October 24, 1997
Media Contact: Nancy Volkers
The following presentations were among those made at the Stanley Neurovirology Laboratory's Third Annual Symposium on the Neurovirology and Neuroimmunology of Schizophrenia and Bipolar Disorder, held in Bethesda, Md. The Stanley Laboratory is based in the Department of Pediatrics at the Johns Hopkins Children's Center.
Frances Yee and colleagues at the Stanley Neurovirology Laboratory have found that four sequences of virus-associated RNA are found at higher levels in the brains of people with schizophrenia or bipolar disorder, compared with people with no history of psychiatric illness.
One RNA sequence, found at significantly higher levels in schizophrenic and bipolar patients, codes for a protein nearly identical to a protein that regulates DNA activity.
A second sequence, found at significantly higher levels in schizophrenic patients, codes for a protein similar to one of the proteins in avian reticulosis virus, which infects birds.
Two other RNA sequences code for proteins similar to proteins found in primate viruses. These sequences were found at significantly higher levels in bipolar patients.
Researchers at the Stanley Neurovirology Laboratory at Johns Hopkins have found higher levels of interleukin-2 receptor in the cerebrospinal fluid of patients with schizophrenia and bipolar disorder, compared with controls with no history of psychiatric illness. Patients with higher levels of the receptor were also more likely to have committed suicide. Linda Bobo and colleagues are currently analyzing the effects of medication, time of death, and smoking status on the levels of the IL-2 receptor to pinpoint possible confounding factors.
Researchers at the Washington State University School of Medicine have initiated a study of tamoxifen in the treatment of acute mania. Preliminary results suggest that this compound, more commonly known as an anti-cancer agent, has anti-manic properties as well. Husseini K. Manji and colleagues previously found that chronic administration of either lithium or valproate in rats reduces activity in an enzyme pathway that helps regulate neurotransmission. Because tamoxifen can also inhibit this pathway, it was chosen as a possible therapeutic agent.
Researchers at University College, Cork, Ireland, and the United Medical and Dental School of Guy's and St. Thomas', London, examined the levels of an interleukin 2 receptor in schizophrenic patients and their first-degree relatives. At all stages of illness, patient receptor levels were higher than control levels. Also, IL-2 receptor levels were higher in acutely ill patients than in patients with a more chronic phase of illness. Fiona Gaughran and colleagues also found a trend towards higher receptor levels in the mothers of patients compared with other first-degree relatives. This suggests that these women have enhanced immunoreactivity, providing circumstantial evidence that a component of the genetic link in schizophrenia may be at the level of the immune system.
Researchers at the New York State Psychiatric Institute examined the risk of affective psychosis requiring hospitalization after the 1957 influenza epidemic in Holland. Alan S. Brown and colleagues found that males exposed to influenza in the sixth month of gestation had a twofold risk of affective psychosis (RR=1.78, 95% CI 1.12, 2.82). They found no such association in females.
Researchers from the Stanley Research Unit at St. John of God Adult Psychiatric Services and the Health Research Board, Dublin, examined variation in the admission patterns of schizophrenia and affective disorder. Using data from all individuals admitted in the years 1989-94 with a diagnosis of first episode of schizophrenia or affective disorder, Mary Clarke and colleagues found significant seasonal variation in the monthly admission patterns of both conditions, with summer peaks. In July there were 12% more schizophrenia admissions and 17% more mania admissions than in any other month.
Researchers from the Fukushima Medical College, Hamamatsu University School of Medicine, Tokyo, found T-cell responses to Borna virus proteins in 10% of schizophrenic patients, 13.3% of patients with mood disorders and 6.7% of blood donors. Antibody to a Borna virus protein was detected in 3.6% of schizophrenic patients, 11.4% of mood disorder patients and 0% of blood donors. Borna virus RNA was detected in 7.8% of schizophrenic patients, 13% of mood disorder patients and 0% of blood donors. Yasuhide Iwata and colleagues suggest that these responses are due to either Borna virus infection or cross-reactivity to an unknown antigen. Borna virus was first discovered in horses in Borna, Germany and causes a fatal neurological disease in these animals.
Researchers from the Tokyo Institute of Psychiatry searched for Borna virus RNA coding for two different proteins in the brain tissue of schizophrenics and controls. Kazuhike Ikeda and colleagues found RNA for one protein in 3 of 43 (7%) controls and 5 of 23 (28%) schizophrenic patients' brain tissue. RNA for the second protein was found in 1 of 43 (2%) controls and 3 of 23 (13%) schizophrenic patients. Both RNAs were found in one schizophrenic individual and one control.
Researchers from Finland, the U.K., and Sweden used data from the 1966 birth cohort in Northern Finland to study the effects of central nervous system (CNS) infections on the subsequent risk of schizophrenia and other psychoses. Peter Jones of the University of Nottingham presented the results. The group found that people who had a viral CNS infection during childhood were nearly five times more likely to be diagnosed with schizophrenia than those who had not been virally infected. Those who had a bacterial CNS infection were seven times more likely to be diagnosed with other psychoses.
Of 11,017 subjects alive at 16 years, 102 of them had a viral infection during childhood, 43 a bacterial infection. Seventy-six had been diagnosed with schizophrenia and 53 with some other psychosis. Four patients diagnosed with schizophrenia had a history of viral CNS infection, and two patients diagnosed with other psychoses had a history of bacterial infection.
The odds ratio of schizophrenia after viral CNS infection was 4.8 (95% CI 1.6,14.0), the other significant risk factors being IQ <85, perinatal brain damage, and male sex. Odds ratio of other psychoses was 6.9 (95% CI 1.4, 32.8) after bacterial CNS infection, the other risk factors being IQ <85 and severe hearing defect.
The Johns Hopkins Children's Center is the children's hospital of The Johns Hopkins medical institutions. Maryland's most comprehensive acute-care hospital for children, the center, with its 177-bed hospital and more than 40 divisions and services, treats some 8,000 inpatients annually, with more than 64,000 outpatient visits.