Esben Agerbo

Psychiatric illness and risk factors for suicide in Denmark.

BACKGROUND Several risk factors for suicide have been identified. We assessed the relative risks and population attributable risks of suicide associated with various socioeconomic factors and with previous mental illness that necessitated hospital admission. Our aim was to assist in the choice of potential strategies for preventing suicide in the general population. METHODS We did a population-based nested case-control study based on register data. Data were collected on a random 5% sample of the Danish population aged 16-78 years during a 15-year period (1980-94) and analysed with conditional logistic regression. FINDINGS 811 cases of suicide were found and 79871 controls were chosen in this population. Unemployment, low income, being single, and a history of mental illness necessitating hospital admission were associated with increased risk of suicide. However, in the multivariate analysis, the strongest risk factor was mental illness necessitating hospital admission; risk of suicide was especially high during admission (relative risk 62.6 [95% CI 41.1-95.4]) and during the year after discharge (6.51 [5.03-8.44]). The effect of socioeconomic variables decreased after adjustment for history of mental illness. The population attributable risk associated with mental illness necessitating admission to hospital was 44.6% (43.6-45.5); the attributable risks associated with the other factors were 3.0% (1.4-6.6) for unemployment and 10.3% (6.13-16.9) for being single. INTERPRETATION Suicide prevention aimed at patients who are admitted to hospital with mental disorders and improved detection and treatment of mental disorders in the general population may be the most efficient strategy to decrease risk of suicide. Reports of high relative risk and attributable risk associated with unemployment and other socioeconomic risk factors may be confounded and overestimated owing to the lack of adjustment for the association with mental disorders.

Suicide risk in relation to family history of completed suicide and psychiatric disorders: a nested case-control study based on longitudinal registers

BACKGROUND Familial clustering of suicidal behaviour has been well documented. We aimed to assess whether family history of completed suicide and mental illness that results in admission to hospital are risk factors for suicide, and whether these factors interact. METHODS We did a nested case-control study using data from Danish longitudinal registers. We included 4262 people who had committed suicide aged 9-45 years during 1981-97 (cases), and 80238 population-based controls matched for age, sex, and date of suicide. Suicide and psychiatric history of parents and siblings and socioeconomic, demographic, and psychiatric data for every case were retrieved and merged. Data were analysed with conditional logistic regression. FINDINGS A family history of completed suicide and psychiatric illness significantly and independently increased suicide risk (odds ratio 2.58 [95% CI 1.84-3.61] and 1.31 [1.19-1.45], respectively). These effects were not accounted for by the socioeconomic status and psychiatric history of cases. A history of family psychiatric illness significantly raised suicide risk only in people without a history of psychiatric illness (1.55 [1.38-1.75]), whereas a family history of suicide increased suicide risk irrespective of psychiatric illness (2.37 [1.11-5.09] and 2.66 [1.82-3.88]) for people with and without a psychiatric history, respectively. INTERPRETATION Completed suicide and psychiatric illness in relatives are risk factors for suicide, and the effect of family suicide history is independent of the familial cluster of mental disorders. Family history of suicide should be established in the assessment of suicide risk.

Somatic Hospital Contacts, Invasive Cardiac Procedures, and Mortality From Heart Disease in Patients With Severe Mental Disorder

CONTEXT Excess mortality from heart disease is observed in patients with severe mental disorder. This excess mortality may be rooted in adverse effects of pharmacological or psychotropic treatment, lifestyle factors, or inadequate somatic care. OBJECTIVES To examine whether persons with severe mental disorder, defined as persons admitted to a psychiatric hospital with bipolar affective disorder, schizoaffective disorder, or schizophrenia, are in contact with hospitals and undergoing invasive procedures for heart disease to the same degree as the nonpsychiatric general population, and to determine whether they have higher mortality rates of heart disease. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort of 4.6 million persons born in Denmark was followed up from 1994 to 2007. Rates of mortality, somatic contacts, and invasive procedures were estimated by survival analysis. MAIN OUTCOME MEASURES Incidence rate ratios of heart disease admissions and heart disease mortality as well as probability of invasive cardiac procedures. RESULTS The incidence rate ratio of heart disease contacts in persons with severe mental disorder compared with the rate for the nonpsychiatric general population was only slightly increased, at 1.11 (95% confidence interval, 1.08-1.14). In contrast, their excess mortality rate ratio from heart disease was 2.90 (95% confidence interval, 2.71-3.10). Five years after the first contact for somatic heart disease, the risk of dying of heart disease was 8.26% for persons with severe mental disorder (aged <70 years) but only 2.86% in patients with heart disease who had never been admitted to a psychiatric hospital. The fraction undergoing invasive procedures within 5 years was reduced among patients with severe mental disorder as compared with the nonpsychiatric general population (7.04% vs 12.27%, respectively). CONCLUSIONS Individuals with severe mental disorder had only negligible excess rates of contact for heart disease. Given their excess mortality from heart disease and lower rates of invasive procedures after first contact, it would seem that the treatment for heart disease offered to these individuals in Denmark is neither sufficiently efficient nor sufficiently intensive. This undertreatment may explain part of their excess mortality.

Gestational age, birth weight, and the risk of hyperkinetic disorder

Aims: To study the association between gestational age and birth weight and the risk of clinically verified hyperkinetic disorder. Methods: Nested case-control study of 834 cases and 20 100 controls with incidence density sampling. Results: Compared with children born at term, children born with gestational ages of 34–36 completed weeks had a 70% increased risk of hyperkinetic disorder (rate ratio (RR) 1.7, 95% confidence interval (CI) 1.2 to 2.5). Children with gestational ages below 34 completed weeks had an almost threefold increased risk (RR 2.7, 95% CI 1.8 to 4.1). Children born at term with birth weights of 1500–2499 g had a 90% increased risk of hyperkinetic disorder (RR 1.9, 95% CI 1.2 to 2.9), and children with birth weights of 2500–2999 g had a 50% increased risk (RR 1.5, 95% CI 1.2 to 1.8) compared with children born at term with birth weights above 2999 g. The results were adjusted for socioeconomic status of the parents, family history of psychiatric disorders, conduct disorders, comorbidity, and maternal smoking during pregnancy. Results related to birth weight were unchanged after adjusting for differences in gestational age. Conclusions: Children born preterm, also close to term, and children born at term with low birth weights (1500–2499 g) have an increased risk of clinically verified hyperkinetic disorder. These findings have important public health perspectives because the majority of preterm babies are born close to term.

A Comprehensive Nationwide Study of the Incidence Rate and Lifetime Risk for Treated Mental Disorders

IMPORTANCE Understanding the epidemiologic profile of the life course of mental disorders is fundamental for research and planning for health care. Although previous studies have used population surveys, informative and complementary estimates can be derived from population-based registers. OBJECTIVE To derive comprehensive and precise estimates of the incidence rate of and lifetime risk for any mental disorder and a range of specific mental disorders. DESIGN, SETTING, AND PARTICIPANTS We conducted a follow-up study of all Danish residents (5.6 million persons), to whom all treatment is provided by the government health care system without charge to the patient, from January 1, 2000, through December 31, 2012 (total follow-up, 59.5 million person-years). During the study period, 320,543 persons received first lifetime treatment in a psychiatric setting for any mental disorder; 489,006 persons were censored owing to death; and 69,987 persons were censored owing to emigration. Specific categories of mental disorders investigated included organic mental disorders, substance abuse disorders, schizophrenia, mood disorders, anxiety, eating disorders, personality disorders, mental retardation, pervasive developmental disorders, and behavioral and emotional disorders. EXPOSURES Age and sex. MAIN OUTCOMES AND MEASURES Sex- and age-specific incidence rates and cumulative incidences and sex-specific lifetime risks. RESULTS During the course of life, 37.66% of females (95% CI, 37.52%-37.80%) and 32.05% of males (31.91%-32.19%) received their first treatment in a psychiatric setting for any mental disorder. The occurrence of mental disorders varied markedly between diagnostic categories and by sex and age. The sex- and age-specific incidence rates for many mental disorders had a single peak incidence rate during the second and third decades of life. Some disorders had a second peak in the sex- and age-specific incidence rate later in life. CONCLUSIONS AND RELEVANCE This nationwide study provides a first comprehensive assessment of the lifetime risks for treated mental disorders. Approximately one-third of the Danish population received treatment for mental disorders. The distinct signatures of the different mental disorders with respect to sex and age have important implications for service planning and etiologic research.

Obstetric conditions and risk of first admission with schizophrenia: A Danish national register based study

A range of complications of pregnancy, abnormal fetal growth and development, and complications of delivery have been associated with increased risk of schizophrenia. Few studies have been able to adjust for a broad range of potential confounding factors. A national population nested case-control study based on Danish longitudinal registers was conducted to investigate the risk of schizophrenia associated with exposure to a range of obstetric events. The sample included 1039 first admissions to, or contacts with Danish psychiatric services with an ICD-8 or ICD-10 diagnosis of schizophrenia and 24, 826 individually matched controls. Adjusting for the other obstetric factors, family psychiatric history, and socio-economic and demographic factors, risk of schizophrenia was associated with maternal non-attendance at antenatal appointments (Incidence Rate Ratio (IRR) 2.08, 95% CI: 1.0, 4.4), gestational age of 37 weeks or below (IRR 1.51, 95% CI: 1.0, 2.2), maternal influenza (IRR 8.2, 95% CI: 1.4, 48.8), preeclampsia (IRR 2.72, 95% CI: 1.0, 7.3), threatened premature delivery (IRR 2.39, 95% CI: 1.4, 4.1), haemorrhage during delivery (IRR 2.43, 95% CI: 1.1, 5.6), manual extraction of the baby (IRR 2.15, 95% CI: 1.1, 4.4), and maternal sepsis of childbirth and the puerperium (IRR 2.91, 95% CI: 1.1, 7.9). There was no significant interaction between the obstetric factors and either sex or family psychiatric history. The data suggest a modest association between prematurity, indicators of hypoxia, maternal infections, and maternal behaviours and risk of the later development of schizophrenia after adjusting for a number of possible confounding factors.

Smoking During Pregnancy and the Risk for Hyperkinetic Disorder in Offspring

Objective. Maternal smoking during pregnancy may increase the risk for behavioral disorders. The aim of this study was to investigate the association between smoking during pregnancy and hyperkinetic and attention-deficit/hyperactivity disorder in the offspring in a large population-based study. Methods. This study was designed as a nested case-control study. Data were obtained from Danish longitudinal registers and included 170 children with hyperkinetic disorder and 3765 population-based control subjects, who were matched by age, gender, and date of birth. Potential confounders, including newborn characteristics, socioeconomic status, and family history of psychiatric illnesses, were evaluated by conditional logistic regression analyses. Results. Women who smoked during pregnancy had a 3-fold increased risk for having offspring with hyperkinetic disorder compared with nonsmokers. Socioeconomic factors and history of mental disorder in the parents or siblings seemed to confound the result to some extent (adjusted relative risk: 1.9; 95% confidence interval: 1.3–2.8). Adjustment for parental age or exclusion of children with low birth weight (<2500 g), preterm delivery (<37 weeks completed gestation), and Apgar scores <7 at 5 minutes revealed no changes in the results. Also, excluding children with conduct disorders or comorbid disorders revealed no change in the results. Conclusions. Our results showed an increased risk for hyperkinetic disorder in children of mothers who smoked during pregnancy. This could not be explained by newborn characteristics, parental socioeconomic status, family history of psychiatric hospitalizations or contact as outpatients, conduct disorders, or comorbidity.

Suicide and occupation: the impact of socio-economic, demographic and psychiatric differences

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

Midlife suicide risk, partner’s psychiatric illness, spouse and child bereavement by suicide or other modes of death: a gender specific study

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.

A comprehensive assessment of parental age and psychiatric disorders

IMPORTANCE There has been recent interest in the findings that the offspring of older fathers have an increased risk of both de novo mutations and neuropsychiatric disorders. However, the offspring of younger parents are also at risk for some adverse mental health outcomes. OBJECTIVE To determine the association between maternal and paternal age and a comprehensive range of mental health disorders. DESIGN, SETTING, AND PARTICIPANTS A comprehensive, population-based record linkage study using the Danish Psychiatric Central Research Register from January 1, 1995, through December 31, 2011. A total of 2 894 688 persons born in Denmark from January 1, 1955, through December 31, 2006, were followed up during the study period. EXPOSURES Maternal and paternal age at the time of offsprings birth. MAIN OUTCOMES AND MEASURES We examined a broad range of International Classification of Diseases-defined mental disorders, including substance use; schizophrenia and related disorders; mood disorders; neurotic, stress-related, and somatoform disorders; eating disorders; specific personality disorders; and a range of developmental and childhood disorders. The incidence rate ratios for each mental disorder outcome were estimated by log linear Poisson regression with adjustments for the calendar period, age, sex, and age of the other parent. RESULTS The cohort was observed for 42.7 million person-years, during which 218 441 members of the cohort had their first psychiatric contact for any psychiatric disorder. Based on the overall risk of psychiatric disorders, the offspring of younger and older parents were at increased risk compared with those of parents aged 25 to 29 years. When the offspring were examined for particular disorders, the nature of the relationship changed. For example, the offspring of older fathers were at an increased risk of schizophrenia and related disorders, mental retardation, and autism spectrum disorders. In contrast, the offspring of young mothers (and to a lesser extent young fathers) were at an increased risk for substance use disorders, hyperkinetic disorders, and mental retardation. CONCLUSIONS AND RELEVANCE The offspring of younger mothers and older fathers are at risk for different mental health disorders. These differences can provide clues to the complex risk architecture underpinning the association between parental age and the mental health of offspring.