In a just published paper researchers from the University of Chicago report that a genetic predisposition toward liking the effects of amphetamines (specifically, d-amphetamine, the active ingredient of Adderall) might be associated with a decrease in the risk for schizophrenia and, incidentally, also attention deficit hyperactivity disorder (ADHD).
What did they do?
The researchers gave d-amphetamine to almost 400 people. The experiment was done in a double-blind, placebo-controlled manner, meaning that no one (neither the volunteers nor the researchers) knew what they took and all the people in the study actually took not only d-amphetamine (2 different doses) but also identically looking sugar pills (placebo). Following the ingestion of the study pills (amphetamine and placebo) the study subjects completed a number of questionnaires about how they felt after whatever it was that they have just taken. Everyone also completed a type of genetic testing where multiple single points in the DNA code known as single nucleotide polymorphisms (SNPs) are characterized. Finally, the researchers looked at the relationships between each of these SNPs and the subjects response to amphetamine.
What did they find?
Genetic variants associated with enjoying d-amphetamine were also associated with a decreased risk for schizophrenia.
Does it make sense?
To some extent.
Amphetamines are dopamine boosters. Having too much dopamine in some parts of the brain is thought as a basic problem in schizophrenia. But if you have too much dopamine to start with than you wouldn't get much a boost from a dopamine booster, would you? Thus if you are too high on dopamine to start with you will
1. NOT enjoy taking any dopamine boosters
2. Might be at risk for schizophrenia
While schizophrenia is treated with drugs that tend to block dopamine effects, ADHD is treated with drugs that increase dopamine effects. In other words, same genetic "detail" is associated with two complete opposite dopamine at-risk perturbations (high dopamine in schizophrenia, low dopamine in ADHD).
This is one BIG puzzling finding of the study.
How can this be?
1. Despite fairly solid design and cross-checks this is a relatively small study of only normal people. Hopefully future studies will confirm (replicate) these findings. Till then, tongue in check, we shall wait and see.
2. If this is a true finding our current understanding of schizophrenia= "dopamine excess" and ADHD="dopamine deficit" might be only part of the story.
Even if this is how things end does this not imply that this is how things start? Not necessarily.
May be that... to like d-amphetamine might require more robust dopaminergic checks and balances to start with... that in turn might protect against dopaminergic issues of any kind further down the road. Or, a frail dopaminergic system, would neither allow its owner to get an feeling good dopaminergic boost from amphetamines, nor protect from future dopaminergic dysregulation failures.
And the take home lesson is?
First do not use amphetamines, methamphetamines or the like to assess your risk for schizophrenia or ADHD.
Instead of getting euphoric (if you have the "right" genotype) you might end up really sick and in the psychiatric hospital (if you have the wrong genotype).
That being said this study opens new doors for assessing the genetic risk for major psychiatric issues in the future.
I like the idea of using a psychological experience (in this case the effect of taking a drug) as a lamp to guide one's journey in Ali Baba's cave of genetic treasures. When it comes to genetics this is the equivalent of travelling off the beaten path. Typically, geneticists take people who have a condition and then do all sorts of genetic tests in an attempt to understand what are the responsible genes. The problem with this approach is that your findings will be a direct reflection of how well your target condition is defined. For well defined target conditions - such as Huntington's - this model works well. But when it comes to psychiatric conditions, most of which tend to vary a good deal in between patients or in the same patient over time - this model might not be the best way to go about getting the right genes. And that is right were this new idea of looking for genes not linked to diagnosis but psychological traits might make a difference.
Hart AB1, Gamazon ER, Engelhardt BE, Sklar P, Kähler AK, Hultman CM, Sullivan PF, Neale BM, Faraone SV; Psychiatric Genomics Consortium: ADHD Subgroup, de Wit H, Cox NJ, Palmer AA: Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder.Proc Natl Acad Sci U S A. 2014 Apr 7. [Epub ahead of print]