This proposal addresses several problems with the fetal virus-adult schizophrenia research. 1. In almost all of the studies, an increased risk for schizophrenia is related to exposure to the epidemic rather than empirical evidence of an influenza infection. The one exception is our own Helsinki study, but the number of subjects for that study was small. In the context of a population of 5387 Finnish schizophrenics, we propose to determine whether recorded instances of influenza tend to segregate in the second trimester of gestation. 2. We do not know what changes in the fetus, attributable to the viral infection, increase risk for later schizophrenia. We are addressing this problem by examining the neurointegrative and neuromotor functioning of infants whose mothers have a serologically confirmed infection at a known time during gestation. 3. The virus-schizophrenia correlation does not establish whether influenza is the only infectious disease which may increase risk for later schizophrenia. We are examining the effect of a serologically-verified mycoplasma pneumonia infection during gestation on the neurointegrative functioning of the infant. 4. The influenza viral infection is a relatively specific """"""""cause"""""""". We attempted to determine whether we could detect a narrowly-defined resultant clinical syndrome. We found that the second-trimester infection produced schizophrenics with marked delusions and reduced levels of thought disorder. We propose to examine the brains of these schizophrenics with MRI to determine whether we can identify a similarly narrowly defined neuroanatomical disturbance underlying the specific clinical syndrome. 5. We propose to examine the possibility that the viral effect is due to antibody reactions to specific fetal brain tissues. We plan to immunostain second trimester fetal neural tissue with IgG and IgM class antibodies and attempt to determine which parts of the brain are recognized by these antibodies. Pilot work has implicated the hippocampus and the basal ganglia.

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National Institute of Mental Health (NIMH)
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Epidemiology and Genetics Review Committee (EPI)
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University of Southern California
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Schools of Arts and Sciences
Los Angeles
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Schiffman, Jason; Maeda, Justin A; Hayashi, Kentaro et al. (2006) Premorbid childhood ocular alignment abnormalities and adult schizophrenia-spectrum disorder. Schizophr Res 81:253-60
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