Fabian Termorshuizen

Paternal age and psychiatric disorders: findings from a Dutch population registry.

BACKGROUND We measured the association between paternal age and schizophrenia (SCZ), autism spectrum disorders (ASD), major depressive disorder (MDD), and bipolar disorder (BPD) in the Dutch population. METHODS In total, 14231 patients and 56924 matched controls were collected and analyzed for an association with paternal age by logistic regression. RESULTS ASD is significantly associated with increased paternal age: Older fathers >40 years of age have a 3.3 times increased odds of having a child with ASD compared to young fathers <20 years of age. SCZ has significant associations for fathers aged >35 years (OR=1.27, 95% Confidence Interval: 1.05 and 1.53). For MDD, both younger and older fathers have increased odds. No association was found for BPD. CONCLUSIONS The effects of paternal age as a risk factor are different for ASD and SCZ on one hand, and the affective disorders on the other hand. Different types of association might indicate different biological or psychosocial mechanisms. Late paternity (associated with predispositions to psychiatric disorders) seems the most probable explanation for the association with paternal age.

A review of studies on the effects of ultraviolet irradiation on the resistance to infections: evidence from rodent infection models and verification by experimental and observational human studies

Recent studies on the immunosuppressive effects of ultraviolet radiation (UVR) and the related resistance to infections in rodents and humans are presented. The waveband dependency of trans-to-cis isomerisation of urocanic acid in the stratum corneum and the role of DNA damage in UVR-induced erythema and immunosuppression were investigated to further elucidate the underlying mechanisms. Furthermore, human experimental studies on UVR-induced immunomodulation were performed. It appeared that the doses needed to suppress various immune parameters in humans (e.g. NK activity, contact hypersensitivity) were higher than those needed in experiments in rodents. Still, extrapolation of experimental animal data to the human situation showed that UVR may impair the resistance to different systemic infections at relevant outdoor doses. In observational human studies we aimed to substantiate the relevance of UVR for infections in humans. It was shown that sunny season was associated with a slightly retarded but clinically non-relevant antibody response to hepatitis B vaccination. Furthermore, sunny season appeared to be associated with a small decline in the number of CD4+ T-helper cells in a cohort of HIV-infected persons and a higher recurrence of herpes simplex and herpes zoster in a cohort of renal transplant recipients. However, in a study among young children a higher exposure to solar UVR was associated with a lower occurrence of upper respiratory tract symptoms. As disentangling the effects of UVR from other relevant factors is often impossible in observational studies, concise quantitative risk estimations for the human situation cannot be given at present.

A comorbid anxiety disorder does not result in an excess risk of death among patients with a depressive disorder

BACKGROUND Several studies have demonstrated increased mortality associated with depression and with anxiety. Mortality due to comorbidity of two mental disorders may be even more increased. Therefore, we investigated the mortality among patients with depression, with anxiety and with both diagnoses. METHODS By linking the longitudinal Psychiatric Case Register Middle-Netherlands, which contains all patients of psychiatric services in the Utrecht region, to the death register of Statistics Netherlands, hazard ratios of death were estimated overall and for different categories of death causes separately. RESULTS We found an increased risk of death among patients with an anxiety disorder (N=6919): HR=1.45 (95%CI: 1.25-1.69), and among patients with a depression (N=14,778): HR=1.83, (95%CI: 1.72-1.95), compared to controls (N=103,824). The hazard ratios among both disorders combined (N=4260) were similar to those with only a depression: HR=1.91, (95% CI: 1.64-2.23). Among patients with a depression, mortality across all important disease-related categories of death causes (neoplasms, cardiovascular, respiratory, and other diseases) and due to suicide was increased, without an excess mortality in case of comorbid anxiety. LIMITATIONS The presented data are restricted to broad categories of patients in specialist services. No data on behavioral or intermediate factors were available. CONCLUSIONS Although anxiety is associated with an increased risk of death, the presence of anxiety as comorbid disorder does not give an additional increase in the risk of death among patients with a depressive disorder. The increased mortality among patients with depression is not restricted to suicide and cardiovascular diseases, but associated with a broad range of death causes.

Suicide Behavior Before and After the Start with Antidepressants: A High Persistent Risk in the First Month of Treatment Among the Young

Background: A causal relationship between antidepressants (ADs) and a high risk of suicidal behavior at a young age has been suggested. We analyzed the rates of suicide attempts during treatment with AD in comparison with the rates before treatment initiation for different ages. Methods: Claims of insurance company Achmea were linked to the population registry of Statistics Netherlands. Episodes of AD use were defined for those with their first registered prescription in 2006–2011 (n = 66,196). Rates were analyzed in a Poisson model. Correlates of attempts in the first month of AD use were assessed in a logistic model. Results: Among those aged <25 years, a high rate of suicide attempts during the month before the start of ADs was found (376.3/10 000 person yrs). A non-significant increase in the first month (p = 0.212) was found and a non-significant trend to lower values was determined thereafter (p = 0.3050). Among those ≧25 years, a clear decrease to lower rates immediately after the start was observed (p < 0.025). The highest rates of suicide were found among those >40 years during the first month. Female gender was, but treatment characteristics were not, associated with early attempts at a young age. Conclusions: Among young AD users, a high pre-treatment risk of suicide attempts was present and persisted during the early phases after the start. This contrasted with the clear decrease in risk among those aged ≧25 years, suggesting lower effectiveness of ADs to prevent suicidal behavior at young ages. Caution should be exercised to infer a causal relationship or to use data on attempts to predict risk of suicide during AD use.

Seasonal influences on immunological parameters in HIV-infected homosexual men: searching for the immunomodulating effects of sunlight

In view of the capacity of ultraviolet radiation (UVR) to induce suppression of various immunological parameters and to enhance the viral replication of HIV, we investigated whether seasonal influences on immunological parameters that are relevant for HIV infection could be identified. As the sunny season is associated with high levels of ambient UVR, a decline of immunological parameters and an increase of the HIV viral load during the summer months might ensue. We analysed the immunological data of the HIV-infected homosexual men who participated in the Amsterdam Cohort Study on HIV infection and AIDS (1984-1996; n = 556). The effect of season on the individual development of various immunological parameters in time was examined by means of a random effects model for repeated measurements. Lower levels in the mean number of CD4+ T cells and the mean CD4+/CD8+ ratio were found during summer and spring, respectively (P = 0.0001/0.0001). For the CD8+ T cells, high mean values were observed both in April and September (P = 0.0001). The highest T-cell reactivity values were found during the summer (P = 0.0001). No effect of season on the viral load was established. The seasonal effect on CD4+ T cells seemed to be more pronounced at a more advanced stage of the HIV infection. It is concluded that the lower CD4+ T-cell counts during summer support the notion that solar UVR may have a suppressive effect on the cellular immunity of HIV-infected persons. However, whether this observation can be attributed to the effect of ambient UVR solely is questionable, as the other immunological parameters follow different seasonal courses and other reports suggest that both internal and environmental factors influence immunological parameters.

An incidence study of diagnosed autism-spectrum disorders among immigrants to the Netherlands

To estimate the risk of developing autism‐spectrum disorder (ASD) in children born to immigrants as compared with children of Dutch‐born parents.

Exposure to solar ultraviolet radiation and respiratory tract symptoms in 1-year-old children

F. Termorshuizen, A. Wijga, J. Gerritsen, H. J. Neijens, H. van Loveren Laboratory for Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands, Department of Chronic Disease Epidemiology, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands, Department of Paediatric Respiratory Medicine, Beatrix Children’s Hospital, University Hospital of Groningen, University of Groningen, The Netherlands, Department of Paediatrics, Sophia Kinderziekenhuis, Rotterdam, The Netherlands, and Department of Health Risk Analysis and Toxicology, University of Maastricht, The Netherlands Dr H. J. Neijens, deceased

Psychosis and suicide risk by ethnic origin and history of migration in the Netherlands.

BACKGROUND There is an increased incidence of non-affective psychotic disorders (NAPD) among first- and second-generation migrants in Europe. The purpose of this population-based study was to compare the risk of suicide in Dutch natives and immigrants with or without NAPD. METHODS Cases of NAPD (n=12 580) from three Dutch psychiatric registers were linked to the cause of death register of Statistics Netherlands and were compared to matched controls (n=244 792) from the population register, who had no such diagnosis. Hazard ratios (HRs) of suicide were estimated and adjusted for age and gender by Cox regression analysis. RESULTS The presence of NAPD was strongly associated with suicide risk in each ethnic group. However, for all ethnic minority groups the HRs were somewhat lower than among Dutch natives, for whom the HR was 23.4 (95%-CI; 18.5-29.7). A closer examination revealed that suicide risk was influenced by the history of migration. While the risk for immigrants of the first generation, diagnosed with NAPD, was significantly lower than that for native Dutch patients (HR=0.45; 95%-CI: 0.28-0.73), the risk for those of the second generation was more similar to that for the Dutch (HR=0.85; 95%-CI: 0.51-1.40) (P value of history of migration=0.005). CONCLUSION Immigrants diagnosed with NAPD of the first generation appear to be protected against suicide, whereas this protection is waning among those of the second generation. This is the first study worldwide on suicide in migrants with NAPD and the first study of suicide in patients with NAPD in the Netherlands.

Familial clustering of schizophrenia, bipolar disorder, and major depressive disorder

Purpose:To investigate familial clustering of schizophrenia, bipolar disorder, and major depressive disorder.Methods:Combining data from a psychiatric case registry and Statistics Netherlands provided information on 4,673 affected probands and 18,692 matched population controls.Results:Probands with schizophrenia had relative risks (RRs) for having a sibling with schizophrenia of 3.77 (95% confidence interval (CI): 2.60–5.46) and with bipolar disorder of 1.79 (95% CI: 0.64–4.96) as compared with a reference proband. Probands affected with bipolar disorder have an RR of 6.51 (95% CI: 2.60–16.29) for having a sibling with bipolar disorder and of 1.71 (95% CI: 0.71–4.14) for having a sibling with schizophrenia as compared with a reference proband. Probands affected with major depressive disorder also have increased risk for having a sibling with schizophrenia (RR: 2.04, 95% CI: 1.54–2.72) as compared with a reference proband, which was similar to the risk for having a sibling with major depressive disorder (RR: 1.91, 95% CI: 1.63–2.24) or bipolar disorder (RR: 2.06, 95% CI: 1.18–3.60).Conclusion:Our findings suggest, as previous studies have, that risk across schizophrenia and bipolar disorder is considerably lower (twofold) than within diagnostic entities, whereas for major depressive disorder risk is similar within and across diagnostic entities.Genet Med 2012:14(3):338–341

Exposure to solar ultraviolet radiation in young Dutch children: assessment by means of a 6-week retrospective questionnaire

We designed a 6-week retrospective questionnaire on sunlight exposure. Estimation of the short-term exposure to sunlight is important for observational human studies concerning the effects of ultraviolet radiation (UVR) on the human immune system and related resistance to infections. This questionnaire was given to the parents of 1672 1-year-old children in the Netherlands who participated in a birth cohort study. We evaluated the questionnaire and estimated the personal 6-week cumulative exposure to solar UVR. Only 910 questionnaires (54.4%) were filled out completely and consistently. This suggests that reporting data on childrens outdoor exposure, even for the recent past, is often difficult. The data from these questionnaires indicated that the crude number of reported outdoor hours was enough to obtain a relative estimate of the individual exposure to ambient UVR, but that weighting for the effect of clothing was essential for the classification of the systemic UVR dosage received. Sunny weeks in the Netherlands in 1998, as were established by independent measurements of the levels of ambient UVR, vacations abroad, and sunburn, were associated with a comparatively high mean estimated exposure. These results support the suitability of the questionnaire for classifying the participants with respect to their short-term exposure to solar UVR.