( berg Weinberger and colleagues in the ...)Common gene version optimizes thinking -- but with a possible downside

Previous studies in animals over two decades, most notably by Nobel Laureate and NIMH grantee Paul Greengard, M.D., Rockefeller University, had established that DARPP-32 in the striatum switches streams of information from multiple brain chemical systems for processing by the cortex. Both the neurotransmitter that it works through, dopamine, and the chromosomal site of its gene have been implicated in schizophrenia.

"Although several groups have looked for possible clinical relevance of DARPP-32, they have not met with great success," noted Greengard. "This study shows a strong connection between this molecule and human cognition -- and perhaps with schizophrenia."

"These first glimpses of DARPP-32 at work in the living human brain build on a quarter century of investigations by Greengard's team that ultimately linked this pivotal protein to depression and substance abuse as well as to schizophrenia," added NIMH Director Thomas Insel, M.D.

To understand DARPP-32's role in the human brain, the NIMH researchers used genetic, structural and functional magnetic resonance imaging, and post-mortem techniques to identify the human gene's variants and their functional consequences. Seventy five percent of subjects had the most common version of the gene, which boosted circuit activation, structural and functional connectivity and performance on thinking tasks, likely by increasing gene expression. In 257 affected families, people with schizophrenia were more likely to have this common version of the DARPP-32 gene.
'"/>

Source:NIH/National Institute of Mental Health