Adult Major Affective Disorder After Prenatal Exposure to an Influenza Epidemic

Background: We have previously reported an increase in schizophrenia diagnoses in a population exposed during the second trimester to the 1957 influenza epidemic. These basic findings together with a fair number of replications have been interpreted as supporting a neurodevelopmental contribution to the origins of schizophrenia. Recent neuroimaging findings suggest that affective illness may also have a neurodevelopmental origin. We examined the hypothesis that exposure to an influenza epidemic during the second trimester would increase the risk for adult major affective disorder.

Methods: The subjects had been exposed as fetuses to the type A2/Singapore influenza epidemic in greater Helsinki, Finland. Control subjects were born in the 6 years before the epidemic.

Results: We found a significant (P < .001) increase in the proportion of hospital diagnoses for major affective disorder for individuals exposed to the influenza epidemic during their second trimester of fetal development compared with control subjects (13% vs 2%). This second-trimester effect seems somewhat stronger in men (16% vs 2%) (P < .001), although the rates of major affective disorder in women (8% vs 3%) (P > .05) were similar. The second-trimester effect remained when we estimated population-based rates (2.1 vs 0.6 per 1000) (P < .05) of major affective disorder. Additional analyses revealed that the increase of major affective disorder among subjects in the index group who were exposed during the second trimester was due to a significant (P < .002) elevation of unipolar forms, although a similar though not significant (P > .05) elevation was observed for the bipolar forms of major affective disorder.

Conclusions: These data are consistent with the hypothesis concerning the possible neurodevelopmental contribution to the origins of some forms of major affective disorder, especially unipolar depressive disorder. These encouraging findings, if replicated, may suggest that some mental disorders may stem, in part, from a disturbance in the development of the fetal brain during the second trimester.