[D.sub.1] Receptors May Hold Key To Schizophrenia Outcome.

TORONTO -- Identifying patients with increased dopaminergic [D.sub.1] receptor levels may allow clinicians to better predict prognosis for the approximately 45 million people worldwide with schizophrenia, Dr. Anissa F. Abi-Dargham said at the annual meeting of the Society of Nuclear Medicine. Identifying the role of the receptors in schizophrenia also may lead to targeted drug therapies.

Using a new tracer that has permitted researchers to view activity in the frontal cortex for the first time, Dr. Abi-Dargham of Columbia University, New York, and her colleagues studied 16 medication-free patients with schizophrenia. Seven of the participants were drug naive, and nine had previous treatment. A control group of 14 people were matched for age, ethnicity, gender, parental socioeconomic status, smoking and left- or right-handedness.

Study participants who had the highest dopaminergic [D.sub.1] receptor levels in this part of the brain performed the worst on a standard test of working memory All participants received a PET scan of their brain activity following injection of a new radiotracer, NNC112, and after taking the n-back task, which is a common test of working memory.

Dr. Abi-Dargham and her associates discovered a significant increase in dopamine receptor binding potential in the brains of people with schizophrenia, compared with controls.

Participants with schizophrenia also performed worse on the n-back test in proportion to the increased dopamine [D.sub.1] receptor levels shown on their scan.

Interestingly, increased [D.sub.1] receptors were not found to be a global phenomenon. The increase was observed only in the dorsolateral prefrontal cortex--the region of the brain that is responsible for thought, recognition, perception, and working memory.

"Dopamine in the frontal cortex has been shown to be very important," Dr. Abi-Dargham. said at a press briefing. "Schizophrenia patients are very deficient in working memory, [which] inhibits them from learning new things and from performing their jobs well."

The higher levels of dopamine receptors observed in people with schizophrenia are believed to be related to a deficit in dopamine transmission, resulting in upregulated [D.sub.1] receptors. [D.sub.1] receptors mediate the action of the neurotransmitter.

"Patients with schizophrenia have an abnormally high number of [D.sub.1] receptors. This may indicate that the brain is trying to compensate by increasing the [D.sub.1] receptors in this region of the brain," she said.

Postmortem studies have suggested such a deficit in dopamine innervation in the prefrontal cortex. The study results have important implications for drug development, Dr. Abi-Dargham said. "Hopefully, this finding will lead to selective treatments--a [D.sub.1] against--to reverse cognitive impairments in people with schizophrenia and improve their long-term outcome."

The study was supported by the National Alliance for Research on Schizophrenia and Depression, the National Institute of Mental Health, the Charles F. Dana Foundation, and the Lieber Center for Schizophrenia Research.