Suicide risk in relation to socioeconomic,demographic, psychiatric,and familial factors: a national register-based study of all suicides in Denmark, 1981-1997

OBJECTIVE: Suicide risk was addressed in relation to the joint effect of factors regarding family structure, socioeconomics, demographics, mental illness, and family history of suicide and mental illness, as well as gender differences in risk factors. METHOD: Data were drawn from four national Danish longitudinal registers. Subjects were all 21,169 persons who committed suicide in 1981-1997 and 423,128 live comparison subjects matched for age, gender, and calendar time of suicide by using a nested case-control design. The effect of risk factors was estimated through conditional logistic regression. The interaction of gender with the risk factors was examined by using the log likelihood ratio test. The population attributable risk was calculated. RESULTS: Of the risk factors examined in the study, a history of hospitalization for psychiatric disorder was associated with the highest odds ratio and the highest attributable risk for suicide. Cohabiting or single marital status, unemployment, low income, retirement, disability, sickness-related absence from work, and a family history of suicide and/or psychiatric disorders were also significant risk factors for suicide. Moreover, these factors had different effects in male and female subjects. A psychiatric disorder was more likely to increase suicide risk in female than in male subjects. Being single was associated with higher suicide risk in male subjects, and having a young child with lower suicide risk in female subjects. Unemployment and low income had stronger effects on suicide in male subjects. Living in an urban area was associated with higher suicide risk in female subjects and a lower risk in male subjects. A family history of suicide raised suicide risk slightly more in female than in male subjects. CONCLUSIONS: Suicide risk is strongly associated with mental illness, unemployment, low income, marital status, and family history of suicide. The effect of most risk factors differs significantly by gender.     

Tweaking agonist efficacy at N-methyl-D-aspartate receptors by site-directed mutagenesis

The structural basis for partial agonism at N-methyl-D-aspartate (NMDA) receptors is currently unresolved. We have characterized several partial agonists at the NR1/NR2B receptor and investigated the mechanisms underlying their reduced efficacy by introducing mutations in the glutamate binding site. Key residues were selected for mutation based on ligand-protein docking studies using a homology model of NR2B-S1S2 built from the X-ray structure of NR1-S1S2 in complex with glycine. Wild-type and mutant forms of NR2B were coexpressed with NR1 in Xenopus laevis oocytes and characterized by two-electrode voltage-clamp electrophysiology. By combining mutagenesis of residues His486 or Val686 with activation by differently substituted partial agonists, we introduce varying degrees of steric clash between the ligand and the two binding domains S1 and S2. In cases where ligand-protein docking predicts increased steric clashes between agonists and the residues forming the S1-S2 interface, the agonists clearly show decreased relative efficacy. Furthermore, we demonstrate that the mutation S690A affects both potency and efficacy in an agonist-specific manner. The results indicate that essential residues in the ligand binding pocket of NR2B may adopt different conformations depending on the agonist bound. Together, these data indicate that agonist efficacy at the NR2B subunit can be controlled by the extent of steric clashes between the agonist and the ligand binding domains and by ligand-dependent arrangements of residues within the binding pocket.     

Umbilical cord mercury concentration as biomarker of prenatal exposure to methylmercury

Biomarkers are often applied to assess prenatal exposure to methylmercury in research and surveillance. In a prospective study in the Faroe Islands, the main exposure biomarkers were the mercury concentrations in cord blood and maternal hair obtained at parturition. We have now supplemented these exposure biomarkers with mercury analyses of umbilical cord tissue from 447 births. In particular, when expressed in relation to the dry weight of the tissue, the cord mercury concentration correlated very well with that in cord blood. Structural equation model analysis showed that these two biomarkers have average total imprecision of about 30%, which is much higher than the laboratory error. The imprecision of the dry-weight-based concentration was lower than that of the wet-weight-based parameter, and it was intermediate between those of the cord blood and the hair biomarkers. In agreement with this finding, regression analyses showed that the dry-weight cord mercury concentration was almost as good a predictor of methylmercury-associated neuropsychologic deficits at 7 years of age as was the cord-blood mercury concentration. Cord mercury analysis can therefore be used as a valid measure of prenatal methylmercury exposure, but appropriate adjustment for the imprecision should be considered.     

Effect of psychiatric illness and labour market status on suicide: a healthy worker effect?

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.     

Marital and labor market status in the long run in schizophrenia

BACKGROUND: Singleness and unemployment increase the risk of schizophrenia. Schizophrenia subsequently increases the risk of singleness and unemployment. OBJECTIVE: To describe long-term changes in marital status and labor market affiliation before and after the first admission with schizophrenia. DESIGN: A case-control study.Setting and PARTICIPANTS: The sample included 5341 patients with a diagnosis of schizophrenia at the first admission to a psychiatric facility between 1970 and 1999, and 53 410 matched control subjects. A person admitted in 1999 was followed up in the registers from 1980 to 1997 (ie, from 19 to 2 years before admission). Individuals admitted in 1970 could be followed up from 10 years until 27 years after admission. MAIN OUTCOME MEASURES: Annual socioeconomic indicators. RESULTS: Individuals who were later hospitalized were more frequently living alone, unemployed, receiving social benefits, or otherwise outside the labor market when compared with controls, as early as 19 years before their first admission. For individuals with schizophrenia, the odds ratios of being unmarried or not being fully employed were significantly increased even 25 years after admission. This pattern was especially pronounced for men and for individuals who had more admissions. The ratios increased until admission, with a steeper increase in the years before admission. After admission, the odds declined to the level shown before admission and then stabilized. CONCLUSIONS: Schizophrenia hinders social achievement long before the first admission. The first hospital episode is followed by a period during which social status does not deteriorate further except for the transition into disability pension.     

The prevalence of allergic diseases in an unselected group of 6-year-old children. The DARC birth cohort study

This study determines the prevalence of atopic dermatitis, asthma, rhinoconjunctivitis, food hypersensitivity and urticaria and the frequency of sensitization in children with and without clinical allergic disease. In an ongoing prospective non-interventional birth cohort study of 562 unselected children, 404 children were subjected to interview, clinical examination, lung function measurements and allergy testing at 6 yr of age. Sensitization measured by skin prick test (SPT) and specific immunoglobulin E (S-IgE) was determined for 24 different allergens. The 1-yr period prevalence of atopic dermatitis, asthma and rhinoconjunctivitis was 14.4%, 6.2% and 13.6%. 25.7% of the children suffered from at least one of the three diseases. The frequency of sensitization in children with no disease (controls), any allergic disease, atopic dermatitis, asthma and rhinoconjunctivitis was 17%, 45%, 47%, 56% and 55% (defined as SPT ≥3 mm and/or S-IgE ≥0.35 kU/l for at least one allergen). Symptoms were linked to sensitization for 44% in the asthma group and 42% in the rhinoconjunctivitis group, whereas sensitization could not be linked to worsening of the eczema in any cases of atopic dermatitis. Overlap between the three diseases was significantly more frequent in sensitized children than in non-sensitized (19/46 = 41% vs. 9/58 = 16%, p = 0.004). The prevalence of food hypersensitivity and urticaria was 1.2% and 5.4% respectively. In unselected 6 yr old children, approximately half of the children with atopic dermatitis, asthma or rhinoconjunctivitis are IgE-sensitized. Sensitization tends to link these diseases to each other.