Low birth weight (LBW) and hypoxia are among the environmental factors most reliably associated with schizophrenia; however, the nature of this relationship is unclear and both gene-environment interaction and gene-environment covariation models have been proposed as explanations. High-risk (HR) designs that explore whether obstetric complications differentially predict outcomes in offspring at low risk (LR) vs HR for schizophrenia, while accounting for differences in rates of maternal risk factors, may shed light on this question.
Studies into the central nervous system (CNS) of fetuses, newborns, and infants with a history of intrauterine infection or intoxication suggest a possibility for development of viral, bacterial, and fungal encephalitis and encephalomyelitis in utero. These conditions may resolve antenatally or persist for a number of years after birth, and may give rise to autoimmune nonspecific inflammation which is self-sustained and thus of long duration. A complex rehabilitation therapy for these conditions employs immunomodulators, which significantly increases its efficacy.