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Schizophrenia’s Slow Cells

Analysis of almost 1000 proteins in the stem cells of schizophrenia patients has indicated that their cellular machinery for making new proteins is reduced, with the rate of protein synthesis greatly impaired.

“Proteins are the workhorses of all cells and make up most of a cell’s structure and functions,” says Em/Prof Alan Mackay-Sim of Griffith University. “Cells live in a very dynamic environment and protein synthesis, which is so important for brain development, function and learning, is impacted by environmental and genetic factors.

“It is now becoming clearer that many small genetic variants are linked because they share control of cellular functions, in this case protein synthesis. If protein synthesis is altered even slightly, many cell functions would also be subtly changed. This could affect brain development and adult brain function in schizophrenia.

Mackay-Sim said the research, published in Translational Psychiatry (tinyurl.com/ns79wyl), “helps make sense of the rapid advances in genetics that have identified hundreds of risk genes for schizophrenia”.

The same issue of Translational Psychiatry reports contrasting findings from a second research collaboration involving Mackay-Sim that examined induced pluripotent stem cells (iPS) in people with schizophrenia. These iPS cells are genetically engineered from skin cells and stimulated to turn into stem cells resembling neural progenitor cells, which give rise to the brain in the developing human embryo.

When the proteins from iPS cells were analysed, the patients’ cells were found to have more protein-making machinery and also made proteins more quickly than cells in healthy controls.

“However, while on the surface this seems like a contradiction, the two studies support each other by showing that the regulation of protein synthesis is subtly disturbed in the cells of people with schizophrenia,” Mackay-Sim says. “The studies seem to show that the on/off switch for protein synthesis may be altered in different cells or at different life stages in schizophrenia. This provides many ways in which brain development and function is altered in schizophrenia, and many routes for the ways in which genes and the environment interact to cause schizophrenia.”