Sep 10 2009

ADHD and Brain Chemistry

ADHD (attention deficit and hyperactivity disorder) is somewhat of a beleaguered and misunderstood disorder. The key controversy (and it is mainly a public, not a scientific, controversy) is whether ADHD is an actual brain disorder, a product of environmental factors (bad parenting, too much TV), or a cultural fiction. As is often sadly the case, I find the public debate largely disconnected from the scientific research.

I have no particular bias toward any kind of explanation – whether ADHD is a hardware or software problem, or an observational artifact. I believe all three kinds of entities exist. My only interest is to understand what the science says about ADHD. My reading of the literature is that the evidence strongly supports the conclusion that ADHD is a brain disorder. Of course it is modified by the environment – but at its core, it’s a problem of brain function.

A new study supports this conclusion, but before I get to that let me go over some background. The clinical definition of ADHD, like all behavioral diagnoses, is based upon having a minimum number of a list of characteristic symptoms. This kind of “squishy” diagnosis often fuels the fire of ADHD denial – but in reality many medical diagnoses are made this way. Migraine, which is not a controversial disorder, is diagnosed the same way.

The diagnostic criteria for inattention includes things like the inability to sustain attention to a task and an unwillingness to engage in a task that requires sustained mental effort. The criteria for hyperactivity include things like being very fidgity, blurting out answers before questions are finished, and difficulty awaiting one’s turn. But in addition, these symptoms must cause demonstrable impairment in school or social function.

The challenge in making a diagnosis is that all kids exhibit some of these symptoms to some degree – so some judgment and experience is required in determining if a feature is present to an excessive degree for that child’s age. This subjective aspect to the diagnosis does make it reasonable to ask the question – how do we know this is a real disorder and not just normal variation. Here we get into the difficulty of definition.

To clarify, no one says that ADHD is a disease, or that there is some pathological process going on. It may be just one end of the Bell curve of typical human variation. But the definition of a disorder only requires that there are identifiable features that deviate significantly from the mean and which cause demonstrable problems. In fact, for practical purposes it is not necessary to obsess about whether an individual meets criteria for the diagnosis (are they fidgity enough) but rather to focus on whether they are having identifiable problems, and then address those problems. The concept of ADHD is useful in understanding why certain kids may be having problems and how to address them.

That’s my practical clinician’s approach to many situation. However, in reality, school systems and other institutions need labels and allocate resources accordingly. So even though labels are imperfect and are not strictly necessary to address a problem, the system often demands them.

So what kind of disorder is ADHD? The current concept is that it is a disorder primarily of executive function. The neocortex in the frontal lobes – that part of our brains that most recently evolved, is involved with master decision-making. The frontal lobes are at the top of the hierarchy – it is here that we override our desire to eat cheesecake, we consider the long term consequences of our actions, inhibit our impulses, and focus our attention. And, like all biological functions, there is extensive variation in the degree of executive function in the population. Those with ADHD are at the low end of the Bell curve of executive function.

The last 20 years of research has strongly supported this position. Brain activity levels in suspected brain areas are consistently lower in people with clinical symptoms of ADHD. Stimulants that increase brain activity relieve symptoms and improve outcomes. There is evidence for a genetic predisposition and about 10 genes have been linked to ADHD. Low dopamine in particular has been linked to ADHD.

This brings us to the new study – published in this week’s JAMA, a study by Nora Volkow et al. shows that untreated adults (to rule out the effects of medication) had lower dopamine transporter and receptor activity in key brain regions when compared to typical controls. The results seem fairly robust and confirm what we would predict from our current model of ADHD. So yes, Tom Cruise, ADHD is a problem with brain chemistry.

Dopamine is involved (among other things) with the reward system in the brain. Animals with central nervous systems have a very basic reward system in the brain that makes us feel good when we do something that evolution wants us to do (because it enhances our survival and the spread of our genes). Eating calorie-rich food and having sex feel good and give us a dose of dopamine to our reward centers.

Those with ADHD have been observed to have some behaviors, like overeating and drug addiction, that could be explained on the basis of decreased reward response. Therefore, they need to do more to get the same reward as the average person, so they engage more in reward-seeking behavior. This study, showing lower dopamine activity in the reward centers (like the nucleus acumbens) strongly supports that conclusion.

This study adds to our understanding of ADHD and our confidence in the neuroscience models of what ADHD is. But most importantly, the more we understand the disorder the better we will be able to identify and treat it. Perhaps this may lead to treatments that target dopamine more specifically, for example.

ADHD is a highly emotionally charged diagnosis. The controversy stems partly from the fact that there is much confusion about how such diagnoses are made, the role of treatment trials, and the correlation between clinical criteria and objective measures of brain function. For cost and practical reasons we rely more on clinical criteria and treatment trials than PET scans and function MRIs to make the diagnosis – and the same is true of many entities in medicine.

But often ADHD is dismissed as an excuse for lazy parenting or schooling, as a quick fix to a complex problem, or the “medicalizing” of normal behavior. In my opinion such dismissive attitudes are not well-informed and largely stem from misconceptions about how diagnoses are made in medicine. I also think that emotions run particularly high when kids are involved, and I understand this.

But as is often the case, a thorough and sober assessment of the science is our best guide.

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