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Scientists discover possible test for schizophrenia

BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7280.192/a (Published 27 January 2001) Cite this as: BMJ 2001;322:192
  1. Judy Siegel-Itzkovich
  1. Jerusalem

    Israeli researchers may have found a way to diagnose schizophrenia by analysing white blood cells for signs of a chemical that is overactive in patients with the psychiatric condition.

    Psychiatrists may be able to give patients a simple blood test to determine at an early stage whether a patient has the disorder instead of observing behaviour for at least six months before diagnosing and treating it.

    The blood test, which has been patented but is not likely to be commercially available for several years, was proposed and tried on patients by Professor Sara Fuchs of the immunology department of the Weizmann Institute of Science in Rehovot and by graduate student Tal Ilani.

    Their study, carried out with help from colleagues at the Rambam Hospital in Haifa and the nearby Be'er Ya'acov and Tirat Hacarmel mental health centers, appears in last week's issue of the Proceedings of the Academy of Sciences of the USA (2001;98:625-8).

    The test could eventually lead to the development of better drugs for managing the chronic disorder, which affects about 1% of the population. Schizophrenia is characterised by disturbances in the person's emotional functioning, perception of reality, and thought processes. Among the symptoms are hallucinations, delusions, and the patient's feeling that he is “broadcasting thoughts” to other people or that others are doing the same to him.

    Because the biological basis of the disease is still a mystery and symptoms may be transitory (owing to the ingestion of hallucinogenic chemicals, trauma to the brain, epilepsy, brain injury, thyroid malfunction, or other causes), it cannot reliably be diagnosed until after six months of observed symptoms.

    Numerous research findings, said Professor Fuchs, suggest a possible connection between the disease and an excessive activity of dopamine—a neurotransmitter involved in communication between nerve cells in the brain.

    This activity is dependent, among other factors, on the number of dopamine receptors on the surface of nerve cells. In fact, postmortem studies of the brains of schizophrenic patients, as well as positron emission tomography of the brains of live patients, have suggested that the number of these receptors is increased in schizophrenia. Therefore, by measuring this number it may be possible to diagnose the disease.

    But Professor Fuchs noted that it is impossible to assess the number and location of dopamine receptors in the brains of live schizophrenic patients with adequate precision. She and her coauthor suggested that the way to get around this problem is to evaluate the presence of dopamine receptors on the surface of lymphocytes.

    The researchers thus compared blood samples taken from people with schizophrenia in local psychiatric hospitals with samples from healthy people. As identifying dopamine receptors on the surface of white blood cells is extremely difficult, the scientists focused on an earlier stage in receptor formation, the stage at which messenger RNA (mRNA) molecules in the cells convey the genetic information needed for making dopamine receptors from the cell nucleus to the ribosome, the small cellular “factory” where the receptors are manufactured.

    A statistical analysis showed that the blood of patients with schizophrenia contains on average 3.6 times more mRNA molecules of dopamine receptors of a particular kind (D3) than the blood of healthy people.

    The high levels were observed in patients treated with various drugs, as well as in patients who received no drugs. On the basis of these findings, the scientists proposed using the blood test determining the levels of mRNA that encode D3 receptors on the membranes of white blood cells as a test for schizophrenia.

    Professor Avi Weizman, a psychiatrist and researcher at Israel's Geha psychiatric hospital who has followed the Weizmann Institute's research, called the findings a breakthrough that could lead to the development of more receptor specific drugs with fewer side effects.

    “The research is very important, not only because it makes objective and early diagnosis realistic, but because it stresses the biological nature of schizophrenia and will thus help reduce the public stigma of the disease. But the test has to be tried on a larger number of patients—both treated and untreated—and show it is reproducible in all of them,” he said.

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