Mice with specific genetic mutations exhibit behavior similar to human psychosis, report UT Southwestern Medical Center at Dallas researchers, providing further support to the notion of a genetic link to schizophrenia.
The researchers genetically engineered mice with a mutation in the gene NPAS3, a mutation in the gene NPAS1 or a mutation in both genes. Both genes encode proteins that switch other genes on and off in brain cells.
“These mice display certain deficits that are potentially consistent with schizophrenia,” said Dr. Steven McKnight, chairman of biochemistry at UT Southwestern and senior author of the study that will appear in an upcoming issue of the Proceedings of the National Academy of Sciences and is to be posted online this week.
“It’s too early to tell whether the abnormal behavior we observed in these mutated mice can be directly connected with human disease. On the other hand, we find it intriguing that members of a Canadian family carrying a mutation in the human NPAS3 gene have been reported to suffer from schizophrenia.”
Normal mice in a pen will climb over each other and interact, but the mice with the genetic mutations fail to socialize in this way. Instead, the mutants dart about wildly, avoiding interaction with their normal siblings.
In addition, the mutant mice do not have a normal startle response, and have a distinct reduction of a protein called reelin in their brains. Other researchers have shown in postmortem examinations of the brain tissue of schizophrenics that these patients have a reduction in reelin, said Dr. McKnight.
Schizophrenics also have problems socializing and often have enhanced physical activity, similar to that of the mutant mice. An impaired startle response, Dr. McKnight said, also may lead to a schizophrenia diagnosis.
More than 2 million Americans are affected by schizophrenia, according to the National Institute of Mental Health. The illness may impair a person's ability to manage emotions, interact with others and think clearly. Symptoms include hallucinations, delusions, disordered thinking and social withdrawal. Most schizophrenia patients suffer chronically or episodically throughout their lives, and one of every 10 people with schizophrenia eventually commits suicide.
“We recognize that the connection of our study to human psychosis or schizophrenia is very tenuous,” Dr. McKnight said. “It’s difficult to draw direct parallels between the simple behavioral abnormalities observed in the mutant mice and the complex, delusional cognitive defects that characterize human schizophrenia. Our results may turn out to have nothing to do with schizophrenia, or they could point to something more substantial.”