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D. Savage, P. Richter, M. Meade, J. M. Shull, E. B. Jenkins, G. Sonneborn and H. W. Moos in Astrophysical Journal, Supplement Series, Vol. 146, No. 1, pages 165–208; May 2003. com SCIENTIFIC AMERICAN COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. 47 INNER WORLD of people with schizophrenia is often confused, punctuated by alien voices, paranoia and illogical thoughts. Decoding Schizophrenia A fuller understanding of signaling in the brain of people with this disorder offers new hope for improved therapy COOP PHOTO ART COLLECTIVE By Daniel C.

Some reports show that people with schizophrenia have fewer NMDA receptors, although the genes that give rise to the receptors appear unaffected. If NMDA receptors are intact and present in proper amounts, perhaps the problem lies with a flaw in glutamate release or with a buildup of compounds that disrupt NMDA activity. Some evidence supports each of these ideas. For instance, postmortem studies of schizophrenic patients reveal not only lower levels of glutamate but also higher levels of two compounds (NAAG and kynurenic acid) that impair the activity of NMDA receptors.

We and others are therefore exploring alternative avenues. Molecules that slow glycine’s removal from brain synapses— known as glycine transport inhibitors— might enable glycine to stick around longer than usual, thereby increasing stimulation of JANUARY 2004 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. NMDA receptors. Agents that directly activate “AMPA-type” glutamate receptors, which work in concert with NMDA receptors, are also under active investigation. And agents that prevent the breakdown of glycine or D-serine in the brain have been proposed.

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