Attention deficit hyperactivity disorder (ADHD), currently the most common childhood-onset behavioral disorder, is nothing if not controversial. Nearly every aspect of ADHD from diagnosis to prevalence to medication, and even its mere existence, is disputed by at least one ‘concerned’ group. And honestly, who could blame parents for being hesitant to medicate their young children, especially since medications come with risks? However, ADHD is a very real (and prevalent) disorder which has discrete neurochemical and, as more and more research is suggesting, genetic causes. It has been linked with one neurochemical in particular.
What neural structures are theorized to underly the symptoms of ADHD? How is ADHD treated, and how does the most popular drug for it, Ritalin, work?
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Reduced Brain Activity in ADHD Patients
ADHD affects from 5-10% of children and adolescents, with boys 8 times more likely than girls to have it. The disorder is marked by an inability to focus attention and hyperactive/impulsive behavior. Often these symptoms are paired with poor social skills and difficulties at school, which makes for a very complex situation. One early study in 1990 discovered that brain activity was 8.1% lower in 30 of 60 brain region in adults who suffered from ADHD (measured by global glucose metabolism). The regions with the most significant decreases in activity were the premotor cortex and the superior prefrontal cortex (shown below, circled), which are regions which (among other things) mediate impulse control. That same year Biederman et al. reported that 28.6% of parents who are diagnosed with ADHD have a child who also has the disorder; the cautious suggestion was made that ADHD may have some genetic underpinnings. The next 17 years would lend much evidence to that effect.
So far over 10 genes have been suspected to be involved in the manifestation of ADHD, and many of these genes center around dopamine receptors or dopamine transporting molecules. Also, there seems to be no one gene which guarantees ADHD, but rather certain genes have been identified as denoting susceptibility to ADHD. (For the specific genes and there locations, go here.) Some of the genes may increase dopamine receptors in certain parts of the brain which may have the effect of depleting dopamine–which, as you will see, is an important player in ADHD.
Dopamine and Norepinephrine
ADHD was found to be the result of a deficiency of a specific neurotransmitter — here, norepinephrine. Like all neurotransmitters, norepinephrine is synthesized within the brain; however norepinephrine synthesis requires dopamine as an intermediate step. Specifically, the basic building block of each norepinephrine molecule is dopa; this molecule is converted into dopamine, which is then converted into norepinephrine. This is the normal process. Theoretically, if this dopa-to-norepinephrine synthesis is altered (say by certain genes), low levels of norepinephrine and ADHD-like symptoms could occur. Conversely, drugs which provide extra levels of norepinephrine relieve the symptoms of ADHD.
Its likely that the full spectrum of ADHD symptoms is not solely attributed to the prefrontal cortex, but rather entire pathways which interact together. These pathways do include the frontal/prefrontal areas (attention, impulse control) but also the limbic system (regulates emotions), the basal ganglia (this is the brain’s “router,” directing information), and the reticular activating system (affects attention and impulses, motivation). Since these areas communicate with each other, its likely that neurochemical problems in one area may affect others.
Drugs for ADHD
Ritalin and many other popular ADHD drugs (ie, Adderal) are stimulants: they make the brain produce more norepinephrine, relieving the symptoms of ADHD for as long as the drug is in the person’s system. About 4 million Americans are currently on Ritalin or a similar stimulant, and about 70% of those diagnosed with ADHD respond to this class of drug. Like any drug, there are costs and benefits to treatment which should be weighed with a health provider. According to the graph below, the United States and Canada have seen sharp increases in Ritalin prescriptions over the past few years.
Other ADHD drugs (like Strattera) are selective norepinephrine re-uptake inhibitors, which means it prevents norepinephrine from being degraded in the synapse. A potentially promising new ADHD drug (modafinil) was recently abandoned during clinical trails just this month when one of 933 children taking the drug developed a serious skin condition. This drug would have been an alternative to the stimulant variety, and focused more on producing states of wakefulness.
Interestingly, the mystery of ADHD doesn’t end with genes and neurotransmitters, as there is a well-documented environmental effect. For example, babies born prematurely face a significantly greater risk of developing ADHD than full-term babies (socioeconomic status was controlled for). Infants born at “34 to 36 weeks’ gestation had a 70% greater risk of developing ADHD. And babies born before 34 weeks were nearly three times as likely to develop the disorder as those born at term.” However one theory states that premature babies are a higher risk for hypoxia in the womb, which in animal models led to increased dopamine receptors in the brain. More dopamine receptors would, in turn, mean less norepinephrine in the brain as the required substrate (dopamine) would have a higher likelihood of being bound or degraded before it could be synthesized into norepinephrine.
One last mention: an interesting study conducted at Chicago Medical School suggests that children diagnosed with ADHD who do receive Ritalin have a reduced likelihood of developing a drug or alcohol problem in adulthood. It is thought that the stimulants actually reduce the pleasurable effect that the drug elicits from the brain, making drug-seeking behavior and addiction more unlikely. Another explanation is that the stimulant conveys improved impulse control which reduces the likelihood of partaking in risky behaviors like drug abuse, and increases the likelihood of performing well in school and developing positive social skills which would deter drug abuse.