CLINICAL HANDBOOK OF SCHIZOPHRENIA

7. Environmental Pre- and Perinatal Influences in Etiology 67with the recent availability of serological data from pregnancy and the identification ofcandidate genes involved in schizophrenia. Nevertheless, only a handful of candidategenes have been identified, and schizophrenia is not caused by one gene, which furthercomplicates the ease of directly testing gene–environment interactions and aggregations.For our purposes in this chapter, we refer to the gene–environment interaction model, butmany of the findings may also fit into the additive influences model.Last, it is possible that multiple models are correct and operate simultaneouslywithin the disorder. This possibility has not been explored as extensively, but it will likelygain more attention with the virtual explosion of studies investigating specific geneticvariations among patients with schizophrenia, termed polymorphisms, as well as increasingattempts to map out molecular pathways implicated in the disorder. For instance, agenetic polymorphism associated with a magnified inflammatory response has beenlinked to schizophrenia (discussed further in section on prenatal infection). In thepresence of infection, this genetic polymorphism leads to increased inflammation (gene–environment interaction), the consequences of which are discussed more extensivelybelow. Interestingly, this polymorphism also is associated with increased incidence of certainOCs, such as preterm delivery (gene–environment covariation); therefore, we can seethat a gene associated with schizophrenia could have multiple functions, some others ofwhich may serve to play a role in the causes of the disorder and others of which may beunrelated to the etiology. The relatively new opportunity to investigate directly gene–environment interactions at a molecular level will certainly shed considerable light onhow OCs operate within the disorder.WHAT TYPES OF OCs ARE ASSOCIATED WITH SCHIZOPHRENIA?OCs have been linked to the etiology of schizophrenia since the 1960s when Lane andAlbee (1966) first observed that birthweights of 52 patients with schizophrenia werelower than those of their siblings without schizophrenia. Despite the fact that the differenceswere relatively small (about 175 grams), and few of the schizophrenia patients hadbirthweights that were less than 2,500 grams (the criterion for low birthweight), thisstudy raised the possibility that events during the very early stages of life may have longlastingneurobiological effects, potentially contributing to the causes of schizophrenia.Since the 1960s dozens of articles have linked aberrant events during the pre- andperinatal periods to schizophrenia. Investigations into this area have taken many forms,such as following genetically at-risk individuals (e.g., offspring of patients with schizophreniaand unaffected siblings of patients with schizophrenia), comparing the prevalenceof OCs in patients with schizophrenia and controls (often using maternal recall), and,last, taking advantage of population databases and registries containing detailed informationabout the pre- and perinatal periods, as well as information regarding psychiatricstatuses. Given the variety of study procedures, the conflicting results from many of theinvestigations exploring the role of obstetric events in the etiology of schizophrenia arenot surprising. For this reason, studies using population registries (e.g., in Scandinavia)have been especially useful in providing detailed, prospective obstetric information, in additionto having large enough samples to detect meaningful results. Recent findings frompopulation-based studies have had the added advantage of exploring molecular pathwaysin 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 havebeen associated with schizophrenia; however, we focus on the more recent, populationbasedresults, especially those using serological data.