You may be aware that many functions in our body, including production of hormones and other body and brain chemicals, are controlled by specific genes—the molecules of DNA that tell our cells how to develop and behave. You may not, however, have a clear idea of how this really works, and the fact is that scientists did not either until fairly recently. Mapping the human genome has helped determine some of the genes controlling specific functions, but many genes affect body systems in ways that scientists have yet to figure out. In some cases, multiple genes may be involved in complex interactions to cause an organ or a system to function properly (or improperly, as in the case of ADHD and many other disorders).
Genetic studies of ADHD have focused largely on genes involved in controlling the neurotransmitter dopamine. This is logical because medications that increase dopamine are effective treatments for ADHD. Furthermore, brain-imaging studies have identified abnormalities in the dopamine-rich frontal and striatal regions in individuals with ADHD. In animal models used to investigate ADHD, “knock-out” mice—mice missing a gene important for increasing dopamine—are hyperactive and do not respond to stimulant treatment. Their dopamine can not be increased, and they remain hyperactive.
Currently the genes most likely to cause ADHD are thought to involve dopamine regulation. The dopamine transporter (DAT) gene is the prime candidate. This gene regulates the amount of dopamine in the synapse by determining how much dopamine is reabsorbed into the presynaptic neurons. In controls, the dopamine transporter keeps the level of dopamine in the synapse relatively high. In ADHD, the DAT “overfunctions” and lowers the level of synaptic dopamine. Stimulants inhibit DAT. As a result, more dopamine remains in the synapse. Other possible causal genes control postsynaptic dopamine receptors. They affect the sensitivity of the receptors to dopamine. It may take more dopamine to activate the postsynaptic receptors in children with ADHD.
So what does this knowledge mean for treating children with ADHD? First, it may help scientists design better medications for treating ADHD. They can target the cause of the neurotransmitter problem. Second, scientists can work toward treatments, called gene therapy, that correct the genetic abnormalities by replacing the abnormal gene. Gene treatment is currently being tried for a number of serious progressive neurological disorders.
