Linda Kærlev

Parental occupational exposure to endocrine disrupting chemicals and male genital malformations: A study in the danish national birth cohort study

BackgroundSex hormones closely regulate development of the male genital organs during fetal life. The hypothesis that xenobiotics may disrupt endogenous hormonal signalling has received considerable scientific attention, but human evidence is scarce.ObjectivesWe analyse occurrence of hypospadias and cryptorchidism according to maternal and paternal occupational exposure to possible endocrine disrupting chemicals.MethodsWe conducted a follow-up study of 45,341 male singleton deliveries in the Danish National Birth Cohort during 1997-2009. Information on work during pregnancy was obtained by telephone interviews around gestational week 16. Parents job titles were classified according to DISCO-88. A job exposure matrix for endocrine disrupting chemicals (EDCs) was implemented to assess occupational exposures. The Medical Birth and National Hospital Register provided data on congenital anomalies diagnosed at birth or during follow-up, which ended in 2009. Crude and adjusted hazard ratios (HR) were obtained from Cox regression models.ResultsAmong all pregnancies, 6.3% were classified as possibly or probably exposed to EDCs. The most prevalent occupations conferring possible exposure were cleaners, laboratory technicians, hairdressers and agricultural workers (58% of all potentially exposed). The final cumulative incidence of cryptorchidism in boys was 2.2% (1002 cases), and of hypospadias 0.6% (262 cases). The occurrence of hypospadias increased when mothers were probably [HRa = 1.8 (95% CI 1.0-2.6)] or possibly exposed to one or more EDCs [HRa = 2.6 (95% CI 1.8-3.4). Possible paternal exposure to heavy metals increased the risk of hypospadias [HRa 2.2 (95% CI: 1.0-3.4)] and cryptorchidism [HRa 1.9 (95% CI: 1.1-2.7)]. None of the exposure groups reached statistical significance.ConclusionThe study provides some but limited evidence that occupational exposure to possible endocrine disrupting chemicals during pregnancy increases the risk of hypospadias.

Depression, the Val66Met polymorphism, age, and gender influence the serum BDNF level

Brain-derived neurotrophic factor (BDNF) has been suggested as a candidate gene for depression and numerous studies have investigated the possible association between genetic variants within BDNF and depression. Clinical studies have investigated the serum BDNF levels in individuals with depression. However, few studies have combined genetic association studies with serum BDNF measurements. The purpose of the present study was therefore to perform an investigation of BDNF using 162 individuals with depression and 289 healthy individuals. All individuals returned a completed questionnaire and participated in a semi-structured diagnostic interview. The major contribution of the present study is the integration of clinical assessment of cases and control individuals, simultaneous analyses of several genetic variants, serum BDNF measurements, and information on socio-demographic variables, lifestyle, and health indicators in a statistical model. In the present study the serum BDNF levels were increased in the depressive subjects compared to control individuals. Additionally, six SNPs were successfully analyzed, but did not associate with depression. Multiple linear regression models were applied and age, depression, gender, the Val66Met polymorphism, and the interaction between Val66Met and gender were identified as significant determinants of the serum BDNF level. In conclusion, our data demonstrate that other factors than a diagnosis of depression influence the serum BDNF level and the importance of these factors should be emphasized comparing different studies.

Work-unit measures of organisational justice and risk of depression—a 2-year cohort study

Objectives The aim of this study is to analyse if low justice at work, analysed as aggregated workplace means, increases the risk of depression. Methods A total of 4237 non-depressed Danish public employees within 378 different work units were enrolled in 2007. Mean levels of procedural and relational justice were computed for each work unit to obtain exposure measures that were robust to reporting bias related to depression. Two years later in 2009, 3047 (72%) participated at follow-up. Those reporting high levels of depressive, burn-out or stress symptoms were assigned to a psychiatric diagnostic interview. In the interview 58 cases of new onset depression were identified. Depression ORs by work unit level of procedural and relational justice were estimated by multivariable logistic regression accounting for established risk factors for depression. Results Working in a work unit with low procedural justice (adjusted ORs of 2.50, 95% CI 1.06 to 5.88) and low relational justice (3.14, 95% CI 1.37 to 7.19) predicted onset of depression. Conclusions Our results indicate that a work environment characterised by low levels of justice is a risk factor for depression.

Salivary cortisol and sleep problems among civil servants

OBJECTIVEnThe present study used information from a field study conducted among 4489 civil servants (70% women) in Denmark in 2007. The purpose was to examine the association between sleep problems and salivary cortisol by using a cross-sectional design with repeated measures in a subsample three-month later.nnnMETHODSnSleep problems during the past night and the past 4 weeks were assessed by a self-administered questionnaire on overall sleep quality, disturbed sleep, sleep length and awakening problems. Saliva samples were collected in a single day, using cotton tubes, 30 min after awakening and again at 2000 h. A subsample of 387 participants collected saliva samples three-month later at awakening, +20 min and +40 min after awakening and at 2000 h. We adjusted for confounders related to sampling time, life style and personal characteristics, socioeconomic status and work aspects.nnnRESULTSnSleep problems during the past four weeks were associated with low morning and evening saliva cortisol concentrations: [-3.1% per score of disturbed sleep (p=.009); and -4.7% per score of awakening problems (p<.001)]. Whereas sleep problems were not related with slope (the morning to evening change in cortisol levels). Awakening problems predicted lower cortisol (-7.51% per score; p=.003) three-month later. Cortisol awakening response (CAR) and slope three-month later were significantly associated with disturbed sleep (-7.84% and -8.24%) and awakening problems (-6.93). Area under the curve (AUC(morning)) increased with disturbed sleep (3.77%).nnnCONCLUSIONnSurprisingly, low morning cortisol was associated with increased sleep problems during a four-week period prior to sampling among 4066 Danish civil servants. At follow-up three-month later, those with sleep problems had a flattened cortisol profile. Those with awakening problems also had low salivary cortisol in general.

The norepinephrine transporter gene is a candidate gene for panic disorder

Panic disorder (PD) is an anxiety disorder characterized by recurrent panic attacks with a lifetime prevalence of 4.7%. Genetic factors are known to contribute to the development of the disorder. Several lines of evidence point towards a major role of the norepinephrine system in the pathogenesis of PD. The SLC6A2 gene is located on chromosome 16q12.2 and encodes the norepinephrine transporter (NET), responsible for the reuptake of norepinephrine into presynaptic nerve terminals. The aim of the present study was to analyze genetic variants located within the NET gene for association with PD. The case–control sample consisted of 449 patients with PD and 279 ethnically matched controls. All cases fulfilled the ICD-10 diagnostic criteria for PD. Genotyping was performed using the Sequenom platform (Sequenom, Inc, San Diego, USA). To test for allelic and haplotypic association, the PLINK software was used, and COMBASSOC was applied to test for gene-wise association. After quality control 29 single nucleotide polymorphisms (SNPs) spanning the gene-region were successfully analyzed. Seven SNPs located within the 5′ end of the gene were significantly associated with PD. Furthermore, the NET gene showed overall evidence for association with the disease (Pxa0=xa00.000035). In conclusion, the present study indicates that NET could be a susceptibility gene for PD.

A two-year follow-up study of salivary cortisol concentration and the risk of depression

Stress is a suspected cause of depression. High cortisol concentration, a biomarker of an activated stress response, has been found in depressed patients. The aim of this study was to determine if a high level of salivary cortisol is a risk factor of depression. In 2007, we enrolled 4467 public employees. Morning and evening salivary cortisol concentration were measured for each participant. Participants reporting high levels of depressive, burnout, or stress symptoms, assessed by questionnaires were assigned to a psychiatric interview. In this interview 98 participants were diagnosed with depression and subsequently excluded. Two years later in 2009, 2920 participants who had provided at least one valid saliva cortisol measurement at baseline participated at follow up. The psychiatric interviews were repeated and 62 cases of newly onset depression were diagnosed. Odds ratios of depression were estimated for every 1.0nmol/l increase in morning, evening, and daily mean cortisol concentration, as well as for the difference between morning and evening cortisol concentration. The risk of depression decreased by increasing daily mean cortisol concentration and by increasing difference between morning and evening concentrations, while morning and evening cortisol concentrations were not significantly associated with depression. The adjusted odds ratios for 1.0nmol/l increase in morning, evening, and daily mean cortisol concentration were 0.69 (95% CI: 0.45, 1.05), 0.87 (95% CI: 0.59, 1.28), and 0.53 (95% CI: 0.32, 0.90), respectively. The adjusted odds ratio for 1.0nmol/l increase in difference between morning and evening concentration were 0.64 (95% CI: 0.45, 0.90). This study did not support the hypothesis that high salivary cortisol concentration is a risk factor of depression, but indicate that low mean salivary cortisol concentration and a small difference between morning and evening cortisol concentration may be risk factors of depression.

Salivary cortisol and depression in public sector employees: cross-sectional and short term follow-up findings

INTRODUCTIONnIncreased cortisol levels have been suggested to play a role in the development of depression. An association has been shown in some studies but not consistently. The timing of an association is uncertain, and long-term follow-up studies may miss associations in narrower time windows. In the present study, we examined the association of several cortisol measures and depression in a repeated cross-sectional and short-term follow-up design. Depression was assessed by both self-reported symptoms of depression and clinical interviews.nnnMETHODnIn 2007, 10,036 public sector employees received a questionnaire along with salivary cortisol test tubes for home administration. Morning (30min after awakening) and evening (2000h) salivary samples were collected. Questionnaires and valid saliva samples were returned from 3536 employees. Approximately 3.6 months later a subsample of the participants collected three morning saliva samples (at awakening, 20min and 40min after awakening) plus an evening sample (2000h); participants with high baseline scores of self-reported depressive symptoms, burnout and perceived stress were invited to a standardized interview (SCAN) to detect clinical depression; and the symptom questionnaire was repeated for subsample participants. The study was repeated in 2009 with questionnaires and salivary test tubes (n=2408). In four cross-sectional and two short-term follow-up analyses odds ratios of depressive symptoms and of clinical depression were estimated by logistic regression for morning, evening, mean and the difference between morning and evening cortisol (slope). For the subsample, awakening response (CAR) and area under the curve (AUC) cortisol measures were calculated. We adjusted for sex, age, income, education, family history of depression, physical activity and alcohol consumption.nnnRESULTSnNone except one of the measures of salivary cortisol were associated with self-reported depressive symptoms or clinical depression, neither in the four cross-sectional analyses nor in the two short term follow-up analyses. E.g. in 2007, the adjusted odds ratios (OR) of depressive symptoms by a one unit increase in morning and evening cortisol (ln(nmol/litre saliva)) were 1.01 (95% CI: 0.88-1.17) and 1.05 (0.93-1.18), respectively. The one exception was significant at p=0.04 and was considered as due to chance.nnnCONCLUSIONnIn this large study, salivary cortisol was not associated with self-reported symptoms of depression or with clinical depression.

61. Toxoplasma gondii seropositivity is positively associated with anxiety and burnout-syndrome

Toxoplasma gondii (TOX) is a common parasite affecting approximately one-third of the human population, primarily targeting neurons and causing neuroinflammation. An increasing number of studies are providing evidence that the disease is associated with behavioural changes and psychiatric disease. The objective of this study is to examine TOX seropositivity in a large human population in relation to psychiatric symptoms. A population of 548 participants was initially included and the participants went through a semi-structured diagnostic interview (SCAN interview) followed by blood sampling. From this population, a control group ( n xa0=xa0158) with no diagnosis of psychiatric disorders was extracted as well as a group consisting of subjects showing symptoms of anxiety ( n xa0=xa0106) and burnout syndrome ( n xa0=xa051). Blood serum was examined for IgG antibodies to TOX using ELISA assays. Data were analysed using logistic regression models and show that seropositivity of TOX is positively associated with anxiety (adjusted odds ratio [OR]=2.05; 95% CI, 1.14–3.70; p xa0=xa00.016). In addition, we find an association between seropositivity and burnout syndrome (ORxa0=xa03.43; 95% CI, 1.67–7.05; p