Increased risk for pulmonary embolism in patients with bipolar disorder

OBJECTIVES: The purpose of this study was to investigate the increased risk for pulmonary embolism (PE) in patients with manic-depressive psychosis/bipolar disorder (BD). Affective patients show increased mortality compared with the background population. METHODS: A register study was carried out in which somatic and psychiatric information in 25,834 BD patients and 117,815 controls was extracted from The Danish Psychiatric Central Research Register, The National Register of Patients, The Danish Central Person Register and The Danish Register of Causes of Death, with similar information about patients with schizophrenia and anxiety for comparison. RESULTS: Patients with BD had a significantly increased occurrence of PE [increased incidence rate ratio (IRR)=1.61; 95% confidence interval (CI) (1.38, 1.88)]. An association was also found in schizophrenic patients [IRR=1.78; 95% CI (1.27, 2.51)] and in anxiety patients [IRR=1.49; 95% CI (1.10, 2.02)]. CONCLUSIONS: Increased occurrence of PE in patients with BD is one of the explanations of increased mortality in the affective patient group. A similar finding in females with schizophrenia and females with anxiety suggests 'mental disorder' as the risk factor for PE. The causes for the increased occurrence of PE in BD patients (and other diagnostic groups) need further investigation.     

A follow-up study of postpartum psychoses: prognosis and risk factors for readmission.

OBJECTIVE: The aim of this study was to describe the prognosis and risk factors for the first readmission after postpartum psychosis. METHOD: Linking the Danish Medical Birth Register and the Danish Psychiatric Central Register from 1 January 1973 to 31 December 1993 revealed 1173 women diagnosed with a psychosis within 91 days of delivery. The relative risk (RR) of readmission was estimated using Cox proportional hazard regression models. RESULTS: An increased risk of readmission was found for women with a diagnosis of schizophrenia (RR = 2.4, 95% CI = 1.9-3.1) and for women with a history of previous psychiatric admission (RR = 1.8, 95% CI = 1.5-2.1) compared to first-admitted women with other functional psychoses. Unmarried women also showed an increased risk of readmission, and only preterm delivery was associated with a reduced risk of readmission. CONCLUSION: Preterm delivery predicts the best prognosis after postpartum psychosis. The majority of readmissions were related to the psychopathology of the patient and to lack of social support.     

Risk for cancer in parents of patients with schizophrenia

OBJECTIVE: This study attempted to determine whether a genetic protection against cancer might be manifest in parents of offspring with schizophrenia. METHOD: Using data from the Danish Central Population Registry, the authors identified 1,999,072 parents of offspring born after 1935. By linking this nationwide population-based parent cohort to the Danish Psychiatric Central Register, they identified 19,856 parents of offspring with schizophrenia. Follow-up for cancer in the Danish Cancer Registry began on the date of birth of the oldest child or April 1, 1969, and ended on the date of cancer diagnosis, death, or Dec. 31, 1997, yielding a total of 48,343,430 person-years at risk and 211,681 cases of cancer. The relative risk for cancer among parents with schizophrenic offspring compared to parents with no schizophrenic offspring was estimated by Poisson regression analysis and adjusted for age, period, and number of children. RESULTS: The risk for all cancer was 1.01 for fathers and 1.00 for mothers of schizophrenics. Mothers of schizophrenic patients had an increased risk of 1.20 for lung cancer and a nonsignificant risk of 1.14 for tobacco-related cancers combined. Apart from a reduced risk for leukemia in both mothers and fathers of schizophrenics, there was no difference in risk for any other cancer. DISCUSSION: This study does not confirm a previously reported reduced risk for cancer in parents of schizophrenic patients and provides no support for genetic protection against cancer in families with schizophrenia.     

Hospital Contacts With Infection and Risk of Schizophrenia: A Population-Based Cohort Study With Linkage of Danish National Registers

Infections and immune responses have been suggested to play an important role in the etiology of schizophrenia. Several studies have reported associations between maternal infections during pregnancy and the child’s risk of schizophrenia; however, infection during childhood and adolescence unrelated to maternal infection during pregnancy has not been studied to nearly the same extent and the results are far from conclusive. Data were drawn from 2 population-based registers, the Danish Psychiatric Central Register and the Danish National Hospital Register. We used a historical population-based cohort design and selected all individuals born in Denmark between 1981 and 1996 (n = 843 390). We identified all individuals with a first-time hospital contact with schizophrenia from 1991 through 2010. Out of the 3409 individuals diagnosed with schizophrenia, a total of 1549 individuals had had a hospital contact with infection before their schizophrenia diagnosis (45%). Our results indicate that individuals who have had a hospital contact with infection are more likely to develop schizophrenia (relative risk [RR] = 1.41; 95% CI: 1.32–1.51) than individuals who had not had such a hospital contact. Bacterial infection was the type of infection that was associated with the highest risk of schizophrenia (RR = 1.63; 95% CI: 1.47–1.82). Our study does not exclude that a certain type of infection may have a specific effect; yet, it does suggest that schizophrenia is associated with a wide range of infections. This association may be due to inflammatory responses affecting the brain or genetic and environmental risk factors aggregating in families.Key words: register, Denmark, cohort study, epidemiology     

Autoimmune diseases in patients with multiple sclerosis and their first-degree relatives: a nationwide cohort study in Denmark

BACKGROUND: Multiple sclerosis (MS) and other autoimmune diseases might cluster. Our aim was to estimate the relative risk (RR) of other autoimmune diseases among MS patients and their first-degree relatives in a population-based cohort study. METHODS: Using the Danish Multiple Sclerosis Register, the Danish Hospital Discharge Register, and the Danish Civil Registration System, we estimated RRs for 42 different autoimmune diseases in a population-based cohort of 12 403 MS patients and 20 798 of their first-degree relatives. Ratios of observed to expected numbers of autoimmune diseases, based on national sex-, age-, and period-specific incidence rates, served as measures of the RRs. RESULTS: Compared with the general population, MS patients were at an increased risk of developing ulcerative colitis (RR = 2.0 (95% confidence interval (CI): 1.4-2.8), n = 29) and pemphigoid (RR = 15.4 (CI: 8.7-27.1), n = 12) but at reduced risk of rheumatoid arthritis (RR = 0.5 (CI: 0.4-0.8), n = 28) and temporal arteritis (RR = 0.5 (CI: 0.3-0.97), n = 11). First-degree relatives of MS patients were at increased risks of Crohn's disease (RR = 1.4 (CI: 1.04-1.9), n = 44), ulcerative colitis (RR = 1.3 (CI: 0.99-1.7), n = 51), Addison's disease (RR = 3.4 (CI: 1.3-9.0), n = 4), and polyarteritis nodosa (RR = 3.7 (CI: 1.4-10.0), n = 4). CONCLUSION: PATIENTS: with MS and their first-degree relatives seem to be at an increased risk of acquiring certain other autoimmune diseases.     

Mental illness and admission to general hospitals: a register investigation

Admissions to psychiatric departments and general hospitals in an 8-year period were studied for the 17- to 49-year-old population in 2 Danish municipalities. Information was extracted from the National Patient Register and the Danish Psychiatric Register, registers containing information on all admissions to nonpsychiatric and psychiatric departments, respectively, in Denmark. Fourteen percent of the patients who had been admitted at least once to a general hospital (or 7.5% of the background population) had an indication of a mental disorder. They comprised one fourth of all general admissions of the population during the 8-year period. Patients who had been admitted to a general hospital had a 4 times greater risk of having been admitted to a psychiatric department than the rest of the population and the risk increased markedly with number of general admissions. A pronounced association was found between the number of admissions to general hospitals and psychiatric departments; i.e., both types of admissions clustered in some individuals. The excessive general admissions of psychiatric patients were found to be correlated to all types of psychiatric diagnoses, but was less prominent in nonorganic psychoses. The implication is that there is a very close association between somatic and psychiatric morbidity and that the mentally disturbed use a great part of the nonpsychiatric health services.     

A possible association between the genetic predisposition for dizygotic twinning and schizophrenia

BACKGROUND: A previous study demonstrated a 40% higher rate of schizophrenia in dizygotic twins than in the general population. The aim of the present study is to evaluate whether genes influencing the rate of dizygotic twinning and genes of importance for developing schizophrenia can be associated. METHOD: Through record linkage between The Danish Twin Register, The Danish Psychiatric Central Register, and The Danish Civil Registration System, the rate of schizophrenia in singleton siblings of dizygotic and monozygotic twins was compared with the rate in siblings of singletons. RESULTS: The rate of first admission to hospital for schizophrenia in siblings of dizygotic twins was 35% greater than the rate in siblings of singletons. The result was statistically significant (p = 0.04). The rate in siblings of monozygotic twins was not increased. CONCLUSION: The results are in accordance with a theory of a linkage between genes influencing the rate of dizygotic twinning and genes influencing the threshold for developing schizophrenia.     

Violence of young criminals predicts schizophrenia: a 9-year register-based followup of 15- to 19-year-old criminals

Violent and aggressive behavior in preschizophrenia adolescents has been described in several studies. Our aim was to investigate the extent to which violent conviction in late adolescence predicted later schizophrenia in a cohort of young criminals. We performed a 9-year register-based followup of a complete national cohort of young convicted criminals. A total of 780, 15- to 19-year-old subjects identified in 1992 were followed up in 2001 with register linkage of the Danish Psychiatric Central Register, the Danish National Criminal Register, and the Danish National Cause of Death Register. Analyses with Cox regression were performed to identify predictors of later schizophrenia. We found at followup that 3.3 percent of the cohort had been diagnosed with schizophrenia and 4.5 percent with any psychosis. Conviction of violence in late adolescence was significantly associated (odds ratio = 4.59 [95% confidence interval (1.54; 13.74)]) with future diagnosis of schizophrenia. Violent behavior can thus be seen as part of the preschizophrenia phase of young criminals.     

Association Between Prepartum Maternal Iron Deficiency and Offspring Risk of Schizophrenia: Population-Based Cohort Study With Linkage of Danish National Registers

Recent findings suggest that maternal iron deficiency may increase the risk of schizophrenia-spectrum disorder in offspring. We initiated this study to determine whether maternal prepartum anemia influences offspring risk of schizophrenia. We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Psychiatric Central Register, and the Danish National Hospital Register. In a cohort of 1 115 752 Danish singleton births from 1978 to 1998, cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Cohort members were followed from their 10th birthday until onset of schizophrenia, death, or December 31, 2008, whichever came first. Adjusted for relevant confounders, cohort members whose mothers had received a diagnosis of anemia during pregnancy had a 1.60-fold (95% confidence interval = 1.16–2.15) increased risk of schizophrenia. Although the underlying mechanisms are unknown and independent replication is needed, our findings suggest that maternal iron deficiency increases offspring risk of schizophrenia.     

Confirming unexpressed genotypes for schizophrenia. Risks in the offspring of Fischer's Danish identical and fraternal discordant twins

Margit Fischer reported in 1971 that the risk of schizophrenia in the offspring of her Danish schizophrenic monozygotic twins and their normal cotwins was equal and not different from the risks in the children of schizophrenics in the literature. All of her identical and fraternal twins who had children and all of their offspring have been followed up through the Danish National Psychiatric Register as of 1985, some 18 years after study by Fischer. The morbid risk (age-corrected) for schizophrenia and schizophrenia-related disorders in the offspring of schizophrenic identical twins is 16.8%; it is 17.4% in their normal cotwins' offspring. The risks in the offspring of schizophrenic fraternal twins and their normal cotwins are 17.4% and 2.1%, respectively. The results suggest that discordance in identical twins may primarily be explained by the capacity of a schizophrenic genotype or diathesis to be unexpressed unless it is released by some kinds of environmental, including nonfamilial, stressors. Sporadic cases and phenocopies caused by cerebral abnormalities, diseases, or viruses would thus be deemphasized as necessary or sufficient explanatory causes for schizophrenia in our study but could account for some of the remaining discordance, infrequent phenocopies should encourage linkage researchers, but unexpression of genotypes will frustrate them.     

Excess use of coercive measures in psychiatry among migrants compared with native Danes

Norredam M, Garcia‐Lopez A, Keiding N, Krasnik A. Excess use of coercive measures in psychiatry among migrants compared with native Danes. Objective: To investigate differences in risk of compulsory admission and other coercive measures in psychiatric emergencies among refugees and immigrants compared with that among native Danes. Method: A register‐based retrospective cohort design. All refugees (n = 29 174) and immigrants (n = 33 287) who received residence permission in Denmark from 1.1.1993 to 31.12.1999 were included and matched 1 : 4 on age and sex with native Danes. Civil registration numbers were cross‐linked to the Danish Psychiatric Central Register and the Registry of Coercive Measures in Psychiatric Treatment. Results: Refugees (RR = 1.82; 95%CI: 1.45; 2.29) and immigrants (RR = 1.14; 95%CI: 0.83; 1.56) experienced higher rates of compulsory admissions than did native Danes. This was most striking for refugee men (RR = 2.00; 95%CI: 1.53; 2.61) and immigrant women (RR = 1.73; 95%CI: 1.45; 2.60). Moreover, refugees and immigrants experienced higher frequencies of other coercive measures during hospitalisation compared with native Danes. Conclusion: Coercive measures in psychiatry are more likely to be experienced by migrants than by native Danes.     

Fetal Growth and Schizophrenia: A Nested Case-Control and Case-Sibling Study

The association between low birth weight and schizophrenia has been suggested by many studies. Small for gestational age (SGA) is a measure used as a proxy for intrauterine growth restriction. We aim to examine if children who are born SGA are at increased risk of developing schizophrenia and whether an association may be explained by factors shared among siblings. We linked 3 population-based registers: the Danish National Medical Birth Register, the Danish Psychiatric Central Register, and the Danish Civil Registration register to identify all persons born between 1978 and 2000. A nested case-control study and a case-sibling study design were used. There were 4650 cases of schizophrenia. Incidence rate ratios (IRRs) were estimated using conditional logistic regression. SGA was defined as the lowest 10th birth weight percentile for a given sex and gestational age. SGA was associated with an IRR of 1.23 (95% CI: 1.11–1.37) for schizophrenia in the case-control study. An IRR of 1.28 (95% CI: 0.97–1.68) was found in the case-sibling study. There is a modest association between SGA and schizophrenia. Our results indicate that this association is due to an independent effect of factors associated with low birth weight for gestational age per se, rather than other factors shared by siblings.Key words: register, Denmark, cohort study, epidemiology     

Registered criminality and sanctioning of schizophrenia patients

Background: Patients with schizophrenia have been shown to have an increased risk of criminality, especially violent crimes. Aims: The aim of the current study was to describe the pattern of crimes committed by Danish patients with schizophrenia and examine the sanctions given for crimes in relation to the different periods in the patients’ lives: not yet known to the psychiatric hospital system, known to the system but not yet diagnosed with schizophrenia, and after being diagnosed with schizophrenia. Methods: Information from the Danish Psychiatric Central Research Register was correlated with data from the Danish National Crime Register. Results: One of the more prominent findings was that 16% of patients diagnosed with schizophrenia receive a prison sentence or a suspended prison sentence, despite the fact that Denmark is a co-signatory of the European Prison Rules and should treat, rather than imprison, individuals with schizophrenia. Conclusion: The findings suggest that greater alertness is needed in the judicial system for individuals diagnosed with schizophrenia.     

Cognitive function in childhood and early adulthood and hospital admission for schizophrenia and bipolar disorders in Danish men born in 1953

OBJECTIVE: This study examines the influence of cognitive function and change in cognitive function during adolescence on schizophrenia and bipolar disorders in adulthood and explores possible mechanisms for any associations. METHOD: A cohort of 6923 men born in Copenhagen, Denmark in 1953, who had completed assessments of cognitive performance (measured by a total test score that combines verbal, arithmetic and spatial functions) at ages 12 and 18, were followed from 1972 until 2002. Psychiatric outcomes (hospital admissions for schizophrenia and bipolar disorders) were obtained from the Danish Psychiatric Register. RESULTS: During the follow-up period 133 of the men had a discharge diagnosis of schizophrenia or schizophrenia spectrum disorder. Cognitive function measured at both ages 12 and 18 years was inversely associated with these disorders (unadjusted hazard ratio (HR) per SD of cognitive function at age 12: 0.87 (95% CI: 0.75,1.05) and at age 18: 0.72 (95% CI: 0.60,0.86)). Adjustment for birth weight, social circumstances during childhood, indicators of social integration and educational attainment at age 18 years changed these associations only slightly. When cognitive function measured at ages 12 and 18 were entered in the same model only the latter was inversely associated with risk of schizophrenia or spectrum disorder. Decline in cognitive function between ages 12 and 18 was associated with an increased risk of schizophrenia spectrum disorder (HR: 1.32 (95% CI: 1.01,1.75)). Cognitive function at both ages also showed an inverse association with bipolar disorders, though the association was imprecisely estimated due to small numbers (N=16). CONCLUSIONS: Low cognitive function at ages 12 and 18 years and cognitive decline between these two ages were associated with increased risk of schizophrenic disorders. This suggests that reduction in cognitive function during childhood may be an early symptom of these outcomes.     

Association between Attention-Deficit Hyperactivity Disorder in childhood and schizophrenia later in adulthood

PurposeTo estimate the risk of schizophrenia in adulthood among children and adolescents with ADHD compared to the background population.Subjects/materials and methodsTwo hundred and eight youths with ADHD (183 boys; 25 girls) were followed prospectively. Diagnoses of schizophrenia were obtained from The Danish Psychiatric Central Register. The relative risk (RR) of schizophrenia for cases with ADHD, compared to the normal population, was calculated as risk ratios. Hazard ratios (HR's) by Cox regression were calculated in the predictor analyses.ResultsMean age for ADHD cases at follow-up was 31.1 years. Schizophrenia diagnoses were given to 3.8% of these cases. Compared to the general population, RR of schizophrenia in cases with ADHD was 4.3 (95% CI 1.9–8.57).Discussion and conclusionThis prospective follow-up study found children with ADHD to be at higher risk of later schizophrenia than controls. If replicated, these results warrant increased focus on the possible emergence symptoms of schizophrenia or schizophreniform psychosis during clinical follow-up of patients with ADHD.     

Somatic Diseases and Conditions Before the First Diagnosis of Schizophrenia: A Nationwide Population-based Cohort Study in More Than 900 000 Individuals

Objective: Schizophrenia is associated with excess physical comorbidity. Yet, to our knowledge, large studies are lacking on the associations with somatic diseases before the onset of schizophrenia. The authors conducted a nationwide study of the full spectrum of treated somatic diseases before the first diagnosis of schizophrenia. Method: Nationwide sample of the Danish population consisting of singletons (n = 954351) born 1977–1993 and followed from birth to 2009, during which period 4371 developed schizophrenia. Somatic diagnoses at all general hospital contacts (admitted or outpatient care at a somatic hospital) from 1977 to 2009 were used as exposures. The incidence rate ratio (IRR) of schizophrenia was calculated using Poisson regression adjusted for confounders. Results: Among the 4371 persons who developed schizophrenia from 1992 to 2009, a total of 4180 (95.6%) persons had a previous somatic hospital contact. A history of any somatic hospital contact was associated with an elevated risk of schizophrenia (IRR = 2.04, 95% CI = 1.77–2.37). A wide range of somatic diseases and conditions were associated with an increased risk of schizophrenia, including epilepsy (IRR = 2.26, 95% CI = 1.93–2.62), nutritional or metabolic disorders (IRR = 1.57, 95% CI = 1.39–1.77), circulatory system diseases (IRR = 1.63, 95% CI= 1.38–1.92), and brain injury (IRR = 1.58, 95% CI = 1.45–1.72). Conclusions: A wide range of potential etiological factors could have contributed to the observed associations, including genetic or physiological overlaps between conditions, and interacting immunological, behavioral, and neurodevelopmental factors.Key words: schizophrenia, risk factors, physical illness     

The factor structure and reliability of the Illness Attitude Scales in a student and a patient sample

Background

Urban birth or upbringing increase schizophrenia risk. Though unknown, the causes of these urban-rural differences have been hypothesized to include, e.g., infections, diet, toxic exposures, social class, or an artefact due to selective migration.

Methods

We investigated the hypothesis that traffic related exposures affect schizophrenia risk and that this potential effect is responsible for the urban-rural differences. The geographical distance from place of residence to nearest major road was used as a proxy variable for traffic related exposures. We used a large population-based sample of the Danish population (1.89 million people) including information on all permanent addresses linked with geographical information on all roads and house numbers in Denmark. Schizophrenia in cohort members (10,755 people) was identified by linkage with the Danish Psychiatric Central Register.

Results

The geographical distance from place of residence to nearest major road had a significant effect. The highest risk was found in children living 500–1000 metres from nearest major road (RR = 1.30 (95% Confidence Interval: 1.17–1.44). However, when we accounted for the degree of urbanization, the geographical distance to nearest major road had no significant effect.

Conclusion

The cause(s) or exposure(s) responsible for the urban-rural differences in schizophrenia risk were closer related to the degree of urbanization than to the geographical distance to nearest major road. Traffic related exposures might thus be less likely explanations for the urban-rural differences in schizophrenia risk.     

Why has the incidence of schizophrenia in Danish psychiatric institutions decreased since 1970?

From The Danish Psychiatric Register five cohorts of all first-admitted patients to Danish psychiatric institutions from the years 1970, 1973, 1976, 1979, and 1980 have been followed, and trends in age-standardized rates of schizophrenia investigated. The first-admission rates have decreased in both sexes, significantly in males. In addition, the cumulated schizophrenia rates for the cohorts, including those of patients diagnosed as schizophrenics only at a later admission within periods of 2 and 5 years, decreased. This decrease is significant at 2 years of observation in both sexes and at 5 years in females. The decreasing first-admission rates might be explained partly by changes in diagnostic habits. The differential diagnoses of schizophrenia (paranoid states (ICD-8:297), paranoid reactive psychoses (298.3), unspecified psychoses (298.9 and 299), and borderline states (ICD-8 Danish version: 301.83] are increasingly used as first-admission diagnosis for patients later to be diagnosed as schizophrenic, possibly owing to a tendency to avoid the diagnosis of schizophrenia, when treatment of a patient is possible. A method of calculating the hospital incidence of schizophrenia approaching the real incidence better than the incidence of first-admission diagnoses is suggested.     

Obstetric factors, urbanization and psychosis

BACKGROUND: Epidemiologic evidence as early as the 1930s has suggested urbanization is linked to schizophrenia, either by place of admission, place of upbringing, or, more recently, place of birth. In the past decade, obstetric complications have been implicated in the etiology of schizophrenia. METHODS: With appropriate protections for anonymity, the files of the Danish Medical Birth Register were linked with the files of the Danish Psychiatric Case Register. The linkage produced 132 cases of schizophrenia and 69 cases of affective psychosis, who were born in 1973 or later, who entered a Danish psychiatric hospital before 1994. Controls were drawn from a 10% sample of the Medical Birth Register. Analysis was by logistic regression. RESULTS: The risk of hospitalization for schizophrenia was 4.20 times higher (95% CI=2.4-7.4) for those born in Copenhagen versus those born in rural areas of Denmark, and a linear relationship was demonstrated between urbanization of birthplace and risk. There was no difference in risk of hospitalization for affective psychosis for those born in Copenhagen versus rural areas. Obstetric complications had a moderate sized relationship to schizophrenia, but the relationship of urban birth to schizophrenia was unaffected by adjustment for obstetric complications. CONCLUSION: Urban birth is a strong risk factor for schizophrenia, not mediated by obstetric complications, which deserves further exploration.     

The effects of genetic liability for schizophrenia and maternal smoking during pregnancy on obstetric complications

The purpose of this study was to determine whether a genetic vulnerability for schizophrenia and/or health-risk behaviors among schizophrenic pregnant women were associated with an increased incidence of obstetric complications (OCs). METHOD: A high-risk birth cohort was formed by searching the Finnish Perinatal Register for all births from 1991-2000 with arterial cord pH values below 7.20, an indication of fetal asphyxia. This database was merged with national hospital discharge registries to determine psychiatric morbidity of the mothers and the mothers' first-degree relatives. Mothers were divided into 3 groups: women diagnosed with schizophrenia/schizoaffective disorder (n=53), mothers with a first-degree relative with schizophrenia/schizoaffective disorder (n=590) and healthy controls (n=36,895). RESULT: Schizophrenic women had significantly more OCs than mothers with a first-degree schizophrenic relative and controls. These women had significantly increased rates of eclampsia, premature delivery, prenatal hospitalizations, and marginally significant increases in high blood pressure. Offspring of schizophrenic mothers had significantly decreased APGAR scores and birth weight and increased medical complications after birth. In contrast, women with a schizophrenic first-degree relative had no significant increases in OCs compared to controls. Schizophrenic mothers also smoked more than the other groups and smoking was found to mediate the relationship between maternal schizophrenic status and decreased birth weight among offspring. CONCLUSIONS: Maternal schizophrenia during pregnancy leads to an increased risk of OCs, possibly due to engagement in health-risk behaviors during pregnancy, such as smoking, whereas genetic susceptibility to schizophrenia, by itself, does not appear to be related to incidence of OCs.