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1.  Psychiatric disorders following fetal death: a population-based cohort study 
BMJ Open  2014;4(6):e005187.
Women have increased risks of severe mental disorders after childbirth and death of a child, but it remains unclear whether this association also applies to fetal loss and, if so, to which extent. We studied the risk of any inpatient or outpatient psychiatric treatment during the time period from 12 months before to 12 months after fetal death.
Cohort study using Danish population-based registers.
A total of 1 112 831 women born in Denmark from 1960 to 1995 were included. In total, 87 687cases of fetal death (International Classification of Disease-10 codes for spontaneous abortion or stillbirth) were recorded between 1996 and 2010.
Primary and secondary outcome measures
The main outcome measures were incidence rate ratios (risk of first psychiatric inpatient or outpatient treatment).
A total of 1379 women had at least one psychiatric episode during follow-up from the year before fetal death to the year after. Within the first few months after the loss, women had an increased risk of psychiatric contact, IRR: 1.51 (95% CI 1.15 to 1.99). In comparison, no increased risk of psychiatric contact was found for the period before fetal death. The risk of experiencing a psychiatric episode was highest for women with a loss occurring after 20 weeks of gestation (12 month probability: 1.95%, 95% CI 1.50 to 2.39).
Fetal death was associated with a transient increased risk of experiencing a first-time episode of a psychiatric disorder, primarily adjustment disorders. The risk of psychiatric episodes tended to increase with increasing gestational age at the time of the loss.
PMCID: PMC4054628  PMID: 24907247
Epidemiology; Obstetrics; Psychiatry
3.  Post-Stroke Mortality, Stroke Severity, and Preadmission Antipsychotic Medicine Use – A Population-Based Cohort Study 
PLoS ONE  2014;9(1):e84103.
Background and Purpose
It has been suggested that antipsychotic medication may be neuroprotective and may reduce post-stroke mortality, but studies are few and ambiguous. We aimed to investigate the post-stroke effects of preadmission antipsychotic use.
We conducted a nationwide, population-based cohort study of 81,143 persons admitted with stroke in Denmark from 2003–2010. Using Danish health care databases, we extracted data on preadmission use of antipsychotics and confounding factors. We examined the association between current, former, and never use of antipsychotics and stroke severity, length of hospital stay, and 30-day post-stroke mortality using logistic regression analysis, survival analysis, and propensity score matching.
Current users of antipsychotics had a higher risk of severe or very severe stroke on The Scandinavian Stroke Scale than never users of antipsychotics (adjusted odds ratios, 1.43; 95% CI, 1.29–1.58). Current users were less likely to be discharged from hospital within 30 days of admission than never users (probability of non-discharge, 27.0% vs. 21.9%). Antipsychotics was associated with an increased 30-day post-stroke mortality among current users (adjusted mortality rate ratios, 1.42; 95% CI, 1.29–1.55), but not among former users (adjusted mortality rate ratios, 1.05; 95% CI, 0.98–1.14).
Preadmission use of antipsychotics was associated with a higher risk of severe stroke, a longer duration of hospital stay, and a higher post-stroke mortality, even after adjustment for known confounders. Antipsychotics play an important role in the treatment of many psychiatric conditions, but our findings do not support the hypothesis that they reduce stroke severity or post-stroke mortality.
PMCID: PMC3885530  PMID: 24416196
4.  The Risk of Schizophrenia and Child Psychiatric Disorders in Offspring of Mothers with Lung Cancer and Other Types of Cancer: A Danish Nationwide Register Study 
PLoS ONE  2013;8(11):e79031.
Maternal immune responses and brain-reactive antibodies have been proposed as possible causal mechanisms for schizophrenia and some child psychiatric disorders. According to this hypothesis maternal antibodies may cross the placenta and interact with the developing CNS of the fetus causing future neurodevelopmental disorders. Therefore, we investigated if children of mothers with cancer might be at higher risk of developing psychiatric disorders, with particular focus on small-cell lung cancer, which is known to induce production of antibodies binding to CNS elements.
Nationwide population-based registers were linked, including the Danish Psychiatric Central Register and The Danish Cancer Registry. Data were analyzed as a cohort study using survival analysis techniques. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals (CIs) were used as measures of relative risk.
In general, parental cancer was not associated with schizophrenia in the offspring (IRR, 0.98; 95% CI, 0.95-1.01). Furthermore, we found no temporal associations with maternal cancer in general; neither around the pregnancy period. However, maternal small-cell lung cancer increased the risk of early-onset schizophrenia and maternal small-cell lung cancer diagnosed within 20 years after childbirth increased the risk of schizophrenia. Parental cancer was not associated with child psychiatric disorders (IRR, 1.01; 95% CI, 0.98-1.05) except for the smoking related cancers. There was a significantly increased risk of child psychiatric disorders in offspring of both mothers (IRR, 1.35; 95% CI, 1.16-1.58) and fathers (IRR, 1.47; 95% CI, 1.30-1.66) with lung cancer of all types.
In general, parental cancer did not increase the risk of schizophrenia nor of child psychiatric disorders. However, maternal small-cell lung cancer increased the risk of schizophrenia in subgroups; and lung cancer in general increased the risk of child psychiatric disorders, which could be due to risk factors associated with parental smoking.
PMCID: PMC3815227  PMID: 24223877
5.  Patterns in mortality among people with severe mental disorders across birth cohorts: a register-based study of Denmark and Finland in 1982–2006 
BMC Public Health  2013;13:834.
Mortality among patients with mental disorders is higher than in general population. By using national longitudinal registers, we studied mortality changes and excess mortality across birth cohorts among people with severe mental disorders in Denmark and Finland.
A cohort of all patients admitted with a psychiatric disorder in 1982–2006 was followed until death or 31 December 2006. Total mortality rates were calculated for five-year birth cohorts from 1918–1922 until 1983–1987 for people with mental disorder and compared to the mortality rates among the general population.
Mortality among patients with severe mental disorders declined, but patients with mental disorders had a higher mortality than general population in all birth cohorts in both countries. We observed two exceptions to the declining mortality differences. First, the excess mortality stagnated among Finnish men born in 1963–1987, and remained five to six times higher than at ages 15–24 years in general. Second, the excess mortality stagnated for Danish and Finnish women born in 1933–1957, and remained six-fold in Denmark and Finland at ages 45–49 years and seven-fold in Denmark at ages 40–44 years compared to general population.
The mortality gap between people with severe mental disorders and the general population decreased, but there was no improvement for young Finnish men with mental disorders. The Finnish recession in the early 1990s may have adversely affected mortality of adolescent and young adult men with mental disorders. Among women born 1933–1957, the lack of improvement may reflect adverse effects of the era of extensive hospitalisation of people with mental disorders in both countries.
PMCID: PMC3850635  PMID: 24025120
Birth cohort; Mental disorder; Mortality; Psychiatric care; Register study
6.  Life Expectancy and Death by Diseases of the Circulatory System in Patients with Bipolar Disorder or Schizophrenia in the Nordic Countries 
PLoS ONE  2013;8(6):e67133.
Excess mortality from diseases and medical conditions (natural death) in persons with psychiatric disorders has been extensively reported. Even in the Nordic countries with well-developed welfare systems, register based studies find evidence of an excess mortality. In recent years, cardiac mortality and death by diseases of the circulatory system has seen a decline in all the Nordic countries, but a recent paper indicates that women and men in Denmark, Finland, and Sweden, who had been hospitalised for a psychotic disorder, had a two to three-fold increased risk of dying from a cardiovascular disease. The aim of this study was to compare the mortality by diseases of the circulatory system among patients with bipolar disorder or schizophrenia in the three Nordic countries Denmark, Sweden, and Finland. Furthermore, the aim was to examine and compare life expectancy among these patients. Cause specific Standardized Mortality Rates (SMRs) were calculated for each specific subgroup of mortality. Life expectancy was calculated using Wiesler’s method.
The SMR for bipolar disorder for diseases of the circulatory system was approximately 2 in all countries and both sexes. SMR was slightly higher for people with schizophrenia for both genders and in all countries, except for men in Denmark. Overall life expectancy was much lower among persons with bipolar disorder or schizophrenia, with life expectancy being from 11 to 20 years shorter.
Our data show that persons in the Nordic countries with schizophrenia or bipolar disorder have a substantially reduced life expectancy. An evaluation of the reasons for these increased mortality rates should be prioritized when planning healthcare in the coming years.
PMCID: PMC3691116  PMID: 23826212
7.  Excess Mortality, Causes of Death and Life Expectancy in 270,770 Patients with Recent Onset of Mental Disorders in Denmark, Finland and Sweden 
PLoS ONE  2013;8(1):e55176.
Excess mortality among patients with severe mental disorders has not previously been investigated in detail in large complete national populations.
To investigate the excess mortality in different diagnostic categories due to suicide and other external causes of death, and due to specific causes in connection with diseases and medical conditions.
In longitudinal national psychiatric case registers from Denmark, Finland, and Sweden, a cohort of 270,770 recent-onset patients, who at least once during the period 2000 to 2006 were admitted due to a psychiatric disorder, were followed until death or the end of 2006. They were followed for 912,279 person years, and 28,088 deaths were analyzed. Life expectancy and standardized cause-specific mortality rates were estimated in each diagnostic group in all three countries.
The life expectancy was generally approximately 15 years shorter for women and 20 years shorter for men, compared to the general population. Mortality due to diseases and medical conditions was increased two- to three-fold, while excess mortality from external causes ranged from three- to 77-fold. Mortality due to diseases and medical conditions was generally lowest in patients with affective disorders and highest in patients with substance abuse and personality disorders, while mortality due to suicide was highest in patients with affective disorders and personality disorders, and mortality due to other external causes was highest in patients with substance abuse.
These alarming figures call for action in order to prevent the high mortality.
PMCID: PMC3555866  PMID: 23372832
8.  Chronic Somatic Comorbidity and Excess Mortality Due to Natural Causes in Persons with Schizophrenia or Bipolar Affective Disorder 
PLoS ONE  2011;6(9):e24597.
Suicide and death by accidents in persons with schizophrenia and bipolar disorder are common, but excess mortality from natural death accounts for even more years of life lost. The impact of somatic comorbidity, however, often is not duly considered in analyses and explanations of excess mortality in patients with psychotic disorders.
This study investigates and evaluates the impact of 19 severe chronic diseases on excess mortality due to diseases and medical conditions (natural death) in individuals with psychotic disorders compared with the general population using a population-based cohort study in Denmark. Incidence/mortality rate ratios of admission/mortality were calculated using survival analysis.
Cohort members with psychotic disorders had higher incidence rates of hospital contacts for almost all of the 19 disorders than the general population. The mortality rate ratio (MRR) of natural death was 7.10 (95% CI 6.45, 7.81) for schizophrenic men, decreasing to 4.64 (95% CI 4.21, 5.10) after adjustment for the somatic disorders. The same pattern existed in women and in both genders with bipolar disorder. Highest MRRs were observed for psychotic patients without hospital admissions with the investigated somatic disorders.
Chronic somatic diseases accounted for half of the excess mortality in patients with schizophrenia or bipolar disorder. Chronic disorders investigated in this paper seem to be under-treated or under-detected among such patients.
PMCID: PMC3173467  PMID: 21935426
9.  Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study 
BMJ : British Medical Journal  2005;331(7507):23.
Objectives To investigate whether age at onset of epilepsy, type of epilepsy, family history of psychosis, or family history of epilepsy affect the risk of schizophrenia or schizophrenia-like psychosis among patients with epilepsy.
Design Comparison of population based data.
Setting Danish longitudinal registers.
Subjects The cohort comprised 2.27 million people.
Main outcome measures Epilepsy, psychosis, personal birth data.
Results We found an increased risk of schizophrenia (relative risk 2.48, 95% confidence interval 2.20 to 2.80) and schizophrenia-like psychosis (2.93, 2.69 to 3.20) in people with a history of epilepsy. The effect of epilepsy was the same in men and in women and increased with age. Family history of psychosis and a family history of epilepsy were significant risk factors for schizophrenia and schizophrenia-like psychosis, and the effect of epilepsy, both in cases and families, was greater among people with no family history of psychosis. In addition, the increased risk for schizophrenia or schizophrenia-like psychosis did not differ by type of epilepsy but increased with increasing number of admissions to hospital and, particularly, was significantly greater for people first admitted for epilepsy at later ages.
Conclusions There is a strong association between epilepsy and schizophrenia or schizophrenia-like psychosis. The two conditions may share common genetic or environmental causes.
PMCID: PMC558534  PMID: 15964859
10.  Change in suicide rates for patients with schizophrenia in Denmark, 1981-97: nested case-control study 
BMJ : British Medical Journal  2004;329(7460):261.
Objective To study the change in risk of suicide among patients with schizophrenia and related disorders.
Design Nested case-control design with linked data.
Setting 4 longitudinal Danish registers.
Participants 18 744 people aged up to 75 years who committed suicide in 1981-97 individually matched with 20 controls.
Results Over the time studied the reduction in suicide rate among patients with schizophrenia and schizophrenia spectrum disorder was similar to that seen in the general population (incidence rate ratio 1.00, 95% confidence interval 0.98 to 1.03). The reduction among patients with other psychosis in the schizophrenia spectrum was faster than the reduction seen in the general population. Among people admitted to hospital with schizophrenia the risk of suicide was highest in the first year after first admission, and the excess risk was largest in the younger age groups—that is, the risk decreased per year for every additional year of age.
Conclusion The suicide rate among patients with a diagnosis of schizophrenia and related disorders has fallen. This may be due to better psychiatric treatment, reduced access to means of suicide, or improvements in treatment after suicide attempts.
PMCID: PMC498022  PMID: 15213108

Results 1-10 (10)