Cognitive Behavioral Therapy (3.11.03) - Psychologists are looking for ways other than medication to help people make sense of and deal with the voices they hear. A therapy adopted in Britain seems to have the answer.
Schizophrenic Brains (3.04.03) - It is a mental illness that robs victims of their thoughts. But now, there is a new understanding of schizophrenia from neuroscientists studying the brains of deceased patients, because researchers have shown that schizophrenic brain cells sprout abnormal connections that could be affecting the way schizophrenics think.
About one in a hundred people worldwide suffer from schizophrenia. Now neuroscientists may have found a gene variation that predisposes people to this brain disease. As this ScienCentral News video reports, it could lead to genetically targeted drugs for schizophrenia.
Schizophrenic Mice
Presently, schizophrenia affects 2.5 million Americans, and neuroscientists believe that this devastating brain disease is caused by problems with multiple genes. Now they are looking at genetically altered mice to help uncover those problematic genes.
Researchers at Massachusetts Institute of Technology (MIT) studied genetically altered mice that showed symptoms of schizophrenia. The mice were engineered to lack a protein called calcineurin.
According to Nobel laureate Susumu Tonegawa, "If you knock out this gene in the front part of the brain known as the forebrain, the animal looks fine, if you just casually observe them. If you subject these animals to a test, a maze test which was specifically designed to evaluate what is called working memory, we could demonstrate that this animal has severe deficits in this type of memory." Tonegawa is professor and director of the Picower Center for Learning and Memory at MIT, and Investigator of the Howard Hughes Medical Institute.
The normal mouse (left) found the chocolate chips quickly. The mutant mouse (right) did not.
The research team, which included Picower Center research scientist David J. Gerber, studied both normal mice and genetically engineered mice in mazes that had chocolate chips at the ends of each of eight tunnels. The normal mice were able to find the chocolate chips in one try. But the genetically engineered mice got confused. "They will even visit the same corridors they visited before, and be disappointed that the chip is not there," says Tonegawa. "So this is a type of memory, relatively short-term memory lasting several minutes, where the animal needs to fetch the food in a most effective manner. This is called working memory."
The researchers also subjected these "calcineurin knockout mice" to a variety of other behavioral tests and observed serious deficits, including attention deficits and social interaction deficits. "[In] all of these behavior tests, the calcineurin knockout mice exhibited significant and substantial impairment," says Tonegawa. "What is interesting is these are the behavior impairments well known among psychiatrists that human schizophrenia patients also display."
So the MIT team worked with another team led by Maria Karayiorgou, associate professor of genetics of mental illness at Rockefeller University in New York. They looked at the calcineurin gene in schizophrenic patients and their parents. "What we have shown is in the schizophrenia patients, a certain version of the calcineurin gene is transmitted from the parents," says Tonegawa. "Normal children receive different versions of the calcineurin genes."
Tonegawa suspects that many of the affected genes in schizophrenics may be associated with calcineurin, and that the gene may be a good target for designing effective drugs. "In principal, any one of a dozen genes in this calcineurin pathway can be impaired with the same final effect for schizophrenia patients. So this opened the door for identification of additional schizophrenia susceptibility genes in this pathway. This also provides…for new drug targets and hence, a new set of anti-psychotic drugs."
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