No association between prenatal viral infection and depression in later life: a long-term cohort study of 6152 subjects

OBJECTIVE: Previous studies have suggested a role for prenatal viral infections in the etiology of schizophrenia; however, little is known about depression. We examined whether in-utero viral infections result in increased risk of depression in later life. METHOD: We identified a cohort (n = 3076) born between 1946 and 1980, whose mothers suffered known viral infections in pregnancy. Subjects were individually matched by birthdate, sex, and area of birth to another cohort (n = 3076) from the UK National Health Service Central Register (NHSCR). These 2 cohorts, one exposed to viruses prenatally, the other not known to have been exposed, were then followed-up to June 1996 by sending a morbidity questionnaire to their primary care physicians. This included specific items on affective disorders, schizophrenia, mental handicap (mental retardation), epilepsy, as well as other central nervous system disorders and specified physical illness, all coded according to the International Classification of Diseases, Ninth Edition. Death certificates were supplied by the NHSCR. A method for matched-pair cohort data calculated the relative risk and 95% confidence intervals for depression in the exposed and unexposed cohorts by varying type of viral exposure. RESULTS: The response to the questionnaire was high (85%). There was no overall increased risk for depression associated with viral exposure; a narrow confidence interval surrounded unity (RR = 1.0, 95% CI 0.8 to 1.2); effects for individual viral exposures were all scattered around unity. CONCLUSIONS: The results provide no support for the hypothesis that in-utero exposure to viral infection is associated with risk of subsequent nonpsychotic affective disorder. Further analyses on schizophrenia, bipolar disorder, and mental illness other than depression are required.