Envoronmental Pre- and Perinatal Influences in Etiology

A few specific pregnancy and perinatal factors were associated with the subsequent development of psychotic disorder, particularly schizophrenia, in early adult life. The association of small size for gestational age and bleeding during pregnancy with increased risk of early onset schizophrenia among males could reflect placental insufficiency.

In the search for the causes of schizophrenia, the preponderance of evidence suggests that genes play a substantial role in the etiology of the disorder. Based on the results from twin, family, and adoption studies, genetic influences account for approximately 80% of the disorder's etiology. Although schizophrenia appears to be a highly heritable disorder, it is clear that environmental factors also are involved.

Many environmental influences have been investigated as potential contributors to the disorder, such as family environment, socioeconomic status, and substance abuse; however, a repeatedly demonstrated environmental predictor of schizophrenia has been a history of obstetric complications (OCs). OCs constitute a fairly broad class of events, including any deviation from the normal course of pregnancy, labor - delivery, and the early neonatal period, such as low birthweight, prenatal maternal infection, and many others (discussed below).

Such complications are relatively common, occurring in the histories of approximately 20 - 30% of patients with schizophrenia and approximately 5 - 10% of the population overall. In this chapter, we provide an overview of the various OCs that have been linked to schizophrenia, discuss different explanatory models of how OCs operate within the etiology of the disorder, and discuss the potential mechanisms underlying two main classes of OCs associated with schizophrenia: prenatal infection and fetal oxygen deprivation.

Evidence from epidemiological and neuropathological studies indicates that pathogenic processes that culminate in the development of schizophrenia are initiated early in life. The neurodevelopmental hypothesis that schizophrenia has its origins in aberrant brain development receives support from the evidence of an association between obstetric complications and schizophrenia, especially schizophrenia with an early age of onset. However, there is still controversy concerning the specificity of this association for schizophrenia, the existence of specific risk factors, and the possibility of a bias in the literature towards publication of positive findings. In a recent hospital based case-control study of 107 schizophrenic patients with age of onset up to 45 years only aberrations in size at birth remained significantly associated with schizophrenia in a multivariate analysis.

We undertook the present nationwide Swedish study to examine the association between size at birth and other prenatal and perinatal factors and the risk of developing schizophrenia in early adult life. Additionally, we addressed the question of whether disturbance in prenatal development is specific to schizophrenia or whether it also occurs in affective and reactive psychoses.