MEDICINE A Pathway to Schizophrenia?

Schizophrenia and related mood disorders are thought to arise from a combination of genetic and environmental factors, but the identification of specific causative genes has been challenging. The disrupted in schizophrenia (DISC1) gene is on a short list of promising candidate susceptibility factors, but the function of its encoded protein has been unclear. Millar et al. (see the Perspective by Sawa and Snyder) now present evidence suggesting that the DISC1 protein modulates cellular cyclic adenosine monophosphate (cAMP) signaling through its physical interaction with the enzyme phosphodiesterase 4B and that disruption of this interaction may play a mechanistic role in the development of schizophrenia. Notably, cAMP signaling has previously been implicated in learning, memory, and mood in other experimental systems.

J. K. Millar, B. S. Pickard, S. Mackie, R. James, S. Christie, S. R. Buchanan, M. P. Malloy, J. E. Chubb, E. Huston, G. S. Baillie, P. A. Thomson, E. V. Hill, N. J. Brandon, J.-C. Rain, L. M. Camargo, P. J. Whiting, M. D. Houslay, D. H. R. Blackwood, W. J. Muir, D. J. Porteous, DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 310, 1187-1191 (2005). [Abstract] [Full Text]

A. Sawa, S. H. Snyder, Two genes link two distinct psychoses. Science 310, 1128-1129 (2005). [Summary] [Full Text]

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