Several neurological and psychiatric disorders, including schizophrenia, alcoholism, and Parkinson’s disease, are associated with changes in the brain that affect the nerves that communicate with each other through the naturally-produced chemical dopamine. One protein that is crucial for dopamine-mediated neuronal communication in animals is DARPP-32. However, very little is known about the function of this protein in humans.



In a study appearing online on February 8 in advance of publication in the March print issue of the Journal of Clinical Investigation, Daniel Weinberger and colleagues from the National Institutes of Health show that the gene that encodes DARPP-32 exhibits genetic variation. One particular variant that increased expression of the mRNA encoding DARPP-32 in the brain was associated with increased performance in a number of cognitive tests, including IQ and memory tests. This variant was also associated with changes in the structure and function of part of the brain known as the neostriatum, as well as changes in the ability of the neostriatum to communicate with the frontal lobe. Importantly, preliminary analysis indicated that this variant was associated with an increased risk of schizophrenia, although further studies will be necessary to confirm this association.

TITLE: Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition