A new study comparing genetics and the neural wiring of the brain suggests a diagnosis of attention-deficit/hyperactivity disorder (ADHD) results from a combination of factors. Investigators discovered that it takes many common genetic variations combining together in one individual to increase risk substantially.

At the same time, neuroimaging (MRI) experts have found differences in how the brains of people diagnosed with ADHD are functionally connected. However, it’s unclear how genetic risk might be directly related to altered brain circuitry in individuals diagnosed with ADHD.

In the new study, researchers focused their imaging analyses on selected brain regions, looking specifically at the communication between those regions and the rest of the brain in children with the diagnosis.

They discovered that one brain region’s connectivity was linked to a higher risk of ADHD. However, a second, different part of the brain seemed to compensate for genetic effects and reduce the chances of an ADHD diagnosis.

The authors believe this research will lead to a better understanding of how genetic risk factors alter different parts of the brain to change behaviors and why some people at higher genetic risk do not exhibit ADHD symptoms.

The study appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

“We are now in a phase with enough data to answer some questions about the underlying genetics of a disorder that in the past have been difficult to elucidate,” said senior author Damien Fair, Ph.D.

“Previous imaging studies had shown different functional connectivity, and we assume those have a genetic basis.”

ADHD is a neurodevelopmental psychiatric disorder that affects about 5 percent of children and adolescents and 2.5 percent of adults worldwide. The disorder is characterized by inattentive or hyperactive symptoms with many variations.

The paper focuses on 315 children between the ages of 8 and 12 who participated in a longitudinal ADHD study that began in 2008 at the Oregon Health & Science University in Portland. Fair, a neuroscientist and imaging researcher, and co-author Joel Nigg, Ph.D., a pediatric psychologist participated in the study. Robert Hermosillo, Ph.D., a postdoctoral researcher in Fair’s lab, led the study.

The research team selected three areas of the brain based on a brain tissue database that showed where ADHD risk genes were likely to alter brain activity. To measure the brain communication to-and-from these regions on each side of the brain, the researchers used resting-state non-invasive magnetic resonance imaging (MRI) scans.

To begin to bridge genetic and neuroimaging studies of ADHD, researchers used MRI to scan the brains of children. Two regions previously associated with ADHD stood out. In one, a higher ADHD genetic risk correlated with a more active brain circuit anchored by the nucleus accumbens (orange arrow). Interestingly a weaker connection anchored by the caudate nucleus (blue arrow) seemed to protect children at high genetic risk from ADHD behaviors.

Next, they calculated a cumulative ADHD genetic risk score in the children, based on recent genome-wide studies, including a dozen higher-risk genetic regions reported two years ago by a large international collaboration called the Psychiatric Genetics Consortium.

In one brain region anchored by the nucleus accumbens, they found a direct correlation with genetics. “Increased genetic risk means stronger communication between the visual areas and the reward centers,” explained Hermosillo.

Another brain region anchored by the caudate yielded more puzzling results until the researchers tested its role as a mediator between genetics and behavior.

“The less these two regions talk to each other, the higher the genetic risk for ADHD,” said Hermosillo. “It seems to provide a certain resiliency against the genetic effects of ADHD. Even among those with high risk for ADHD, if these two brain regions are communicating very little, a child is unlikely to end up with that diagnosis.”

A third region, the amygdala, showed no correlation between connectivity to the other brain regions and the genetics.

According to the authors, the findings suggest that a genetic score alone will not be enough to predict ADHD risk in individuals because the results show both a genetic and neural contribution toward an ADHD diagnosis.

A future diagnostic tool will likely need to combine genetics and brain functional measures. “The brain is not at the mercy of genes,” added Hermosillo. “It’s a dynamic system not preprogrammed for disorders. It has the capacity to change.”

Source: Elsevier

Study Probes Interaction of Genetics and Neural Wiring in ADHD