The role of genetic liability in the association of urbanicity at birth and during upbringing with schizophrenia in Denmark.

BACKGROUND: Studies have indicated that the association of urbanicity at birth and during upbringing with schizophrenia may be driven by familial factors such as genetic liability. We used a population-based nested case-control study to assess whether polygenic risk score (PRS) for schizophrenia was associated with urbanicity at birth and at age 15, and to assess whether PRS and parental history of mental disorder together explained the association between urbanicity and schizophrenia. METHODS: Data were drawn from Danish population registries. Cases born since 1981 and diagnosed with schizophrenia between 1994 and 2009 were matched to controls with the same sex and birthdate (1549 pairs). Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of a separate, large meta-analysis. RESULTS: Those with higher PRS were more likely reside in the capital compared with rural areas at age 15 [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01-1.40], but not at birth (OR 1.09, 95% CI 0.95-1.26). Adjustment for PRS produced almost no change in relative risks of schizophrenia associated with urbanicity at birth, but slightly attenuated those for urban residence at age 15. Additional adjustment for parental history led to slight attenuation of relative risks for urbanicity at birth [incidence rate ratio (IRR) for birth in capital = 1.54, 95% CI 1.18-2.02; overall p = 0.016] and further attenuation of relative risks for urbanicity at age 15 (IRR for residence in capital = 1.32, 95% CI 0.97-1.78; overall p = 0.148). CONCLUSIONS: While results regarding urbanicity during upbringing were somewhat equivocal, genetic liability as measured here does not appear to explain the association between urbanicity at birth and schizophrenia.

A population-based study of the risk of schizophrenia and bipolar disorder associated with parent-child separation during development.

BACKGROUND: There is growing interest in the role of childhood adversities, including parental death and separation, in the etiology of psychotic disorders. However, few studies have used prospectively collected data to specifically investigate parental separation across development, or assessed the importance of duration of separation, and family characteristics. METHOD: We measured three types of separation not due to death: maternal, paternal, and from both parents, across the ages of 1-15 years among a cohort of 985 058 individuals born in Denmark 1971-1991 and followed to 2011. Associations with narrowly and broadly defined schizophrenia and bipolar disorder in the psychiatric register were assessed in terms of separation occurrence, age of separation, and number of years separated. Interactions with parental history of mental disorder were assessed. RESULTS: Each type of separation was associated with all three outcomes, adjusting for age, sex, birth period, calendar year, family history of mental disorder, urbanicity at birth and parental age. Number of years of paternal separation was positively associated with both schizophrenia and bipolar disorder. Associations between separation from both parents and schizophrenia were stronger when separation occurred at later ages, while those with bipolar disorder remained stable across development. The first occurrence of paternal separation appeared to increase risk more when it occurred earlier in childhood. Associations differed according to parental history of mental disorder, although in no situation was separation protective. CONCLUSIONS: Effects of parental separation may differ by type, developmental timing and family characteristics. These findings highlight the importance of considering such factors in studies of childhood adversity.

The epidemiology of common mental disorders from age 20 to 50: results from the prospective Zurich cohort Study.

BACKGROUND: There are only a small number of prospective studies that have systematically evaluated standardised diagnostic criteria for mental disorder for more than a decade. The aim of this study is to present the approximated overall and sex-specific cumulative incidence of mental disorder in the Zurich cohort study, a prospective cohort study of 18-19 years olds from the canton of Zurich, Switzerland, who were followed through age 50. METHOD: A stratified sample of 591 participants were interviewed with the Structured Psychopathological Interview and Rating of the Social Consequences of Psychological Disturbances for Epidemiology, a semi-structured interview that uses a bottom-up approach to assess the past-year presence of 15 psychiatric syndromes. Seven interview waves took place between 1979 and 2008. Approximated cumulative incidence was estimated using Kaplan-Meier methods. RESULTS: Rates of mental disorder were considerably higher than those generally reported in cross-sectional surveys. We found rates ranging from 32.5% for major depressive disorder to 1.2% for Bipolar I disorder. The cumulative probability of experiencing any of the mental disorders assessed by age 50 was 73.9%, the highest reported to date. We also found that rates differed by sex for most disorders, with females generally reporting higher rates of mood, anxiety and phobic disorder, and males reporting higher rates of substance- and alcohol-related disorders. CONCLUSIONS: These findings confirm those of other long-term prospective studies that indicate the nearly universal nature of disturbances of emotion and behaviour across the life span. Greater community awareness of the normative nature of these experiences is warranted. An important area of future research is study long-term course and stability to determine who among those with such disturbances suffer from chronic disabling mental disorders. Such longitudinal studies may aid in directing services and intervention efforts where they are most needed.