Andrew Kittleson, Winner of the 2019 Three-Minute Talks Competition
Drew Kittleson: Hi, my name is Drew Kittleson. A person's genetic makeup in concert with their environment, affects brain development, impacts behavior, and determines risk for neuropsychiatric illness. However, our understanding of the neurobiological underpinnings of this genetic influence are still poor.
Attention-Deficit/Hyperactivity Disorder or ADHD is ideal to study the genetic basis of mental illness. ADHD is the most common neurodevelopmental disorder affecting 3 to 5 percent of the population. Recent work has shown that it is highly heritable as well with estimates upwards of 80 percent.
However, there is not one ADHD gene which results in a clinical diagnosis when mutated. Rather, it is the accumulation of genes across the genome that, when combined, yield ADHD-like pathophysiology.
Previous neuroimaging studies have identified multiple structural brain changes associated with an ADHD diagnosis. But it is yet unclear which of these changes, if any, have genetic influences. Here we sought to ask how genetic influence for ADHD might affect brain structure even in healthy adults.
We collected genetic data and structural MRI scans for 482 unrelated, healthy participants across two cohorts; 265 from the Human Connectome Project, or HCP, and an additional 217 individuals from our study conducted here at the NIMH. It is important to note once again that all of these individuals were healthy and did not carry an ADHD diagnosis at time of data collection.
We hypothesize that those individuals carrying increased risk for ADHD, but without a clinical diagnosis, would demonstrate brain structural changes typically seen in clinical populations. To do this, we first acquired each person's genetic risk for acquiring ADHD, deemed a polygenic risk score, which is the sum of that person's number of risk alleles across the genome, each weighted by their own association with ADHD diagnosis.
We then looked across the entire brain for each of these participants to determine regions where individual variations in ADHD genetic risk was significantly correlated with changes in gray matter volume. We found participants across both cohorts with increased genetic risk for ADHD to demonstrate increased gray matter volume in a region of the right superior parietal lobule.
As you can see, this region is nearly identical across both cohorts, which is promising because previous neuroimaging studies in clinical ADHD populations have identified parietal regions as having delayed cortical maturation and higher gray matter volume corroborating our results.
Further, this region is known to be involved in working memory and executive functioning, both of which tend to be aberrant in clinical ADHD populations. Together these results shed light on a region which may be neurogenetically implicated in the pathophysiology of ADHD.
Additionally, in the Human Connectome Project cohort, we found those participants with increased genetic risk for acquiring ADHD to demonstrate increased gray matter volume in a region of the left, dorsolateral prefrontal cortex. This region is known to be involved in things such as executive functioning and sensory motor coordination, both of which tend to be aberrant in clinical ADHD populations as well.
Taken together these data demonstrate that those individuals harboring increased genetic risk for ADHD, but without a clinical diagnosis, tend to have brain structural changes typically seen in those with the disorder. These data shed light on neurogenetic bases of ADHD including identification of key brain targets for future investigations, and could predispose some of the behavioral phenotypes typically seen in the disorder.