CLINICAL HANDBOOK OF SCHIZOPHRENIA

66 I. CORE SCIENCE AND BACKGROUND INFORMATIONSome theorists have proposed that there may be a subgroup of patients with schizophreniawho acquire the disorder from entirely nongenetic origins. According to thismodel, an obstetric insult could cause schizophrenia independently of genetic contributions.If this model were correct, then exposure to OCs (with a given degree of severityand during a sensitive period of gestation) would lead to expression of schizophreniawith a fair degree of reliably. The prevailing evidence suggests that this model is unlikely,because the rate of OCs in the general population is far higher than the rate of schizophrenia(approximately 1% of the population). Even if OCs during particularly criticalperiods of gestation only were considered, there would likely still be a much higher rateof schizophrenia in the population if OCs were the sole cause of the disease onset. Therefore,there currently is little support for the idea that OCs alone can produce schizophrenia.Another model, the gene–environment covariation model, posits that OCs are associatedwith the genes for the disorder, but OCs do not exert any etiological role in the disease.This model predicts an increase in the number of OCs in individuals who carrygenes associated with schizophrenia, regardless of whether they develop the disorder. Themain support for the gene–environment covariation model comes from studies that foundincreased birth complications in offspring of mothers with schizophrenia (who carry thedisease-producing genes given that they express the disorder phenotypically), but it is inconsistentwith the finding that unaffected siblings of patients with schizophrenia do notdiffer from the general population in the incidence of OCs. Siblings of patients withschizophrenia would be expected to share some of the disease-promoting genes, thereforeleading to increased risk of OCs, if the gene–environment covariation model were correct.In addition, interpretation of increases in OCs among mothers with schizophrenia iscomplicated by the elevated occurrence of health-risk behaviors during pregnancy amongthis cohort. Specifically, women with schizophrenia are less likely to receive prenatal care,more likely to be polydrug users, more likely to drink alcohol, more likely to be on psychiatricmedications, and more likely to smoke cigarettes than women without schizophrenia,all of which have been associated with increases in OCs. Moreover, discontinuationof antipsychotic medication has been associated with a worsening of symptoms,often leading to psychotic episodes in relatively asymptomatic women. The onset of apsychotic episode likely has many consequences for prenatal health, including increasedstress, poor nutrition, poor self-care, suicide attempts, attempts at premature delivery,and other risky behaviors that could lead to deleterious pregnancy and birth outcomes.Given the limitations of the available data, findings that support the gene–environmentcovariation model are difficult to interpret.Most studies support the gene–environment interaction model, which asserts thatobstetric influences depend on the presence of disease-promoting genes in the etiology ofschizophrenia. According to this model, the occurrence of an OC in a genetically vulnerableindividual would increase the likelihood of that individual developing the disorder.Support for this model comes from studies in which a history of OCs differentiated betweensiblings with and without schizophrenia, suggesting that this early insult interactedwith disease-producing genes to cause the disorder. It also is possible that genetic and obstetricrisk factors for schizophrenia occur independently of each other but additively influencerisk for disease expression (additive influence model). Both the gene–environmentinteraction model and the additive influences model predict a relative increase in the rateof OCs among individuals who develop schizophrenia; therefore, the two models are oftendifficult to separate. Specifically, it is very difficult to examine directly gene–environmentinteractions or gene–environment aggregations. To do this, it is necessary to measure theenvironmental influence, as well as the gene, or genes. This may be more feasible now,