Brain Scanning Gives Clues to How Genes Shape Behavior, Disease Risk

February 27, 2009 • Science Update

In an experiment in which people viewed changing images of slot machines, inherited differences in brain chemistry predicted the magnitude of responses in the brain to the prospect and receipt of reward. The work suggests how the subtle effect of variations in individual genes can shape behavior and contribute to risk of some mental health disorders.

One of the goals of neuroscience research is to clarify how genes that are active in the brain shape behavior, personality, and disease risk. Among the targets of this research are the genes related to neurotransmitters, which convey chemical messages between brain cells or neurons. Dopamine is a neurotransmitter that is known to have a central role in emotion and the sensation of reward. It is an important player in the brain's reward system-the "wiring" behind motivational drives.

This study focused on the genes for COMT, an enzyme that inactivates dopamine, and for DAT1, a protein that recaptures dopamine that has been released by neurons in the process of signaling between cells. Past research has established that variations (polymorphisms) in the genes for COMT and DAT1 raise or lower baseline dopamine level in the connections, or synapses, between neurons. Particular variants of these genes are associated with behavioral tendencies—an interest in novelty and risk-taking, for example—and risk of such mental health disorders as substance abuse, depression, obsessive-compulsive disorder, and schizophrenia.

Scientists in this study recruited people who had different assortments of COMT and DAT1 gene variants and therefore different levels of dopamine activity. The participants were asked to respond to a series of images on a computer screen resembling slot machines and representing different levels of reward and risk. The magnitude of brain responses—revealed by functional imaging—to situations in which participants were anticipating rewards or had received them in the "game" followed a pattern predicted by which variants of the COMT and DAT1 genes each individual carried. Brain responses to reward were more robust in individuals who carried genes resulting in higher levels of brain dopamine. The differences in response strength appeared in specific regions of the brain that function in anticipation and receipt of reward. Finally, each gene added to the effect of the other, so the response to either anticipation or reward was stronger when both genes conveyed a higher dopamine level.

This study identified individual and combined effects of the genes for COMT and DAT1 in specific brain regions involved in the anticipation and receipt of reward. The work suggests that the contribution of these genes to risk of certain mental disorders may be at least in part a function of their impact, through changes in dopamine, on the brain's reward system. Genes that individually have subtle effects on behavior and personality could, in the context of other genes and the environment, play a role in vulnerability to conditions affecting mental health. The research was done by investigators in NIMH's intramural research program, led by Drs. Jean-Claude Dreher and Karen Berman.

The work suggests how medications that target the action of COMT or DAT1 to alter dopamine function might be of help in treating individuals with mental health conditions in which dopamine plays a role. Knowledge of which gene variants a person has could be used as a guide to suggest whether altering dopamine activity could be of benefit.

Reference

Dreher, J.-C., Kohn , P., Kolachana, B., Weinberger, D.R., and Berman, K.F. Variation in dopamine genes influences responsivity of the human reward system. PNAS. 2009 106(2):617-622.