A study in youth who are missing part of a chromosome is further implicating a suspect gene in schizophrenia. Youth with this genetic chromosomal deletion syndrome already had a nearly 30-fold higher-than-normal risk of schizophrenia, but those who also had one of two common versions of the suspect gene had worse symptoms. They were more prone to cognitive decline, psychosis and frontal lobe tissue loss by late adolescence, when schizophrenia symptoms begin to emerge, found the study, which was funded by the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) and the National Institute on Child Health and Human Development (NICHD).

The gene version appeared to worsen symptoms of the deletion syndrome by chronically boosting the chemical messenger dopamine to excessive levels in the brain's executive hub, the prefrontal cortex, during development. The study is the first to show the long-term effects of the dopamine-regulating gene in a disorder related to schizophrenia, say Drs. Allan Reiss, Doron Gothelf, Stanford University, and colleagues at the University of Geneva, who report on their findings in the November 2005 issue of Nature Neuroscience.

"It's not that there's a good or bad version of this gene," explained NIMH director Thomas Insel, M.D. "Either version can be an accomplice, via interactions with other genes and environmental factors, in creating a dopamine imbalance that disturbs information processing. In this case, one version conspired with a rare mutation to produce too much dopamine. In other cases, the other version may tip the balance in the opposite direction."

Antipsychotic drugs used to treat schizophrenia work, in part, by correcting a dopamine imbalance in the prefrontal cortex, seat of motivation, learning in response to reward, and working memory -- functions impaired in schizophrenia. Previous studies have found and the current study confirms that optimal cognitive functio
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
23-Oct-2005

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