Schizophrenia is a devastating chronic mental disorder that affects nearly 1 percent of the adult population. Previously, I’ve written about the positive and negative symptoms of schizophrenia, and about the possible causes of the illness.
As seems to be the case with many mental and physical disorders, the disorder’s origins are often thought to spring from multiple sources.
Something called the “two-hit hypothesis” suggests that people may have a genetic predisposition for a particular disorder followed by life experiences that contribute to their vulnerability to develop that illness.
Perhaps people with strong genetic predispositions would require little stress early in their lives to bring about the symptoms of the illness, while people with lower predispositions might need much more profound stress for the disorder to appear.
Thus, understanding both the genetic and life-experience factors that contribute to illnesses like schizophrenia is critical to advancing the treatment of these mental disorders.
Sometimes animal models are used as surrogates for human diseases. Creating an animal model for a medical disorder is much easier to do when the animal in question shares the same basic physiology as a human. In contrast, finding animal models for mental disorders is a much greater challenge, because mental processes involve perceptions, thoughts, moods, and behaviors.
A new study by Johns Hopkins researchers published online in the Proceedings of the National Academy of Sciences represents a major advance in the use of animal models to represent human psychiatric diseases.
Akira Sawa, M.D., Ph.D., and his colleagues developed genetically engineered mice with an abnormality in a human gene called the Disrupted-In-Schizophrenia-1 gene (DISC1), which is known to increase a person’s susceptibility to schizophrenia. They were able to produce a mouse strain having an incomplete, shortened form of the DISC1 protein that attaches to a normally formed protein. The combination interferes with the function of the normal protein.
As these genetically engineered mice matured, they had abnormal characteristics that paralleled certain features of human schizophrenia. They had enlarged and asymmetrical lateral ventricles in their brains, as seen with MRI scans. The mice also demonstrated hyperactivity, trouble finding hidden food, apathy, and small cognitive deficits.
The researchers do not claim to have discovered the cause of schizophrenia, but they believe that they have come closer to being able to show how a specific gene that confers vulnerability to a human mental illness, if duplicated in an animal species, could bring about similar behavioral and anatomical changes in the animal. This type of research ultimately could have important treatment implications.
