Potential New Drug Target for Schizophrenia Identified

According to a new study, people with schizophrenia have elevated levels of an enzyme called striatal-enriched tyrosine phosphatase (STEP). The study found antipsychotic medications commonly prescribed for schizophrenia reduce STEP levels in mice. The findings were presented at Neuroscience 2011, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.

Schizophrenia alters important molecules called N-methyl-D-aspartate receptors (NMDAR), which are necessary for communication between neurons. Previous studies showed that elevated levels of STEP equate to lower levels of NMDAR, which are required for many aspects of cognition.

To test whether antipsychotics improve cognition by reducing STEP in the brain, researchers led by Nikisha Carty, PhD, at Yale University, bred mice that do not have STEP, and gave them a drug that causes schizophrenia-like symptoms. After exposure to the drug, mice without STEP did not develop schizophrenia-like behaviors and showed increased amounts of NMDAR.

Antipsychotic medications, while effective, often cause adverse side effects and do not improve cognition. Moreover, many people show drug resistance. "Ultimately, these promising new results indicate that developing drugs that lower STEP levels may prove to be a more effective therapeutic strategy in the treatment of schizophrenia," Carty said.

The word "schizophrenia" is less than 100 years old. However the disease was first identified as a discrete mental illness by Dr. Emile Kraepelin in the 1887 and the illness itself is generally believed to have accompanied mankind through its history.

Written documents that identify Schizophrenia can be traced to the old Pharaonic Egypt, as far back as the second millennium before Christ. Depression, dementia, as well as thought disturbances that are typical in schizophrenia are described in detail in the Book of Hearts. The Heart and the mind seem to have been synonymous in ancient Egypt. The physical illnesses were regarded as symptoms of the heart and the uterus and originating from the blood vessels or from purulence, fecal matter, a poison or demons.

A recent study into the ancient Greek and Roman literature showed that although the general population probably had an awareness of psychotic disorders, there was no condition that would meet the modern diagnostic criteria for schizophrenia in these societies.

The research was supported by the National Institute of Mental Health.

Scientific Presentation: Sunday, Nov. 13, 3–4 p.m., Halls A–C

The evidence that schizophrenia is a biologically-based disease of the brain has accumulated rapidly during the past two decades. Recently this evidence has been also been supported with dynamic brain imaging systems that show very precisely the wave of tissue distruction that takes place in the brain that is suffering from schizophrenia.