People with a genetic variant that results in euphoria-like feelings after taking d-amphetamine (the active ingredient in Adderall) have a reduced risk for developing attention deficit hyperactivity disorder (ADHD) and schizophrenia, according to scientists from the University of Chicago.
The findings, published in the journal Proceedings of the National Academy of Sciences, add to the long-standing evidence that dopamine — the neurotransmitter responsible for the euphoric feeling of amphetamine — is related to schizophrenia and ADHD.
Schizophrenia is usually treated with drugs that block dopamine signaling, while ADHD is treated with medications that enhance dopamine signaling (such as d-amphetamine). These findings suggest that dopamine’s role is far more complex than previously thought.
“Some of the variants that make you like amphetamine also appear to make you less likely to develop schizophrenia and ADHD,” said study leader Abraham Palmer, associate professor of human genetics. “Our study provides new insights into the biology of amphetamine and how it relates to the biology of risk for these psychiatric diseases.”
Previously, Palmer and his team had conducted a study to identify the genetic variants found in those who experience euphoric effects after taking amphetamine — a phenomenon thought to affect risk for drug abuse.
Nearly 400 participants were given d-amphetamine in a double-blind, placebo-controlled experiment and were asked to explain how the drug made them feel. The researchers then assessed the relationships between variations in the DNA code and sensitivity to amphetamine.
Through rigorous statistical testing, the researchers discovered that a significantly large number of variations were associated with both sensitivity to amphetamine and risk of developing schizophrenia or ADHD. This suggests that these traits are influenced by a common set of genetic variants.
Furthermore, a large proportion of this overlap appeared to be caused by variants that increased enjoyment of the effects of amphetamine, but lowered the risk for both mental disorders.
“While this approach would not be a useful diagnostic test, we expect that people who like the effects of amphetamine would be slightly less likely to develop schizophrenia and ADHD,” Palmer said, “and people who did not like amphetamine, we would predict, are slightly more likely to develop these diseases.”
“What is particularly striking is that by examining people’s responses for just a few hours after taking a drug, we can identify an underlying genetic propensity that can manifest as a psychiatric disease over the course of a lifetime,” he said.
The researchers plan to further investigate the variations identified in this study for their functional roles in amphetamine euphoria, schizophrenia, and ADHD. Palmer also hopes to explore genetic predispositions toward liking or disliking other therapeutic drugs, and whether sensitivity to those drugs might also overlap with the diseases for which these drugs are designed to treat.
Source: University of Chicago