Schizophrenia Symptoms Linked to Enzyme
> 5/23/2008 9:24:27 AM

In past work, researchers from Johns Hopkins University School of Medicine have demonstrated a link between Alzheimer’s disease and the BACE1 enzyme, and they had theorized that blocking this enzyme might help prevent the onset of Alzheimer’s. In a new study, however, these researchers demonstrate that such actions may actually contribute to the development of schizophrenia. Their research with mice, which appears in the Proceedings of the National Academies of Sciences, establishes an association between the absence of BACE1 and the presence of social deficits that accompany schizophrenia.

To examine the influence on BACE1 on the development of schizophrenia, the researchers tested rodent social skills using normal mice and mice engineered to lack the enzyme. Typically, two mice meeting for the first time will be interested in each other, but they will show less interest during subsequent meetings, a process known as habituation. Mice missing BACE1 appeared to follow this pattern at first, but further testing revealed impairments in their social behavior. Initially, they showed interest in a mouse they had never met before and then lost interest when they were reintroduced to the same mouse later on. But when they were introduced to a second mouse for the first time, they showed no interest, an abnormal reaction described as a deficit in social recognition. Tellingly, these mice also developed other signs of schizophrenia, including cognitive impairments and hyperactivity triggered by a new environment. And when the researchers administered clozapine, an antipsychotic commonly used to treat schizophrenia, they observed some improvements in symptoms, a finding that further strengthened the observed connection between BACE1 and this debilitating psychiatric condition. Because these mice demonstrated multiple schizophrenia symptoms and responded to treatment, the researchers surmise that they may represent a new animal model for schizophrenia.

Many factors can influence the development of mental illness, and the researchers suggest that impaired functioning of BACE1 may boost the vulnerability to schizophrenia in some individuals. This enzyme may represent a new target for medications used to treat schizophrenia, and with a better understanding of its role in schizophrenia, researchers may be able to develop new and effective treatments to address certain symptoms, including social deficits. Individuals with schizophrenia often withdraw from the world around them, and the resulting social isolation can be detrimental to their well-being and can further worsen their disordered thoughts and behaviors. Treatment is crucial, and with the appropriate care, individuals with schizophrenia can improve their symptoms and their daily functioning.

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