The overall goal of this proposal is to advance current understanding regarding the mechanisms that mediate how second trimester maternal infection and peri-natal hypoxia may increase SZ susceptibility. The specific aims of this study are to leverage the unique strengths of the ALSPAC so as to test the inter-relationships between obstetric complications, serum immune biomarkers and phenotypic features of SZ (i.e. childhood behavioral disinhibition and psychotic symptoms). Our hypothesis is that these in utero stressors activate the immune system resulting in persistently elevated serum cytokines, increased behavioral disorders and psychotic symptoms in the offspring. The primary statistical analytic approach to test these inter-relationships will use path analysis or related methods. Regression models will estimate the direct, indirect and total effects of obstetric complications and of serum immune markers on phenotypic features of SZ (psychotic symptoms and behavioral disinhibition).

Exposure variables:

? Maternal infections during pregnancy (e.g. influenza, rubella)

? Peri-natal hypoxia (e.g. umbilical cord around neck, prolonged labor, baby hypoxic requiring resuscitation); vaginal bleeding during pregnancy, placenta abruptio

? Questionnaires of mothers (32 weeks gestation and 8 weeks)

? Obstetric clinical records at time of delivery of the child

Outcome variables:

? interluekin-6 (child); C-reactive protein (child)

? IGFI (maternal); IGFII (maternal); IGFBP3 (maternal)

? Teacher ratings of child's behaviors (Child's Behaviors & Abilities questionnaire at Year 3 and The Developing Child questionnaire at Year 6)

? Mother ratings of child's behaviors (Strengths & Difficulties Questionnaire at 4 yrs, 7 yrs, more yrs?)

? Go/No-Go behavioral measures at age 17 yrs

? Psychotic symptoms (PLIKS-Q at ages 11, 13, 14 and 16 yrs)

Confounding variables:

? Low socioeconomic status

? Immunological disorders in mother or child

? History of schizophrenia in the mother.