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Stephen L. Buka, ScD; Ming T. Tsuang, MD, PhD; E. Fuller Torrey, MD; Mark A. Klebanoff, MD; David Bernstein, MD; Robert H. Yolken, MD

Arch Gen Psychiatry. 2001;58:1032-1037.

Background  We tested the hypothesis that maternal infections during pregnancy are associated with the subsequent development of schizophrenia and other psychoses in adulthood.

Methods  We conducted a nested case-control study of 27 adults with schizophrenia and other psychotic illnesses and 54 matched unaffected control subjects (matched for sex, ethnicity, and date of birth) from the Providence, RI, cohort of the Collaborative Perinatal Project. We retrieved stored blood samples that had been obtained from these mothers at the end of pregnancy. These samples were analyzed for total class-specific immunoglobulins and for specific antibodies directed at recognized perinatal pathogens capable of affecting brain development.

Results  Maternal levels of IgG and IgM class immunoglobulins before the mothers were delivered of their neonates were significantly elevated among the case series (t = 3.06, P = .003; t = 2.93, P = .004, respectively, for IgG and IgM immunoglobulin-albumin ratios). Secondary analyses indicated a significant association between maternal antibodies to herpes simplex virus type 2 glycoprotein gG2 and subsequent psychotic illness (matched t test = 2.43, P = .02). We did not find significant differences between case and control mothers in the serum levels of IgA class immunoglobulins, or in specific IgG antibodies to herpes simplex virus type 1, cytomegalovirus, Toxoplasma gondii, rubella virus, human parvovirus B19, Chlamydia trachomatis, or human papillomavirus type 16.

Conclusions  The offspring of mothers with elevated levels of total IgG and IgM immunoglobulins and antibodies to herpes simplex virus type 2 are at increased risk for the development of schizophrenia and other psychotic illnesses in adulthood.

From the Harvard School of Public Health (Drs Buka and Tsuang), Harvard Medical School (Drs Buka and Tsuang), and Harvard Institute of Psychiatric Epidemiology and Genetics (Drs Buka and Tsuang), Boston, Mass; Stanley Research Laboratory (Dr Torrey), and Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development (Dr Klebanoff), Bethesda, Md; Children's Hospital Medical Center, Cincinnati, Ohio (Dr Bernstein); and the Stanley Division of Developmental Neurovirology, The Johns Hopkins School of Medicine, Baltimore, Md (Dr Yolken).

Reprints: Stephen L. Buka, ScD, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115.

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