Viruses, Fetal Hypoxia and Subsequent Schizophrenia: A Direct Test of Infectious Agents Using Prenatal Sera

VIRUSES,

FETAL HYPOXIA AND SUBSEQUENT SCHIZOPHRENIA: A DIRECT TEST OF

INFECTIOUS AGENTS USING PRENATAL SERA

S.L. Buka*,

R.H. Yolken, E.F. Torrey, M.A. Klebanoff, M.T. Tsuang. Department

of Psychiatry, Harvard Medical School, Boston, MA

There remains much debate

regarding the role in utero exposure to viruses and other

infectious agents in the etiology of schizophrenia. There are no

studies to date that provide a definite link between an

infectious agent and psychosis. Our follow-up work with the

Providence and Boston cohorts of the National Collaborative

Perinatal Project provides an unprecedented opportunity to

examine these topics. This study included over 16,000 pregnancies

enrolled during the 1960’s and followed prospectively from

the first prenatal visit through the age of seven. Maternal blood

samples were drawn during each trimester of pregnancy under

study, along with infant cord samples; these sera have been

well-maintained at NIH facilities. We have conducted a pilot

case-control study involving subjects from the Providence cohort.

We identified 35 subjects diagnosed with psychotic disorder and

70 control subjects with no history of major psychiatric

disorders, matched for age, race and gender. Three classes of

assays have been conducted, most using quantitative solid phase

enzyme immunoassays employing as little as 1 ul of serum. These

have included: 1) antibodies to specific infectious agents (e.g.,

influenza, Herpes simplex, toxoplasmosis); 2) indicators of

immune activation (cytokines); and 3) indicators of fetal

distress and anoxia (erthropoetin). Preliminary analyses indicate

a possible association of infectious, inflammatory, and hypoxic

events during pregnancy and the development of psychosis in adult

life.