Pharmacogenetics

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Pharmacogenetic studies provide insights about the causal role of neurotransmitter and hormone receptors involved in a cognitive function. This approach is so powerful because it combines the strengths of psychopharmacology with those of genetics. In one of our studies on human risk taking we administered the participants either a single-dose of the dopamine precursor L-DOPA or a placebo and had everyone provide DNA samples. By analyzing specific genes, we inferred the function of their dopamine D4 receptors (DRD4). This receptor is known to be one of the targets of dopamine, but is also associated with gambling addiction. We found that those who carry a specific version of the gene, the so-called 7R variant of the DRD4 polymorphism, responded most pronouncedly to L-DOPA by showing a very prominent increase in risk taking during an experimental economics paradigm. This allows concluding that the DRD4 plays a causal role in human risk taking. This conclusion could not be drawn when using psychopharmacology or genetics alone, because on the one hand L-DOPA administration also leads to effects at other dopamine receptors, and mere genotype behavior associations remain correlative on the other hand.