What types of OCs are associated with Schizophrenia?

OCs have been linked to the etiology of schizophrenia since the 1960s when Lane and Albee (1966) first observed that birthweights of 52 patients with schizophrenia were lower than those of their siblings without schizophrenia. Despite the fact that the differences were relatively small (about 175 grams), and few of the schizophrenia patients had birthweights that were less than 2,500 grams (the criterion for low birthweight), this study raised the possibility that events during the very early stages of life may have longlasting neurobiological effects, potentially contributing to the causes of schizophrenia.

Since the 1960s dozens of articles have linked aberrant events during the pre- and perinatal periods to schizophrenia. Investigations into this area have taken many forms, such as following genetically at-risk individuals (e.g., offspring of patients with schizophrenia and unaffected siblings of patients with schizophrenia), comparing the prevalence of OCs in patients with schizophrenia and controls (often using maternal recall), and, last, taking advantage of population databases and registries containing detailed information about the pre- and perinatal periods, as well as information regarding psychiatric statuses. Given the variety of study procedures, the conflicting results from many of the investigations exploring the role of obstetric events in the etiology of schizophrenia are not surprising. For this reason, studies using population registries (e.g., in Scandinavia) have been especially useful in providing detailed, prospective obstetric information, in addition to having large enough samples to detect meaningful results.

Recent findings from population-based studies have had the added advantage of exploring molecular pathways in schizophrenia by examining stored maternal blood sera from the pre- and perinatal periods. For our purposes in this chapter, we briefly summarize the types of OCs that have been associated with schizophrenia; however, we focus on the more recent, population-based results, especially those using serological data.

Many OCs have been linked to schizophrenia and can grossly be divided into categories of complications during pregnancy, fetal and neonatal underdevelopment, and birth complications. A meta-analysis of eight population-based studies found that diabetes during pregnancy, birthweight less than 2,000 grams, emergency caesarean section, congenital malformations, uterine atony, rhesus variables (comprising rhesus [Rh] incompatibility, Rh-negative mother, Rh antibodies), fetal asphyxia, bleeding during pregnancy, birthweight less than 2,500 grams, preeclampsia, placental abruption, head circumference less than 32 cm, and nonspontaneous delivery all were associated with increased risk of schizophrenia. Beyond these eight studies, a large body of research has linked multiple infections during pregnancy and maternal stress to schizophrenia outcome in offspring.

Given the vast number of OCs linked to schizophrenia, the question arises as to whether any insult in a genetically vulnerable individual could lead to schizophrenia outcome, or whether some underlying mechanisms link these obstetric events to each other.

Two pathways have been linked to many of the obstetric abnormalities associated with schizophrenia: (1) decreased oxygen to the fetus, termed fetal hypoxia or asphyxia, and (2) maternal immune responses to infection and other insults during pregnancy.

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