Study suggests new schizophrenia cure

A potential new treatment for cognitive impairments in schizophrenia may put an end to the suffering of patients diagnosed with this psychiatric disorder.

A recent study by Pitt researchers investigates the activation of a special type of neurotransmitter receptor called the glutamate receptor. Researchers suspect that by changing this receptor, chemical reactions in the brain can be carried out normally.

The authors of this study, which was published on Oct. 1 in Biological Psychiatry, are Lucas Lecourtier, professor of neuroscience at the University of Pittsburgh; Houman Homayoun, University of Pittsburgh graduate medical trainee; Gilles Tamagnan, director of laboratory research and development at the Institute for Neurodegenerative Disorders; and Bita Moghaddam, professor of neuroscience at the University of Pittsburgh.

Schizophrenia is a mental illness that manifests three categories of symptoms: positive, negative, and cognitive. According to the World Health Organization (WHO) website, schizophrenia affects about 24 million people worldwide.

Positive symptoms of schizophrenia include hallucination and excessively peculiar behavior. Negative symptoms refer to the absence of normal behavior, such as disregard towards personal care and social withdrawal.

According to a news release, cognitive symptoms, which are the focal point of this study, are associated with “the inability to function socially and at work, due to impairments in attention, memory, and problem-solving.”

Schizophrenia usually attacks young individuals who are at the onset of adulthood. Studies in the past have shown that schizophrenia is a treatable ailment, though stages of schizophrenia are difficult to assess due to the psychological and emotional individuality of human beings.

“Positive, negative, and cognitive symptoms must be present for an individual to be diagnosed with schizophrenia.

“The major focus of our study is on the brain pathways located in the prefrontal cortex, the anterior section of the brain which controls the cognitive abilities of the mind,” said Bita Moghaddam, who is the corresponding author of the study.

According to the study, the possible cure suggests manipulating the neurotransmitter glutamate in a way that chemical reactions in the prefrontal cortex can be “normalized.”

This means that the chemical levels that have reached an abnormal degree during schizophrenia can be stabilized.

The abnormalities in the prefrontal cortex that trigger schizophrenia can be regularized in two steps. First, researchers must prevent the NMDA subtype of the glutamate receptor from being activated. Second, researchers must activate a different type of glutamate receptor called the metabotropic glutamate 5 receptor (mGluR5), by using the drug 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl), or CDPPB.

Moghaddam said, “It is the cortical cells which are actually responsible for the abnormality in the prefrontal cortex that leads to schizophrenia. Our hypothesis proposes that the interaction between different regions of the brain is largely dependent on glutamate, which acts as a chemical messenger.

“The normalization in the prefrontal cortex, which is home to the cognitive impairments in schizophrenia, is a promising therapeutic solution.”

Current treatment for schizophrenia, which involves blocking the neurotransmitter dopamine by blocking the dopamine receptors, not only “generates harmful side effects such as diabetes, weight gain, and dysphoria, but profoundly affects motor movement, which may even trigger the onset of Parkinson’s disease,” Moghaddam said.

Related experiments have shown positive results in rats. The researchers believe that as it has exhibited in these smaller mammals, their treatment may reflect improvement in humans affected by schizophrenia.

John H. Krystal, who is Editor of Biological Psychiatry and affiliated with Yale University School of Medicine and the VA Connecticut Healthcare System, stated in a news release, “These exciting new data provide important new evidence supporting the testing of mGluR5-stimulating medications for the treatment of schizophrenia, particularly cognitive deficits associated with impairments in the function of the prefrontal cortex.

“It would be very interesting to know whether this class of medication reduces the transient impairments in cognitive function associated with the administration of NMDA receptor blockers to humans.”

While the authors of this study intend to perform tests on the clinical implications of their hypothesis, they back its significance due to the visible regulation of cognitive deficits in the prefrontal cortex of rats caused by the activation of mGluR5.

“It shows that in an awake, behaving mammal (as opposed to in tissue cultures or similar preparations), activation of these receptors has a normalizing effect on the spontaneous activity of prefrontal cortex neurons,” Moghaddam said in a news release.

The results of this new study not only provide hope to suffering patients of schizophrenia, but they also suggest a cure which is free from adverse affects and can be implemented from the early onset of the disease.