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Study objective: To describe gender specific suicide rates associated with partner’s psychiatric disorder, loss of a spouse, or child by suicide or other causes, being a parent, and marital status. Design: Nested case-control study. Information on causes of death, psychiatric admission, marital status, children, and socioeconomic factors was obtained from routine registers. Setting: Denmark. Participants: 9011 people aged 25–60 years who committed suicide; 180 220 age-gender matched controls; 111 172 marital partners; 174 672 children. Main results: The suicide risk in women whose partner had been first admitted with a psychiatric disorder after 31 December two years earlier was 6.9 (95% CI 3.6 to 13.0), whereas their male counterpart experienced a risk of 3.9 (2.7 to 5.6); p value gender difference = 0.39. Men who had lost their partner by suicide or other causes of death experienced a suicide risk of 46.2 (18.3 to 116.4) and 10.1 (6.5 to 15.8), respectively; the analogous risk among women were about one third: 15.8 (6.6 to 37.4) and 3.3 (1.5 to 7.2), respectively. Child bereavement by suicide or other causes imposed an approximate twofold risk increase in their parents, whereas being a parent was protective in women. Except for widows (1.6, 1.2 to 2.0) and widowers (3.0, 2.3 to 3.9) the suicide risk associated with being separated (2.0, 1.8 to 2.3), divorced (1.8, 1.7 to 2.0), never married (1.4, 1.3 to 1.6), cohabitant (1.2, 1.1 to 1.3) was virtually the same in the two sexes. Conclusions: The suicide risk is associated with partner psychiatric illness. Conjugal bereavement is particularly indicative of suicide in men, and spousal suicide is particularly indicative of suicide. Child bereavement is associated with parental suicide, while being a parent is protective against suicide in women.

The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder. Controls were randomly sampled individuals (N=30 000). Within the sample of 86 189 individuals, a total of 57 377 individuals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot samples obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the sample. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each individual, the iPSYCH2012 sample also includes longitudinal information on health, prescribed medicine, social and socioeconomic information, and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 sample is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders.

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. 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. 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). 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.

The postpartum period is well-known risk period for the first onset of autoimmune thyroid disorders (AITDs) as well as first onset of psychiatric disorders. These two disorders are some of the most prevalent medical conditions postpartum, often misdiagnosed and disabling if left untreated. Our study was designed to explore the possible bidirectional association between AITDs and psychiatric disorders during the postpartum period. A population-based cohort study through linkage of Danish national registers, which comprised 312 779 women who gave birth to their first child during 1997-2010. We conducted Poisson regression analysis to estimate the incidence rate ratio (IRR) of psychiatric disorders among women with first-onset AITDs, the IRR of AITDs among women with first-onset psychiatric disorders as well as the overlap between these disorders using a comorbidity index. Women with first-onset AITDs postpartum were more likely to have first-onset psychiatric disorders than women who did not have postpartum AITDs (IRR = 1.88, 95% confidence interval (CI): 1.25-2.81). Women with first-onset postpartum psychiatric disorders had a higher risk of AITDs than women with no psychiatric disorders (IRR = 2.16, 95% CI: 1.45-3.20). The comorbidity index 2 years after delivery was 2.26 (95% CI: 1.61-2.90), indicating a comorbidity between first-onset AITDs and psychiatric disorders. First-onset AITDs and psychiatric disorders co-occur in the postpartum period, which has relevance to further studies on the etiologies of these disorders and why childbirth in particular triggers the onset.

The link between psychotic disorders and violent offending is well established; knowledge about risk of post-illness-onset offending across the full spectrum of psychiatric disorders is lacking. We aimed to compare rates of any offending and violent offending committed after the onset of illness, according to diagnostic group, with population controls. A 25% random sample of the Danish population (n = 521 340) was followed from their 15th birthday until offending occurred. Mental health status was considered as a time-varying exposure in a Poisson regression model used to examine the duration from service contact to the offence. Males with any psychiatric contact had an incidence rate ratio (IRR) of 2.91 [95% confidence interval (CI) 2.80-3.02] for any offending; 4.18 (95% CI 3.99-4.38) for violent offending. Associations were stronger for women (IRR 4.17, 95% CI 3.95-4.40 for any offending; 8.02, 95% CI 7.20-8.94 for violent offending). Risk was similar across diagnostic groups for any offending in males, while variation between diagnostic groups was seen for male violent and female offending, both any and violent. Risk of offending, particularly violent offending, was elevated across a range of mental disorders following first contact with mental health services. The extent of variation in strength of effect across diagnoses differed by gender.

Study objective: To describe the association between labour market status and death by suicide with focus on admission with a psychiatric disorder. Design: Nested case-control study. Data from routine registers. Setting: Entire Danish population. Participants: 9011 people aged 25–60 years who committed suicide during 1982–1997 and 180 220 matched controls. Main results: In the general population, not being fully employed is associated with a twofold to threefold increased relative risk of death by suicide, compared with being fully employed. In contrast, fully employed people who have been first admitted to a psychiatric hospital within the past year are at increased suicide risk. Patients who are unemployed, social benefits recipients, disability pensioners, or otherwise marginalised on the labour market have a suicide risk of 0.60 (95% CI: 0.46 to 0.78), 0.41 (0.23 to 0.74), 0.70 (0.45 to 1.08), and 0.86 (0.53 to 1.41), respectively. Although a similar risk decrease is found in women, men, people younger than 30 years, people older than 45 years, and in people who become unemployed, the reversed effect attenuates with time since admission, and little association is seen when a marginal structural model is applied. Conclusions: Although the results show an increased suicide mortality associated with unemployment and labour market marginalisation in the general population, the results suggest little or an inverse association between unemployment and suicide in people with psychiatric illness. The associations seen suggest the need to consider healthy worker selection effects when studying the causal pathway from unemployment and psychiatric illness to suicide.

Maternal smoking has consistently been associated with multiple adverse childhood outcomes including externalizing disorders. In contrast the association between maternal smoking during pregnancy (MSDP) and internalizing (anxiety and depressive) disorders in offspring has received less investigation. We conducted a nationwide cohort study including 957635 individuals born in Denmark between 1991 and 2007. Data on MSDP and diagnoses of depression or anxiety disorders were derived from national registers and patients were followed up from the age of 5 years to the end of 2012. Hazard rate ratios (HRRs) were estimated using stratified Cox regression models. Sibling data were used to disentangle individual- and familial-level effects of MSDP and to control for unmeasured familial confounding. At the population level, offspring exposed to MSDP were at increased risk for both severe depression [HRR 1.29, 95% confidence interval (CI) 1.22-1.36] and severe anxiety disorders (HRR 1.26, 95% CI 1.20-1.32) even when controlling for maternal and paternal traits. However, there was no association between MSDP and internalizing disorders when controlling for the mother's propensity for MSDP (depression: HRR 1.11, 95% CI 0.94-1.30; anxiety disorders: HRR 0.94, 95% CI 0.80-1.11) or comparing differentially exposed siblings (depression: HRR 1.18, 95% CI 0.75-1.89; anxiety disorders: HRR 0.87, 95% CI 0.55-1.36). The results suggest that familial background factors account for the association between MSDP and severe internalizing disorders not the specific exposure to MSDP.

Objectives: To examine the risk of affective and stress related disorders among men and women employed in human service professions. Methods: Population based case-control study using data from national registers. Cases (n = 28 971) were identified in the Danish Psychiatric Central Research Register among all hospitalised patients and outpatients aged 18–65 who received a first time ever diagnosis of affective (ICD-10, F30–39) or stress related (ICD-10, F40–48) disorder from 1 January 1995 to 31 December 1998. Each case was assigned five never admitted referents (n = 144 855) of the same gender and age, randomly drawn from a 5% sample of the Danish population obtained from Statistics Denmark’s Integrated Database for Labour Market Research. Occupation held the year before matching was classified according to the Danish version of the International Classification of Occupation. Health care, education, social work, and customer services were defined as human service professions and constituted 21% of all employed in the study. Adjusted risks (hazard ratios) relative to all other occupations were calculated for 24 human service occupations. Results: The relative risk of depression in human service professions was 1.35 (95% CI 1.24 to 1.47) for women and 1.49 (95% CI 1.29 to 1.73) for men. The risk of stress was 1.18 (95% CI 1.11 to 1.26) for women and 1.49 (95% CI 1.32 to 1.67) for men. Specific professions contributed differentially to the magnitude of risk, with education and social services displaying the highest risks. No increase in risks was found in customer service occupations. Gender was a significant modifying factor with the highest risk levels in men. Conclusions: There was a consistent association between employment in human service occupations and the risk of affective and stress related disorders. Risks were highest for men working in these typically female professions. More work is needed to distinguish work hazards from effects attributable to selection mechanisms and personality characteristics.

Genomic risk profile scores (GRPSs) have been shown to predict case–control status of schizophrenia (SCZ), albeit with varying sensitivity and specificity. The extent to which this variability in prediction accuracy is related to differences in sampling strategies is unknown. Danish population-based registers and Neonatal Biobanks were used to identify two independent incident data sets (denoted target and replication) comprising together 1861 cases with SCZ and 1706 controls. A third data set was a German prevalent sample with diagnoses assigned to 1773 SCZ cases and 2161 controls based on clinical interviews. GRPSs were calculated based on the genome-wide association results from the largest SCZ meta-analysis yet conducted. As measures of genetic risk prediction, Nagelkerke pseudo- R 2 and variance explained on the liability scale were calculated. GRPS for SCZ showed positive correlations with the number of psychiatric admissions across all P -value thresholds in both the incident and prevalent samples. In permutation-based test, Nagelkerke pseudo- R 2 values derived from samples enriched for frequently admitted cases were found to be significantly higher than for the full data sets ( P target =0.017, P replication =0.04). Oversampling of frequently admitted cases further resulted in a higher proportion of variance explained on the liability scale (improvement target = 50%; improvement replication = 162%). GRPSs are significantly correlated with chronicity of SCZ. Oversampling of cases with a high number of admissions significantly increased the amount of variance in liability explained by GRPS. This suggests that at least part of the effect of common single-nucleotide polymorphisms is on the deteriorative course of illness.