Inside Out: Looking at schizophrenia’s inner chaos pg. 4
Using functional PET (positron emission tomography), a brain scanning technique, Meltzer and Dr. Robert M. Kessler, professor of Radiology and Radiological Sciences at Vanderbilt, have found that clozapine-like drugs produce a different pattern of dopamine receptor blockade in cortical and limbic (“emotional brain”) areas. This finding provides evidence that the delusions and hallucinations may be the result of excessive dopamine in the limbic system, while the cognitive impairment may be due, in part, to too little dopamine in the cortex, he says.
During the course of his studies with clozapine, Meltzer and his colleagues found that the drug improved some elements of cognitive function in schizophrenia patients. Confirmation of this first evidence that an antipsychotic drug could improve cognitive impairment changed the focus of the search for better drugs for schizophrenia, making cognition a primary and separate target.
Meltzer’s current research is designed to identify new treatments to further improve cognitive impairment in schizophrenia. Success, he believes, may lead to drugs to treat many forms of cognitive loss, including those due to aging and Alzheimer’s disease.
A shift in focus
A look inside the brains of schizophrenia patients shows that the structure is not dramatically changed by the illness. One subtle change is the decreased size of the frontal lobe in schizophrenia patients. Since the frontal lobe is the seat of many of the brain’s higher cognitive functions, it’s been a logical destination for schizophrenia researchers in search of aberrations, including Sohee Park, Ph.D., professor of Psychology and Psychiatry at Vanderbilt.
Park’s work draws on the contributions of the late Patricia Goldman-Rakic, Ph.D., a Yale University neuroscientist who pioneered current understanding of memory function and was the first to describe the order and structure of the frontal lobe.
When Park was working on her doctorate, Goldman-Rakic reported that monkeys with lesions in the frontal lobe were bad at tasks that required spatial working memory—the ability to remember the location of an object after a brief delay.
Park adapted Goldman-Rakic’s work in the primate model, designing a spatial working memory test for humans.
Park used the test to study performance of schizophrenia patients versus normal individuals and patients with bipolar disorder, and found that only those with schizophrenia had problems with the task. She expanded her studies to people with schizotypal personality disorder, or schizotypy, a milder version of schizophrenia often seen in first-degree relatives.
“As might be predicted,” Park says, “the performance of people with schizotypy falls in-between that of normal controls and people with the full-blown disorder.”
Monitoring the brains of those performing the task using a special scanning technique called functional magnetic resonance imaging, or fMRI, Park found that normal individuals have increased activity in a specific region of the frontal lobe—the convex shaped area on either side of the head, just above the temple, known as the dorso-lateral prefrontal cortex.
View Related Article:
Creativity and madness: are they linked?