Genetic variants associated with enjoying the effects of d-amphetamine—the active ingredient in Adderall—are also associated with a reduced risk for developing schizophrenia and attention deficit hyperactivity disorder (ADHD), report scientists from the University of Chicago in the Proceedings of the National Academy of Sciences on April 7. The results support a long-standing hypothesis that dopamine, the neurotransmitter connected with the euphoric effects of amphetamine, is related to schizophrenia and ADHD.
“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, PhD, associate professor of human genetics at the University of Chicago. “Our study provides new insights into the biology of amphetamine and how it relates to the biology of risk for these psychiatric diseases.”
Palmer and his team previously conducted a genome-wide association study (GWAS) to identify genetic variants associated with experiencing the euphoric effects of amphetamine, which is thought to affect risk for drug abuse. Almost 400 volunteers were given d-amphetamine in a double-blind, placebo-controlled experiment. They were then asked to report how the drug made them feel using carefully designed questionnaires. The researchers measured genetic differences between these subjects at approximately a million sites throughout the genome to identify variations in the DNA code known as single nucleotide polymorphisms, or SNPs. They assessed the relationships between each of these SNPs and sensitivity to amphetamine.
Using data from other large-scale GWAS studies, the team examined these same SNPs for possible overlapping associations with psychiatric disorders. Through rigorous statistical testing they found that an unexpectedly large number of SNPs were associated with both sensitivity to amphetamine and risk of developing schizophrenia or ADHD. This suggested that these traits are influenced by a common set of genetic variants.
Moreover, a significant proportion of this observed overlap appeared to be caused by variants that increased enjoyment of the effects of amphetamine but decreased the risk for both psychiatric diseases.