated With the Microstructure of Corona Radiata White Matter
Stave, E. A., Bellis, M. D. D., Hooper, S. R., Woolley, D. P., Chang, S. K., & Chen, S. D. (2017) · Journal of Child Neurology · doi:10.1177/0883073816685652 · Cited by 47 · see citing works
Interventions for Attention Problems After Pediatric Traumatic Brain Injury: What Is the Evidence?
Backeljauw, B., & Kurowski, B. G. (2014) · PM&R · doi:10.1016/j.pmrj.2014.04.004 · Cited by 44 · see citing works
Sinopoli, K. J., Schachar, R. J., & Dennis, M. (2011) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2011.562864 · Cited by 43 · see citing works
Self-citationMapping the Connectome Following Traumatic Brain Injury
Hannawi, Y., & Stevens, R. D. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-016-0642-9 · Cited by 40 · see citing works
Ripley, D. L., Morey, C. E., Gerber, D., Harrison-Felix, C. L., Brenner, L. A., Pretz, C. R., Cusick, C., & Wesnes, K. A. (2014) · Brain Injury · doi:10.3109/02699052.2014.919530 · Cited by 30 · see citing works
Polimanti, R. A., Chen, C., Ursano, R. J., Heeringa, S. G., Jain, S., Kessler, R. C., Nock, M. K., Smoller, J. W., Sun, X., Gelernter, J. E., et al. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2016.4550 · Cited by 25 · see citing works
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“In rare cases, however, ADHD-like symptoms can be caused by extreme deprivation early in life (Kennedy et al., 2016), a single genetic abnormality (Faraone and Larsson, 2018), or traumatic brain injury early in life (Stojanovski et al., 2019).”
Mooney, M. A., Bhatt, P., Hermosillo, R. J. M., Ryabinin, P., Nikolas, M., Faraone, S. V., Fair, D. A., Wilmot, B., & Nigg, J. T. (2021) · Psychological Medicine · doi:10.1017/s0033291719004148 · Cited by 33 · see citing works
Jendreizik, L. T., Hautmann, C., von Wirth, E., Dose, C., Thöne, A.-K., Treier, A.-K., Banaschewski, T., Becker, K., Brandeis, D., Geissler, J., et al. (2022) · Child and Adolescent Psychiatry and Mental Health · doi:10.1186/s13034-022-00529-z · Cited by 12 · see citing works
- Authors
- 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.
- Affiliations
- University of Toronto (CA)
- Broad Institute (US)
- Centre for Addiction and Mental Health (CA)
- Hospital for Sick Children (CA)
- Douglas Mental Health University Institute (CA)
- Brigham and Women's Hospital (US)
- Corresponding author
- Wheeler, Anne L.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 85
- Issue
- 5
- Pages
- 408-416
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC6330150
- OpenAlex
- W2883724802
- Cited by
- 35
- References
- 59
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 9 · 2021: 8 · 2020: 6 · 2019: 1
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (RC2MH089983, R01MH099167, RC2MH089924)
- National Cancer Institute (U01CA199459)
- National Institute of Neurological Disorders and Stroke (R03NS088301)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015902, P41EB015898)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, mild traumatic brain injury, polygenic risk, adolescents, caudate volume, basal ganglia, corpus callosum, fractional anisotropy, corona radiata, brain structure, genetic susceptibility, ADHD etiology
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Basal Ganglia, Brain Concussion, Child, Corpus Callosum, Female, Humans, Male, Severity of Illness Index, Case-Control Studies, Anisotropy, Multifactorial Inheritance, Young Adult, Diffusion Tensor Imaging, Neuroimaging, White Matter
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