My fundamental points from yesterday evening’s talk:
* The ways we can look at learning interferences are tangled together in multiple ways.
* Common sense may be our best tool to untangle them.

One of the pleasures of preparing to speak to a group is that it encourages the speaker to do some catching up. I came across a concept – new to me, although it has apparently been around for a couple decades! – that seems to be a tool to think better about ADHD: Endophenotype. Since I could barely mention the idea in the time I had, I thought it would be fun to post about it here, so I can try to find words to describe it. I should start by saying this is all new to me this last weekend. I have no background in genetics, so this is a layman’s attempt to understand.

You know that “ADHD” is a complex entity. The diagnostic manual, DSM-IV, gives us three subtypes: predominantly inattentive, predominantly hyperactive / impulsive, and combined. Recently, we’ve seen convincing evidence that Inattentive Type ADHD probably reflects “different wiring” – has different genetic origins than the classical Combined Type. But that’s only the start: Anyone who is ADHD, or is working to help an ADHD person grow and develop, knows that no two people show their ADHD in exactly the same way. That’s leads to the notion of a phenotype: the individual expression of a particular genetic inheritance, modified by a particular environment – by a particular personal history.

There’s a lot of evidence that what we clump together under the ADHD diagnosis doesn’t come from a single genetic wiring. The individual genetic complex that we’re born with is our genotype – a blend of the genetic potentials of our parents. If we could get back to the genetic underpinnings of different ADHD individuals, if we could sort out the different wirings we call ADHD, get back to the different genotypes we clump together as ADHD, it could have huge benefits. It might mean that we could detect ADHD very early. It might mean that we could eliminate the current “guessing game” of finding the effective medication for an individual. (Put that the other way around: We have to try this medication and that because different ADHD people, with different “wirings,” will respond to different medications, and right now, we don’t have a way to differentiate those different wirings.)

But that clumping together of different wirings makes it difficult to get to the genetic underpinning, in at least two ways. First, when researchers study a group of “ADHD” children, the sample probably includes many different genotypes. Second, the terms we used to diagnose people don’t relate clearly to the fundamental wirings: What could be the genetics that underlie “Fails to give close attention to details or makes careless mistakes"?

That brings us to Endophenotype. The idea is simpler than the word: Can we find things which we know are part of what we call ADHD, which we know how to measure, and which are closer to the genetics that structured the basic wiring than are the words of our diagnostic definition? If we can identify those, then we can identify the genes involved in them. For example, we know that working memory is an important part of ADHD. We know how to measure working memory. And there’s evidence that working memory ability is heritable, that it has a genetic basis.

Here’s how Irving Gottesman explains the idea

An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward—and successful—genetic analysis. However, to be most useful, endophenotypes for psychiatric disorders must meet certain criteria, including association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in relatives, and disease association parameters. In addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis….

Now, you and I don’t care about the genetics themselves. We care about helping individuals. And no one has begun to understand what all the endophenotypes are. But maybe we can think better about what ADHD means to us or our loved ones if we can get to some of these measurable candidates. For me, I may be able to design more focused evaluation. For parents and teachers, we may be able to focus our interventions better.

Gottesman suggests three criteria for candidate endophenotypes. Here are my top-of-the-head candidate endophenotypes for ADHD. I think all of these meet at least two criteria: they can be measured, and they have a degree of heritability. The third criterion, I don’t have the background to judge, so I’m purely guessing that they may be able to be associated “with a candidate gene or gene region.” I’m going to start looking for good ways to measure these concepts, so we can think about ways to either work on the skills involved, or on accommodations to work around deficit areas.

Working Memory

Processing Speed

Perception of time

Any help thinking about candidates is much appreciated.