A new study offers the first physical evidence to validate the long-held idea that an increase in dopamine activity is responsible for the positive symptoms of schizophrenia.

The study, which looked at the role of dopamine and the dopamine D2 receptor in the brains of patients with schizophrenia, provides the first direct evidence from living human subjects that schizophrenia is associated with an overstimulation of dopamine receptors in the brain.

Researchers from Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute published their findings in the July 5 issue of Proceedings of the National Academy of Sciences (PNAS).

The researchers used radioactive tracers along with SPECT imaging techniques to visualize D2 receptor availability before and during pharmacologically induced acute dopamine depletion.

The researcher concluded that the percentage of receptors occupied by dopamine in the absence of any antipsychotic drug treatment is significantly higher in the brain of a patient with schizophrenia than in a matched individual with no history of any neurological, psychiatric, or serious medical illness.

In addition, after six weeks of treatment with antipsychotic therapy, the degree of reduction in symptoms, such as delusions, hallucinations, thought disorganization, and paranoia, is directly associated with the degree of disruption in dopamine regulation in the patient with schizophrenia. However, the researchers reported, the severity of social, emotional, and cognitive symptoms after drug treatment appears to be unrelated to the extent of dopamine dysregulation.

Significantly, the data show that overstimulation of the D2 dopamine brain receptor is present at the onset of the disease, prior to any treatment with antipsychotic medications.

In a commentary appearing in the same issue of PNAS, Philip Seeman, M.D., a professor of psychiatry and pharmacology at the University of Toronto, discusses the significance of the findings. According to Seeman, the report significantly "provides support for both an increase in the level of dopamine as well as an increase in the number of D2 receptors in schizophrenia, compared with control subjects."

Lead author Anissa Abi-Dargham, M.D., the Irving associate professor of clinical psychiatry at Columbia, and her colleagues commented that the significance of their work is that the "paradigm used here reveals D2 receptor occupancy by dopamine during the baseline scan—that is, in the absence of any pharmacologic intervention."

The authors pointed out that the next obvious step in researching schizophrenia is to unlock the cause of the increased levels of dopamine and D2 receptor activity. They suggest one hypothesis is an abnormal decrease of glutamate release in the brains of schizophrenic patients, causing a relative increase in dopamine.