Viral exposure boosts schizophrenia risk.

Viral Exposure Boosts Schizophrenia Risk

For about a month in the fall of 1957, Helsinki, Finland, was swept by a serious Type A2 influenza virus epidemic that is estimated to have infected two-thirds of the population. Thanks to the meticulous record-keeping of the Finnish government, researchers now have established that people who were exposed to the worldwide epidemic while in their second trimester of fetal development have an increased risk of hospitalization for schizophrenia.

"A basic risk for schizophrenia seems to occur when there is some kind of fetal trauma during the second trimester,' says psychologist and research director Sarnoff A. Mednick of the University of Southern California in Los Angeles. "It is not so much the type of stress as it is the timing of stress during gestation which is critical in determining the risk.'

But, importantly, he and his colleagues report they have found a link between second-trimester exposure to a specific virus and the adult diagnosis of schizophrenia. Longstanding theories of an "infection connection' in some cases of schizophrenia have generated more debate than data (SN: 11/30/85, p.346). The Finnish study, which will appear later this year in ARCHIVES OF GENERAL PSYCHIATRY, was generated by the researchers' ongoing, 24-year study of Danish children with schizophrenic mothers. Children who developed schizophrenia in adulthood and had an excess of birth complications also tended to have been born during periods of increased viral infections (January, February and March) in crowded Copenhagen.

For the county encompassing Helsinki, the investigators tracked all children born in the nine months immediately followint the 1957 epidemic who were hospitalized before the age of 26 in one or more of the county's eight psychiatric facilities. These 216 "index' individuals were compared with 1,565 "control' children born in the same county in the corresponding months of the previous six years, and who were hospitalized for psychiatric disorders before 26 years of age.

Nearly 36 percent of the index patients exposed to the epidemic during their second trimester of fetal development were diagnosed as schizophrenic by Finnish psychiatrists. In contrast, about 22 percent of both control patients and index subjects exposed to the epidemic in the first or third trimester of fetal development received diagnoses of schizophrenia; the rest had a variety of psychiatric diagnoses. The "second-trimester effect' held for both males and females, and independently in each of several of the psychiatric hospitals.

Moreover, for the entire Helsinki population, the rate of hospital diagnoses of schizophrenia per 1,000 Helsinki live births for second-trimester exposures was around I percent, twice the rate for first- and third-trimester exposures.

There is no direct evidence that pregnant women actually sufferred a viral infection during the epidemic, notes Mednick, and psychiatric admissions beyond 26 years of age have not been examined. Nevertheless, he says, the study adds to "sparse evidence' implicating other second-trimester disturbances with an increased risk of adult schizophrenia. For instance, Finnish researchers previously found that when pregnant women learned of their fathers' deaths during the second trimester, the offspring later showed an elevation in psychotic disorders including schizophrenia.

Infections and other disturbances during the second trimester may interfere with the migration of brain cells to structures in the cortex, the brain's outermost layer, says Mednick. A combination of these influences and a genetic predisposition may produce different forms of schizophrenia, he adds. The Danish study has identified birth complications, poor parental supervision and placement in public institutions as additional risk factors.

Further work needs to examine whether second-trimester vulnerability occurs over a limited period of perhaps a few days, says Mednick. He plans to repeat the influenza study in Denmark, where extensive population data are also available.