NEW YORK (Reuters Health) - Dysbindin-1 levels are frequently reduced in terminal fields of intrinsic, glutamatergic connections in the hippocampal region of the brain in patients with schizophrenia, research indicates. And these alterations may contribute to the cognitive deficits seen in schizophrenic patients.
“Only very recently has schizophrenia been associated with variations in specific, named genes,” Dr. Steven E. Arnold of the University of Pennsylvania School of Medicine in Philadelphia told Reuters Health. Of the specific genes, the association with dysbindin is “the most robust so far, having been replicated in at least 12 different populations around the world,” he said.
Dysbindin is a novel protein first identified in muscle but also present in the brain as well as other body tissues. The function of dysbindin in the brain has yet to be firmly established.
Dr. Arnold’s team examined dysbindin-1 protein levels in postmortem brain tissue from people with schizophrenia and compared the findings with those from individuals without a history of mental illness. Contrary to expectations, they noted a “surprisingly frequent and marked decrease” in the amount of dysbindin in the hippocampus of schizophrenic patients compared to controls, Dr. Arnold reported.
Specifically, “73% to 93% of cases in two schizophrenic populations displayed presynaptic dysbindin-1 reductions averaging 18% to 42% at hippocampal formation sites,” the team reports in the May 1st issue of The Journal of Clinical Investigation.
Dysbindin-1 levels were highly inversely correlated with VGluT-1, the main glutamate transporter protein important for neurotransmission in the hippocampus.
“Abnormalities in dysbindin and associated glutamate neurotransmission,” Dr. Arnold explained, “would disrupt the functional circuitry of the hippocampus and lead to the learning and other cognitive deficits that are so much a part of schizophrenia and the principal cause of disability in people with the illness.”
Source: J Clin Invest 2004;113:1353-1363. [ Google search on this article ]
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