The Molecular Genetics of ADHD

Molecular genetic studies have already implicated several genes as mediating the susceptibility to ADHD. Researchers have examined candidate genes in dopamine pathways because animal models, theoretical considerations, and the effectiveness of stimulant treatment implicate dopaminergic dysfunction in the pathophysiology of this disorder. Dopamine is a neural trans-

= D4 dopamine receptor j = dopamine transporter

dopamine

Dopamine is a neurotransmitter in the brain and is used in neural pathways involved in both movement control and pleasure/reward systems. Dopamine released by one neuron crosses the synapse to stimulate the adjacent neuron. It is broken down by glial cells.

mitter in the brain used in both movement control and pleasure/reward systems. In its simplest form, the dopamine hypothesis holds that excess clearance of dopamine between neurons may contribute to ADHD.

Many studies have focused on the D4 dopamine receptor gene (DRD4) which encodes a protein receptor that mediates the post-synaptic action of dopamine. A meta-analysis of these studies showed a small but statistically significant association, which could not be accounted for by any single study or by publication biases. Although the nature of the mutations in DRD4 have not been conclusively described, a version of the gene known as the 7-repeat allele has generated much interest because this allele causes a blunted response to dopamine and has been implicated in novelty seeking, a personality trait of many ADHD patients.

Several authors have reported an association between ADHD and a particular allele of the dopamine transporter (DAT) gene. This finding has been replicated by some, but not all studies. The link between the DAT gene and ADHD is further supported by a study that relates this gene to poor methylphenidate response in humans, a "knockout" mouse study showing that its elimination leads to hyperactivity in mice, and two molecular neu-roimaging studies that found elevated DAT density in the striatum of ADHD adults.

Molecular genetics studies of ADHD have also targeted other genes that are related to the dopamine system. Four studies have examined the Catechol-O-Methyltransferase (COMT) gene, whose protein product breaks down dopamine and norepinephrine. Although one study found ADHD was associated with the high-activity form of COMT, three others could not replicate the finding. Other candidate genes that show promising results for ADHD are the D5 dopamine receptor gene and the serotonin striatum part of the midbrain oooc ,oc

1B receptor. This latter finding is intriguing because, although serotonergic medicines do not help ADHD symptoms, these systems have been implicated in animal models of the disorder. see also Behavior; Disease, Genetics of; Psychiatric Disorders; Twins.

Stephen V. Faraone

Bibliography

Faraone, S. V., D. Tsuang, and M. T. Tsuang. Genetics of Mental Disorders: A Guide for Students, Clinicians, and Researchers. New York: Guilford, 1999.

Faraone, S. V., and A. Doyle. "The Nature and Heritability of Attention Deficit Hyperactivity Disorder." Child and Adolescent Psychiatric Clinics of North America 10 (2001): 299-316.

Faraone, S. V., and J. Biederman. "Neurobiology of Attention Deficit Hyperactivity Disorder." Biological Psychiatry 44 (1998): 951-958.

Attorney

Attorneys involved with genetics include criminal prosecutors (district attorneys), public defenders, environmental lawyers, family lawyers, and patent attorneys. Genetics is relevant in the areas of identification of suspects and victims, identification of illegal goods (for example, items that involve the killing of endangered animals), environmental monitoring for harmful microorganisms, parentage determinations, and the patenting of genetic materials.

While all of these different types of lawyers may need to be somewhat familiar with the fundamentals of genetics, attorneys who work on gene patents must be very familiar with both genetics and biochemistry, as well as with patent law. The majority of these patent attorneys specialize in biotechnology. Most biotechnology patent attorneys have advanced degrees, with many having Ph.D.s in genetics, microbiology, molecular biology, biochemistry, or related fields. In addition to having a strong science background, patent attorneys must be licensed to practice law in at least one state, and must pass a registration examination administered by the U.S. Patent and Trademark Office (USPTO).

Patent agents, as well as patent attorneys, can represent inventors before the USPTO. Patent agents have strong science backgrounds and must pass the USPTO registration examination, but are not licensed to practice law in any state. In addition to having very strong science backgrounds and the ability to work closely with inventors, patent attorneys and agents must enjoy reading complex scientific literature and be proficient at scientific writing. A large portion of the job involves writing scientific documents in the form of patent applications. Thus, people who enjoy reading and writing about scientific topics are well suited to the profession.

Patent attorneys and agents typically work in law firms, private companies, the U.S. Patent and Trademark Office (patent examiners), or in the technology transfer offices of universities and public institutions such as hospitals and research facilities, although some work out of their homes as solo practitioners. Patent attorneys and agents often know about ground breaking developments long before the public or others in their fields. This makes the career very interesting, exciting, and enjoyable. However, because of

ADHD Helping Your Anxious Child Audio

ADHD Helping Your Anxious Child Audio

Has Your Child Been Diagnosed With ADHD Is Coping With Your Child's Behavior Wearing You Out Are You Tired of Searching For Answers An ADHD child does not have to have a dark cloud over his or her head. If You've Got Burning Questions About ADHD, I've Got Answers.

Get My Free Audio Book


Post a comment