Brain Injury an Independent Risk Factor for ADHD in Kids

Damian McNamara

September 06, 2018

Mild traumatic brain injury (mTBI) appears to be an independent risk factor for attention-deficit/hyperactivity disorder (ADHD) that is separate and distinct from developmental ADHD caused by genetic factors, new research shows.

"Our research suggests there may be more than one type of ADHD. ADHD is classically considered a neurodevelopmental and highly heritable disorder. However, our research found that there was no relationship between genetic risk for ADHD and symptom severity in youth with a history of mild TBI," study investigator Sonja Stojanovski, a researcher at The Hospital for Sick Children, and a Doctorate of Science candidate at the University of Toronto, Ontario, Canada, told Medscape Medical News.

For clinicians diagnosing and treating pediatric ADHD, this finding adds support to screening for a history of mTBI in this population, the investigators note.

The study was published online July 12 in Biological Psychiatry.

ADHD Common Following TBI

mTBI is common in adolescents with approximately 1 in 5 reporting a previous concussion. It is associated with persistent psychiatric symptoms in a significant proportion of youth, making it "an important risk factor to be addressed by treating physicians and mental health professionals," the researchers write.

The investigators also note that attention problems and disinhibited behavior are common sequelae of TBI and that as many as 50% of children develop symptoms of ADHD soon after TBI.

While in many cases such symptoms resolve over time, between 14% and 21% of youths admitted to the hospital with TBI present with a new ADHD diagnosis. "This prevalence makes ADHD the most common disorder to develop following TBI in youths," the investigators note.

"It stands that a significant number of ADHD cases in the general population have co-occurring ADHD and mild TBI, with approximately half of these ADHD cases acquired post-TBI," Stojanovski said.

To determine whether TBI contributes to the development of ADHD in a manner that is distinct from genetic risk for ADHD, the researchers assessed 3611 participants age 8 years to 21 years old recruited through the Center for Applied Genomics at the Children's Hospital in Philadelphia, Pennsylvania.

They compared the origins of ADHD symptoms in 418 youth with a history of TBI and 3193 with no such history. Participants' medical history, ADHD symptoms, genetic data, and neuroimaging data were assessed.

The relationship of TBI history, genetic vulnerability, brain structure, and ADHD symptoms was examined by assessing ADHD polygenic score, basal ganglia volumes, and fractional anisotropy in the corpus callosum and corona radiata.

The investigators calculated a polygenic risk score based on the best genetic evidence to date. Interestingly, they only scored participants of white ancestry to avoid possible confounding due to ethnic differences between the current study sample and the ADHD genome-wide association study from which the polygenic score was derived.

They also used T1-weighted MRI to compare the caudate, putamen, accumbens, and globus pallidus volumes between participants with and without a history of mTBI.

Two Types of ADHD

In addition, they calculated fractional anisotropy from diffusion tensor imaging of white matter tracts affected by traumatic axonal injury — specifically the corpus callosum and corona radiata.

The investigators found participants with a history of mTBI had a significantly higher mean ADHD symptom severity score of 6.8, compared with 7.1 among those without a brain injury history (P = .002). However, this score did not significantly differ for the group at higher risk for persistent ADHD (P = .06).

As the researchers expected, the polygenic score was associated with increased ADHD symptom severity. However, the link was significant only in the group with no mTBI history (P = .004) and not for those positive for mTBI history (P = .70).

"This suggests that in individuals who experience TBI, the physical insult to the brain and resulting alterations in structure and function may be influential contributors to the presentation of post-TBI ADHD symptoms, whereas additive genetic predisposition contributes to developmentally acquired ADHD," the investigators write.

The researchers found a smaller caudate volume was associated with greater ADHD symptoms scores in the overall cohort (P = .007).  In contrast, the volumes of the putamen, accumbens, and globus pallidus were not associated with the number of ADHD symptoms.

They did observe a larger putamen volume when they compared the higher-risk mild TBI group to the cohort without a TBI history (P = .01).

In terms of the fractional anisotropy findings, the results showed that "decreased white matter integrity was associated with higher levels of ADHD symptom severity in youth with mild TBI, whereas among youth without history of TBI, an increase in white matter integrity was associated with greater ADHD symptom burden," Stojanovski said.

"This suggests traumatic damage to the genu of the corpus callosum may be associated with developing ADHD after a mild TBI," she added.

The investigators found no significant interactions or main effects between ADHD symptom severity and fractional anisotrophy related to the corpus callosum body, splenium, or corona radiata.

More Research Needed

The researchers note that the study has several important limitations.

The first is that the study was retrospective and therefore "we cannot distinguish pre- and postinjury ADHD and must assume that the participants with a history of TBI are reporting symptoms that manifest before and after injury."

A second potential limitation is that the polygenic score may not consider all genetic risks.

"This research suggests that what we currently know about genetic risk for ADHD may not be a useful in predicting ADHD after TBI," Stojanovski said.

"If these results are corroborated by future studies, there may be a day when predicting who will develop ADHD after TBI would be facilitated by focused in vivo neuroimaging to assess damage to the corpus callosum," she added.

Replication of the current findings in a comparable dataset and a prospective study design is warranted, the researchers note. Stojanovski also plans to expand her focus to brain networks.

"We know that damage to one region of the brain will affect all connected regions because the brain is structured as a complex network. My current project in the lab is focusing on modeling brain structure and function as networks in order to understand how TBI affects network properties related to outcome after injury."

Screening Warranted

Commenting on the findings for Medscape Medical News, Stephanie Hartselle, MD, an assistant professor of psychiatry, Brown University, Providence, Rhode Island, and a member expert for the American Academy of Child and Adolescent Psychiatry, said it's well known that mTBI and ADHD are linked with a "high suspicion that the risk is bidirectional."

"The researchers found one potential area of the brain, critical to attention, concentration, and impulse control, to be smaller in children having experienced mild TBI, corresponding to high symptoms of ADHD.

"While the findings make sense neurobiologically, the study itself had some major flaws in how children were compared, the ratings systems that were used, and their ability to draw conclusions using these comparison groups," she added.  

While the current the study may not change clinical practice, she added, the results support screening for ADHD following TBI.

"Physicians need to continue to consider the consequences of even mild TBIs as damage to the delicate structures governing attention and focus may lead to new brain dysfunction," she said. "Asking about symptoms of ADHD after mild TBI, even in a child who has not previously had these difficulties, would be prudent."

The SickKids Foundation and multiple National Institutes of Health grants funded the study. Stojanovski and Hartselle have disclosed no relevant financial relationships.

Biol Psychiatry. Published online July 12, 2018. Abstract

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