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Why People With Schizophrenia Have Lower Rates Of Cancer: New Clues

ScienceDaily (Dec. 9, 2007) — A series of studies presented December 8 at the American College of Neuropsychopharmacology (ACNP) annual meeting elucidates evidence that there is a genetic link between schizophrenia and cancer, providing a surprising possible scientific explanation for lower rates of cancer among patients with schizophrenia -- despite having poor diets and high rates of smoking -- and their parents.

Researchers at the National Institute for Mental Health (NIMH) emphasize that many of the genes associated with schizophrenia are the same as the genes associated with cancer, but that the cells that have these genes use them in opposite ways in the two disorders. While cancer results from changes in the genes that cause cells to go into metabolic overdrive and multiply rapidly, those same genes cause cells in schizophrenia to slow to a crawl.

"We found that many of the same genes are involved in schizophrenia as in cancer, but in a yin and yang way. This will provide critical insight into the molecular structure of schizophrenia," said lead researcher and ACNP member Dr. Daniel Weinberger of NIMH. Some of the genes showing this yin-yang effect include NRG1, AKT1, PIK3, COMT, PRODH and ErbB4. While these genes can't be used to predict exactly who will develop these diseases, Dr. Weinberger says they can be used to help determine risk.

Dr. Amanda Law of the University of Oxford, who heads one of the teams working at the NIMH, explored specific genetic pathways that cells use to make basic decisions about their development and their fate.

"This is about basic decision making by cells--whether to multiply, move or change their basic architecture," says Dr. Law. "Cancer and schizophrenia may be strange bedfellows that have similarities at the molecular level. The differences lie in how cells respond to external stimuli: in cancer the molecular system functions to speed up the cell and in schizophrenia the system is altered in such a way that causes the cell to slow down." Law adds that selective targeting of these pathways may be a potential target in developing treatments for schizophrenia.

"It's very curious that a brain disorder associated with very complicated human behavior has at a genetic and cellular level a striking overlap with cancer, a very non-behavior related disorder. Understanding these pathways might provide us with some new strategies for thinking about cancer," said Dr. Weinberger.

Dr. Weinberger added that future research involves using this information to search for therapeutic insights that can reverse these processes, with implications not only for treatment of schizophrenia, but also maybe for cancer as well.

An estimated two million Americans have schizophrenia, a biological condition that affects a person's ability to think clearly, distinguish reality from fantasy, to manage emotions, make decisions and relate to others. The World Health Organization has identified schizophrenia as one of the ten most debilitating diseases affecting humans.

Adapted from materials provided by American College of Neuropsychopharmacology.

Daniel E.
Cancer Drug Relieves Some Schizophrenia Symptoms in Mice
By Rick Nauert, Ph.D.
July 21, 2011

Researchers have uncovered a molecular pathway that is altered during the onset of schizophrenia. They then used a cancer drug currently in advanced clinical trials to reduce symptoms of the illness in mice.

Investigators believe the finding may one day lead to new pharmacological approaches for schizophrenia...

According to experts, a protein called Cdk5 is necessary for proper brain development. The creation of Cdk5 results, in part, by the presence of an enzyme in the brain, called p35.

In a study of human post-mortem brains, there was approximately 50 percent*less p35 in the brains of patients who had suffered from schizophrenia.

These molecular changes were then modeled and monitored in mice that had been modified to contain a comparable reduction in the p35 enzyme.

As a result of this reduction in p35, the mice showed a reduction in synaptic proteins – important in maintaining neural connections – and displayed symptoms associated with schizophrenia, including learning impairments and inability to react to sensory stimuli.

Understanding this signalling pathway and the impact of low levels of p35 is important in finding potential future treatments for the disease.

“We noted that the reduction in p35 affects the same molecular changes targeted by a cancer drug called MS-275, so we administered this drug to the mice. We were excited to find that MS-275 not only addressed the molecular changes but also alleviated the symptoms associated with schizophrenia,” Giese said.

“Our findings encourage the future exploration of these types of drugs for treating impaired cognition in schizophrenia.”

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The related class of drugs:

Histone deacetylase inhibitor - Wikipedia, the free encyclopedia
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