Optimal Management of ADHD in Pediatric Population - Episode 2

The Neuroscience of Pediatric ADHD

November 9, 2021
Theresa R. Cerulli, MD

An expert psychiatrist explains the neuroscience of attention-deficit/hyperactivity disorder (ADHD) in the pediatric population.

Theresa R. Cerulli, MD: The neuroscience of ADHD [attention-deficit/hyperactivity disorder] is fascinating. It’s the reason I became so subspecialized in working with children, adolescents, and adults with this condition. I’m a neuropsychiatrist and always had an interest in the interface between medicine, neurology, and psychiatry, and ADHD really fits that mold. The neuroscience of ADHD, I’ll break it into 4 categories. Think about the genetics, the neuroanatomy, the neural networks, and neurotransmitters that are involved. We know that these objective measures have shown that there are differences in those 4 areas between children and adults with ADHD and children and adults without ADHD. Genetics are strong. Let’s start with that. The heritability factor is 0.77. That means that it’s mostly inherited. In other words, 77% of the time, if you’ve been diagnosed with ADHD, it’s because of the genes you’re carrying, so genetics plays a major role in this condition. We have some candidate genes as we call them. It’s not that we have 1 gene identified, but a series of what seem to be potential candidates and the combinations thereof of genetic differences that seem to then present in this heterogeneous condition we call ADHD.

There are neuroanatomical differences as well, meaning structures look different in the brain. Particularly in the prefrontal cortex, the frontal lobe, there’s smaller volume and delayed cortical development to that volume. This may be familiar from studies that have been done on peak cortical thickness in children. When we talk about children with ADHD having delayed maturation, we weren’t talking so much about their social and emotional development. That was the neuroscience; that was showing that the prefrontal cortex in children with ADHD lags in its thickness, in other words, its development, by about 2 and a half years behind the child without ADHD. Literally, there’s brain growth to come in the prefrontal cortex that’s a bit delayed, but does seem to catch up, and that’s the good news.

Neural networks are also different. We covered genetics and neuroanatomy, and now let’s talk about neural networks. What do we mean by that? How does one part of the brain talk to another part of the brain? That connectivity is affected differently for children and adults with ADHD versus not. An example, there was a study. This is an oldie but a goodie, I’ll call it, by [George] Bush, [MD, MMSc,] back in 1998, that looked at doing functional MRI scans in patients with ADHD and without, while they were doing a concentration task. It was a neuropsychology testing measure called the Stroop. It’s a test of attention that you probably have read much about when you’re reviewing your neuropsychological testing reports on your patients. The Stroop test was done, again, with the patient in the functional MRI. Half of the children and adults had ADHD and half didn’t. The areas of the brain that light up doing a concentration task were different for the non-ADHD population. The anterior cingulate cortex lights up. It’s an area of the brain that’s more efficient, typically, in involvement in attention concentration, whereas for those with ADHD, that area of the brain stayed silent. People with ADHD are using less efficient brain areas to be able to do the same focus concentration tasks. It’s maybe not as direct and not as efficient circuitry that’s being used. All the circuitry is there, but it’s lighting up a bit differently.

Fourth, neurotransmitters. We know there are neurotransmitter differences and the way the neurotransmitter levels shift, and the way medications affect neurotransmitter levels in ADHD matters. That’s how we often treat. The medications we use affect dopamine and norepinephrine. I’ll say that our understanding of neurotransmitter involvement has changed over the years as to our understanding of the condition, and it seems that the dopamine, norepinephrine story may not be the whole story. There’s some evidence of serotonin potentially playing a role in ADHD as well. There seems to be a role for serotonin in executive control and in aggression, which sometimes you’ll see with that real emotional impulsive-type of ADHD.

Transcript edited for clarity.

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