Elsevier

Biological Psychiatry

Volume 85, Issue 5, 1 March 2019, Pages 408-416
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2018.06.024Get rights and content

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.

Section snippets

Philadelphia Neurodevelopmental Cohort

Participants were subjects from the Philadelphia Neurodevelopmental Cohort, a population-based sample of children and adolescents aged 8 to 22 years (31) (see Supplemental Methods). Participants (aged 11–21 years) and parents or guardians (of those age 17 years or under) were administered a structured interview, the GOASSESS (32), which screened for psychopathology and included a comprehensive medical history. The GOASSESS is abbreviated and modified from the epidemiologic version of the

Sample Characteristics

Of participants who met inclusion criteria for the ADHD symptom analysis (n = 3611), 11.6% (n = 418) reported at least one previous mild TBI, and 38.5% (n = 161) of these participants with mild TBI reported headache, loss of consciousness, or amnesia associated with the injury, qualifying them as high risk for persistent deficits. Injury characteristics of the TBI participants within each analysis group are summarized in Supplemental Table S1A to S1D. Within the ADHD symptom analysis sample,

Discussion

Here, we examined genetic and brain structural correlates of ADHD symptoms in a community sample of youths with and without a history of mild TBI. Youths with mild TBI reported increased ADHD symptom severity, consistent with previous studies 7, 8. Assessment of the relationship between polygenic risk and ADHD symptoms revealed that, as expected, polygenic score was associated with increased ADHD symptom severity, although this relationship was driven by youths with no TBI. Caudate volume was

Acknowledgments and Disclosures

Support for the collection of the data sets was provided by Grant No. RC2MH089983 awarded to Raquel Gur and Grant No. RC2MH089924 awarded to Hakon Hakonarson. Funding was provided by the SickKids Foundation and the following National Institutes of Health grants: Grant No. R01MH099167 (to AV), Grant No. U01CA199459 (to LJO), Grant No. R03NS088301 (to LJO), Grant No. P41 EB015898 (National Center for Image-Guided Therapy), and Grant No. P41 EB015902 (Neuroimaging Analysis Center).

All participants

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