The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.

Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10–25 (N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions.

We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01–1.11) and persistent contact (1.12, 1.03–1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03–1.21).

We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

Refugees are at an elevated risk of some mental disorders with studies highlighting the contributing role of post-migration factors. Studies of migrant groups show neighborhood social composition, such as ethnic density, to be important. This is the first longitudinal study to examine this question for refugees and uses a novel quasi-experimental design.

We followed a cohort of 44 033 refugees from being first assigned housing under the Danish dispersal policy, operating from 1986 to 1998, until 2019. This comprised, in effect, a natural experiment whereby the influence of assigned neighborhood could be determined independently of endogenous factors. We examined three aspects of neighborhood social composition: proportion of co-nationals, refugees, and first-generation migrants; and subsequent incidence of different mental disorders.

Refugees assigned to neighborhoods with fewer co-nationals (lowest v. highest quartile) were more likely to receive a subsequent diagnosis of non-affective psychosis, incident rate ratio (IRR) 1.25 (95% confidence interval (CI) 1.06–1.48), and post-traumatic stress disorder (PTSD), IRR 1.21 (95% CI I.05–1.39). A comparable but smaller effect was observed for mood disorders but none observed for stress disorders overall. Neighborhood proportion of refugees was less clearly associated with subsequent mental disorders other than non-affective psychosis, IRR 1.24 (95% CI 1.03–1.50). We found no statistically significant associations with proportion of migrants.

For refugees, living in a neighborhood with a lower proportion of co-nationals is related to subsequent increased risk of diagnosed mental disorders particularly non-affective psychosis and PTSD.

General medical conditions (GMCs) often co-occur with mental and substance use disorders (MSDs).

To explore the contribution of GMCs to the burden of disease in people with MSDs, and investigate how this varied by age.

A population-based cohort of 6 988 507 persons living in Denmark during 2000–2015 followed for up to 16 years. Danish health registers were used to identify people with MSDs and GMCs. For each MSD, years lived with disability and health loss proportion (HeLP) were estimated for comorbid MSDs and GMCs, using a multiplicative model for disability weights.

Those with any MSD lost the equivalent of 43% of healthy life (HeLP = 0.43, 95% CI 0.40–0.44) after including information on GMCs, which was an increase from 25% before including GMCs (HeLP = 0.25, 95% CI 0.23–0.27). Schizophrenia was associated with the highest burden of disease (HeLP = 0.77, 95% CI 0.68–0.85). However, within each disorder, the relative contribution of MSDs and GMCs varied. For example, in those diagnosed with schizophrenia, MSDs and GMCs accounted for 86% and 14% of the total health loss; in contrast, in those with anxiety disorders, the same proportions were 59% and 41%. In general, HeLP increased with age, and was mainly associated with increasing rates of pulmonary, musculoskeletal and circulatory diseases.

In those with mental disorders, the relative contribution of comorbid GMCs to the non-fatal burden of disease increases with age. GMCs contribute substantially to the non-fatal burden of disease in those with MSDs.

Childbirth may be a traumatic experience and vulnerability to posttraumatic stress disorder (PTSD) may increase the risk of postpartum depression (PPD). We investigated whether genetic vulnerability to PTSD as measured by polygenic score (PGS) increases the risk of PPD and whether a predisposition to PTSD in PPD cases exceeds that of major depressive disorder (MDD) outside the postpartum period.

This case-control study included participants from the iPSYCH2015, a case-cohort of all singletons born in Denmark between 1981 and 2008. Restricting to women born between 1981 and 1997 and excluding women with a first diagnosis other than depression (N = 22 613), 333 were identified with PPD. For each PPD case, 999 representing the background population and 993 with MDD outside the postpartum were matched by calendar year at birth, cohort selection, and age. PTSD PGS was calculated from summary statistics from the Psychiatric Genomics Consortium with LDpred2-auto. Odds ratios (ORs) were estimated using conditional logistic regression adjusted for parental psychiatric history and country of origin, PGS for MDD and age at first birth, and the first 10 principal components.

The PTSD PGS was significantly associated with PPD (OR 1.42, 95% CI 1.20–1.68 per standard deviation increase in PTSD PGS) compared to healthy female controls. Genetic PTSD vulnerability in PPD cases did not exceed that of matched female depression cases outside the postpartum period (OR 1.10, 95% CI 0.94–1.30 per standard deviation increase).

Genetic vulnerability to PTSD increased the risk of PPD but did not differ between PPD cases and women with depression at other times.

Many studies report an ethnic density effect whereby psychosis incidence among ethnic minority groups is higher in low co-ethnic density areas. It is unclear whether an equivalent density effect applies with other types of socioeconomic disadvantages.

We followed a population cohort of 2 million native Danes comprising all those born on 1st January 1965, or later, living in Denmark on their 15th birthday. Socioeconomic disadvantage, based on parents' circumstances at age 15 (low income, manual occupation, single parent and unemployed), was measured alongside neighbourhood prevalence of these indices.

Each indicator was associated with a higher incidence of non-affective psychosis which remained the same, or was slightly reduced, if neighbourhood levels of disadvantage were lower. For example, for individuals from a low-income background there was no difference in incidence for those living in areas where a low-income was least common [incidence rate ratio (IRR) 1.01; 95% confidence interval (CI) 0.93–1.10 v. those in the quintile where a low income was most common. Typically, differences associated with area-level disadvantage were the same whether or not cohort members had a disadvantaged background; for instance, for those from a manual occupation background, incidence was lower in the quintile where this was least v. most common (IRR 0.83; 95% CI 0.71–0.97), as it was for those from a non-manual background (IRR 0.77; 95% CI 0.67–0.87).

We found little evidence for group density effects in contrast to previous ethnic density studies. Further research is needed with equivalent investigations in other countries to see if similar patterns are observed.

In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.

Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.

Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.

These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.

Residential mobility during upbringing, and especially adolescence, is associated with multiple negative mental health outcomes. However, whether associations are confounded by unmeasured familial factors, including genetic liability, is unclear.

We used a population-based case–cohort study to assess whether polygenic risk scores (PRSs) for schizophrenia, bipolar disorder and major depression were associated with mobility from ages 10–14 years, and whether PRS and parental history of mental disorder together explained associations between mobility and each disorder.

Information on cases (n = 4207 schizophrenia, n = 1402 bipolar disorder, n = 18 215 major depression) and a random population sample (n = 17 582), born 1981–1997, was linked between Danish civil and psychiatric registries. Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of separate, large meta-analyses.

PRSs for schizophrenia and major depression were weakly associated with moving once (odds ratio 1.07, 95% CI 1.00–1.16; and odds ratio 1.10, 95% CI 1.04–1.17, respectively), but not twice or three or more times. Mobility was positively associated with each disorder, with more moves associated with greater risk. Adjustment for PRS produced slight reductions in the magnitude of associations. Adjustment for PRS and parental history of mental disorder together reduced estimates by 5–11%. In fully adjusted models mobility was associated with all three disorders; hazard ratios ranged from 1.33 (95% CI 1.08–1.62; one move and bipolar disorder) to 3.05 (95% CI 1.92–4.86; three or more moves and bipolar disorder).

Associations of mobility with schizophrenia, bipolar disorder and depression do not appear to be attributable to genetic liability as measured here. Potential familial confounding of mobility associations may be predominantly environmental in nature.

Schizophrenia (SZ) and bipolar disorder (BP) are causes of severe disability worldwide and parents’ severe mental illness (SMI) is associated with childhood adversity, and socio-emotional and cognitive problems in children. Yet, how parental BP and SZ affect educational attainment in offspring is still unclear.

We included all children (N = 684.248) born and living in Denmark between 1986 and 1996 and their parents. Our follow-up lasted from 1986 until children's graduation in 2014. The main outcome variable was their school grades following their primary education. School outcomes were divided into four categories: not graduated, low-grade point average (GPA), medium GPA and high GPA. We then performed a multiple logistic regression with medium GPA as the reference category, with the children of parents without SZ or BP as the reference group.

Children of parents with SZ faced higher odds than their peers of not graduating primary education (OR 2.6), along with low GPA (odds ratios (OR) 1.6) and lower odds for a high GPA (OR 0.7). Moreover, it was the children of mothers rather than fathers with BP who had higher odds of not graduating primary education (OR 1.6). Lastly, child placement was associated with lower grades and lower graduation rates, and outcomes for children of parents with SMI were favorable compared with other children placed in care.

For children, parental SZ is associated with lower grades and lower chances for graduating primary education. In contrast, the children of parents with BP were indistinguishable from the reference group regarding school grades. This signifies that specificity of parental severe mental illness is important in relation to educational achievement of children.

People born in densely populated areas have a higher risk of developing schizophrenia, bipolar disorder and autism.

The purpose of this study was to investigate whether urban–rural differences in place of birth influence a broad range of mental disorders.

Population-based cohort study of everyone born in Denmark between 1955 and 2006 (n = 2 894 640). Main outcome measures were incidence rate ratios for five levels of urbanisation and summary estimates contrasting birth in the capital with birth in rural areas.

For all psychiatric disorders, except intellectual disability (ICD-10 ‘mental retardation’) and behavioural and emotional disorders with onset in childhood, people born in the capital had a higher incidence than people born in rural areas.

Birth in an urban environment is associated with an increased risk for mental illness in general and for a broad range of specific psychiatric disorders. Given this new evidence that urban–rural differences in incidence are not confined to the well-studied psychotic disorders, further work is needed to identify the underlying aetiopathogenic mechanisms.

To explore the risk of suicide associated with occupation while evaluating the impact of socio-economic, demographic and psychiatric differences.

A nested case–control study with 3195 suicides and 63 900 matched controls. Information on causes of death, occupation, psychiatric admission, marital status and socio-economic factors was obtained from routine registers.

Across the 55 occupations investigated, the risk of suicide ranged from 2·73 [95% confidence interval (CI) 1·77–4·22] among doctors to 0·44 (95% CI 0·27–0·72) among architects and engineers compared with primary school teachers. With the exception of doctors and nurses, most of the excess risk of suicide associated with particular occupations is explained by the social and economic characteristics of people in those occupations. Much, but not all, of the excess risk in doctors and nurses is due to their increased use of self-poisoning, a method for which they have the knowledge to use effectively. Occupation has little association with suicide among people who suffer from a psychiatric illness, except for doctors, where the excess risk is 3·62 (p=0·007).

Most of the considerable variation in suicide risk across occupations is explained by socio-economic factors, except for doctors and nurses. Apart from in doctors, the risk of suicide has little association with occupation among people who suffer from a psychiatric illness. Restriction of access to lethal means is an important strategy in suicide prevention.

The risk for schizophrenia has been associated with a family history of this and other psychiatric disorders. The relationship between age at first contact and family history of psychiatric illness is not certain.

To estimate the risks for schizophrenia associated with a range of psychiatric diagnoses in family members and to investigate the relationship between these risks and age at first contact for schizophrenia.

A nested case–control study design was employed. Psychiatric admission data and socio-economic data were available for 7704 cases admitted between 1981 and 1998 in Denmark, 192 590 gender- and age-matched controls, and for the parents and siblings of all subjects.

Controlling for socio-economic factors, risk for schizophrenia was associated with a family history of all psychiatric disorders except substance misuse and independently with a family history of suicide. The risk for schizophrenia associated with a family history of psychiatric disorders decreased as age at first contact increased.

Risk for schizophrenia is associated with a range of psychiatric disorders in family members and these risks are not constant across the risk period.

Gender is one of the most frequently replicated predictors for suicide.

To identify risk factors for suicide among males and females and to investigate whether risk factors for suicide differ by gender.

A time-matched nested case–control design was performed using Danish longitudinal register databases to obtain 811 suicide cases and 79 871 controls. Data were analysed using conditional logistic regression.

A history of hospitalised mental illness was the most marked risk factor for suicide for both genders. Unemployment, retirement, being single and sickness absence were significant risk factors for men, whereas having a child <2 years old was significantly protective for women. The relative risks for suicide differed significantly between genders according to psychiatric admission status and being the parent of a child < 2 years. However, adjustment for these factors did not eliminate the gender difference in suicide risk.

Risk factors for suicide differed by gender and gender differences could not be explained by differential exposure to known risk factors.