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Biol Psychiatry. 2018 Jul 12. pii: S0006-3223(18)31669-X. doi: 10.1016/j.biopsych.2018.06.024. [Epub ahead of print]

Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury.

Author information

1
Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
2
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.
3
Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
4
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
5
Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada.
6
Cerebral Imaging Centre, Douglas Institute, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
7
Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
8
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.
9
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.
10
Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
11
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.
12
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.

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.

KEYWORDS:

Attention-deficit/hyperactivity disorder; Diffusion tensor imaging; Magnetic resonance imaging; Polygenic score; Traumatic brain injury; Youths

PMID:
30119875
PMCID:
PMC6330150
[Available on 2020-01-12]
DOI:
10.1016/j.biopsych.2018.06.024

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