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Loneliness and social isolation have negative health consequences and are associated with depression. Personality characteristics are important when studying persons at risk for loneliness and social isolation. The objective of this study was to clarify the association between personality factors, loneliness and social network, taking into account diagnosis of depression, partner status and gender.
Cross-sectional data of an ongoing prospective cohort study, the Netherlands Study of Depression in Older Persons (NESDO), were used.
Setting and participants:
474 participants were recruited from mental health care institutions and general practitioners in five different regions in the Netherlands.
NEO-Five Factor Inventory (NEO-FFI) personality factors and loneliness and social network were measured as well as possible confounders. Multinominal logistic regression analyses were performed to analyse the associations between NEO-FFI factors and loneliness and social network. Interaction terms were investigated for depression, partner status and gender.
Higher neuroticism and lower extraversion in women and lower agreeableness in both men and women were associated with loneliness but not with social network size irrespective of the presence of depression. In the non-depressed group only, lower openness was associated with loneliness. Interaction terms with partner status were not significant.
Personality factors are associated with loneliness especially in women. In men lower agreeableness contributes to higher loneliness. In non-depressed men and women, lower openness is associated with loneliness. Personality factors are not associated with social network size.
As depression has a recurrent course, relapse and recurrence prevention is essential.
In our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/−AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact.
Data were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model.
Mean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/−AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/−AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/−AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/−AD.
Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/−AD will become cost-effective.
Declaration of interest
C.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.
Fe is an essential nutrient for many bacteria, and Fe supplementation has been reported to affect the composition of the gut microbiota in both Fe-deficient and Fe-replete individuals outside pregnancy. This study examined whether the dose of Fe in pregnancy multivitamin supplements affects the overall composition of the gut microbiota in overweight and obese pregnant women in early pregnancy. Women participating in the SPRING study with a faecal sample obtained at 16 weeks’ gestation were included in this substudy. For each subject, the brand of multivitamin used was recorded. Faecal microbiome composition was assessed by 16S rRNA sequencing and analysed with the QIIME software suite. Dietary intake of Fe was assessed using a FFQ at 16 weeks’ gestation. Women were grouped as receiving low (<60 mg/d, n 94) or high (≥60 mg/d; n 65) Fe supplementation. The median supplementary Fe intake in the low group was 10 (interquartile range (IQR) 5–10) v. 60 (IQR 60–60) mg/d in the high group (P<0·001). Dietary Fe intake did not differ between the groups (10·0 (IQR 7·4–13·3) v. 9·8 (IQR 8·2–13·2) mg/d). Fe supplementation did not significantly affect the composition of the faecal microbiome at any taxonomic level. Network analysis showed that the gut microbiota in the low Fe supplementation group had a higher predominance of SCFA producers. Pregnancy multivitamin Fe content has a minor effect on the overall composition of the gut microbiota of overweight and obese pregnant women at 16 weeks’ gestation.
Which neighbourhood factors most consistently impact on depression and anxiety remains unclear. This study examines whether objectively obtained socioeconomic, physical and social aspects of the neighbourhood in which persons live are associated with the presence and severity of depressive and anxiety disorders.
Cross-sectional data are from the Netherlands Study of Depression and Anxiety including participants (n = 2980) with and without depressive and anxiety disorders in the past year (based on DSM-based psychiatric interviews). We also determined symptom severity of depression (Inventory of Depression Symptomatology), anxiety (Beck Anxiety Inventory) and fear (Fear Questionnaire). Neighbourhood characteristics comprised socioeconomic factors (socioeconomic status, home value, number of social security beneficiaries and percentage of immigrants), physical factors (air pollution, traffic noise and availability of green space and water) and social factors (social cohesion and safety). Multilevel regression analyses were performed with the municipality as the second level while adjusting for individual sociodemographic variables and household income.
Not urbanization grade, but rather neighbourhood socioecononomic factors (low socioeconomic status, more social security beneficiaries and more immigrants), physical factors (high levels of traffic noise) and social factors (lower social cohesion and less safety) were associated with the presence of depressive and anxiety disorders. Most of these neighbourhood characteristics were also associated with increased depressive and anxiety symptoms severity.
These findings suggest that it is not population density in the neighbourhood, but rather the quality of socioeconomic, physical and social neighbourhood characteristics that is associated with the presence and severity of affective disorders.
Estimating the risk of a complicated course of Clostridium difficile infection (CDI) might help doctors guide treatment. We aimed to validate 3 published prediction models: Hensgens (2014), Na (2015), and Welfare (2011).
The validation cohort comprised 148 patients diagnosed with CDI between May 2013 and March 2014. During this period, 70 endemic cases of CDI occurred as well as 78 cases of CDI related to an outbreak of C. difficile ribotype 027. Model calibration and discrimination were assessed for the 3 prediction rules.
A complicated course (ie, death, colectomy, or ICU admission due to CDI) was observed in 31 patients (21%), and 23 patients (16%) died within 30 days of CDI diagnosis. The performance of all 3 prediction models was poor when applied to the total validation cohort with an estimated area under the curve (AUC) of 0.68 for the Hensgens model, 0.54 for the Na model, and 0.61 for the Welfare model. For those patients diagnosed with CDI due to non-outbreak strains, the prediction model developed by Hensgens performed the best, with an AUC of 0.78.
All 3 prediction models performed poorly when using our total cohort, which included CDI cases from an outbreak as well as endemic cases. The prediction model of Hensgens performed relatively well for patients diagnosed with CDI due to non-outbreak strains, and this model may be useful in endemic settings.
Several authors claimed that expression of suicidal ideation is one of the most important predictors of completed suicide. However, the strength of the association between suicidal ideation and subsequent completed suicide has not been firmly established in different populations. Furthermore, the absolute suicide risk after expression of suicidal ideation is unknown. In this meta-analysis, we examined whether the expression of suicidal ideation predicted subsequent completed suicide in various populations, including both psychiatric and non-psychiatric populations.
A meta-analysis of cohort and case–control studies that assessed suicidal ideation as determinant for completed suicide in adults. Two independent reviewers screened 5726 articles for eligibility and extracted data of the 81 included studies. Pooled risk ratios were estimated in a random effects model stratified for different populations. Meta-regression analysis was used to determine suicide risk during the first year of follow-up.
The risk for completed suicide was clearly higher in people who had expressed suicidal ideation compared with people who had not, with substantial variation between the different populations: risk ratio ranging from 2.35 (95% confidence interval (CI) 1.43–3.87) in affective disorder populations to 8.00 (95% CI 5.46–11.7) in non-psychiatric populations. In contrast, the suicide risk after expression of suicidal ideation in the first year of follow-up was higher in psychiatric patients (risk 1.40%, 95% CI 0.74–2.64) than in non-psychiatric participants (risk 0.23%, 95% CI 0.10–0.54). Past suicide attempt-adjusted risk ratios were not pooled due to large underreporting.
Assessment of suicidal ideation is of priority in psychiatric patients. Expression of suicidal ideation in psychiatric patients should prompt secondary prevention strategies to reduce their substantial increased risk of suicide.
Loneliness is highly prevalent among older people, has serious health consequences and is an important predictor of mortality. Loneliness and depression may unfavourably interact with each other over time but data on this topic are scarce.
To determine whether loneliness is associated with excess mortality after 19 years of follow-up and whether the joint effect with depression confers further excess mortality.
Different aspects of loneliness were measured with the De Jong Gierveld scale and depression with the Centre for Epidemiologic Studies Depression Scale in a cohort of 2878 people aged 55–85 with 19 years of follow-up. Excess mortality hypotheses were tested with Kaplan–Meier and Cox proportional hazard analyses controlling for potential confounders.
At follow-up loneliness and depression were associated with excess mortality in older men and women in bivariate analysis but not in multivariate analysis. In multivariate analysis, severe depression was associated with excess mortality in men who were lonely but not in women.
Loneliness and depression are important predictors of early death in older adults. Severe depression has a strong association with excess mortality in older men who were lonely, indicating a lethal combination in this group.
Minimal efficacy differences have been found between cognitive behavioral therapy (CBT) and psychodynamic therapies for depression, but little is known about patient characteristics that might moderate differential treatment effects. We aimed to generate hypotheses regarding such potential prescriptive factors.
We conducted post-hoc model-based recursive partitioning analyses alongside a randomized clinical trial comparing the efficacy of CBT and short-term psychodynamic supportive psychotherapy (SPSP). Severely depressed patients received additional antidepressant medication. We included 233 adults seeking treatment for a major depressive episode in psychiatric outpatient clinics, who completed post-treatment assessment. Post-treatment mean Hamilton Depression Rating Scale scores constituted the main outcome measure.
While treatment differences (CBT v. SPSP) were minimal in the total sample of patients (d = 0.04), model-based recursive partitioning indicated differential treatment efficacy in certain subgroups of patients. SPSP was found more efficacious among moderately depressed patients receiving psychotherapy only who showed low baseline co-morbid anxiety levels (d = −0.40) and among severely depressed patients receiving psychotherapy and antidepressant medication who reported a duration of the depressive episode of ⩾1 year (d = −0.31), while CBT was found more efficacious for such patients reporting a duration <1 year (d = 0.83).
Our findings are observational and need validation before they can be used to guide treatment selection, but suggest that knowledge of prescriptive factors can help improve the efficacy of psychotherapy for depression. Depressive episode duration and co-morbid anxiety level should be included as stratification variables in future randomized clinical trials comparing CBT and psychodynamic therapy.
Cannabis use is associated with an earlier age at onset of psychotic illness. The aim of the present study was to examine whether this association is confounded by gender or other substance use in a large cohort of patients with a non-affective psychotic disorder.
In 785 patients with a non-affective psychotic disorder, regression analysis was used to investigate the independent effects of gender, cannabis use and other drug use on age at onset of first psychosis.
Age at onset was 1.8 years earlier in cannabis users compared to non-users, controlling for gender and other possible confounders. Use of other drugs did not have an additional effect on age at onset when cannabis use was taken into account. In 63.5% of cannabis-using patients, age at most intense cannabis use preceded the age at onset of first psychosis. In males, the mean age at onset was 1.3 years lower than in females, controlling for cannabis use and other confounders.
Cannabis use and gender are independently associated with an earlier onset of psychotic illness. Our findings also suggest that cannabis use may precipitate psychosis. More research is needed to clarify the neurobiological factors that make people vulnerable to this precipitating effect of cannabis.
The relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings.
We conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed.
Current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d −0.20 to −0.33, p<0.005). Lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005). There was no significant interaction between cannabis and status on cognitive functioning.
Lifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed.
Cannabis use is common in patients with recent-onset schizophrenia and this is associated with poor disease outcome. More insight in the cognitive-motivational processes related to cannabis use in schizophrenia may inform treatment strategies. The present study is the first known to compare implicit and explicit cannabis associations in individuals with and without psychotic disorder.
Participants consisted of 70 patients with recent-onset psychotic disorder and 61 healthy controls with various levels of cannabis use. Three Single-Category Implicit Association Tests (SC-IAT) were used to assess ‘relaxed’, ‘active’ and ‘negative’ implicit associations towards cannabis use. Explicit expectancies of cannabis use were assessed with a questionnaire using the same words as the SC-IAT.
There were no differences in implicit associations between patients and controls; however, patients scored significantly higher on explicit negative affect expectancies than controls. Both groups demonstrated strong negative implicit associations towards cannabis use. Explicit relaxed expectancies were the strongest predictors of cannabis use and craving. There was a trend for implicit active associations to predict craving.
The findings indicate that patients suffering from schizophrenia have associations towards cannabis similar to controls, but they have stronger negative explicit cannabis associations. The strong negative implicit associations towards cannabis could imply that users of cannabis engage in a behaviour they do not implicitly like. Explicit relaxing expectancies of cannabis might be an important mediator in the continuation of cannabis use in patients and controls.
To gain insight into pertussis disease dynamics, we studied age-specific long-term periodicity and seasonality of pertussis in The Netherlands. Hierarchical time-series models were used to analyse the monthly reported pertussis incidence in January 1996–June 2006 by age group. The incidence of pertussis showed a slightly increasing long-term trend with highest incidence rates seen in 1996, 1999, 2001 and 2004. For all age groups the annual peak incidence was found in August, except for the 13–18 years age group where the peak occurred in November. Monthly trends in adults showed high correlation with trends in age groups 0–4 years (0·94) and 5–12 years (0·92). We found no evidence for a relationship between annual rises in pertussis and the opening of schools. Concurrent annual fluctuations of pertussis incidence in adults and infants suggest frequent transmission within and between these age groups. Studying trends offers insight into transmission dynamics and may facilitate decisions on future vaccination strategies.
Effectiveness of marker-assisted selection (MAS) and quantitative trait locus (QTL) mapping using population-wide linkage disequilibrium (LD) between markers and QTLs depends on the extent of LD and how it declines with distance between markers and QTLs in a population. Marker–QTL LD can be predicted from LD between markers. Our previous work evaluated LD measures between multi-allelic markers as predictors of usable LD of multi-allelic markers with QTLs. Since single nucleotide polymorphisms (SNPs) are the current marker of choice for high-density genotyping and LD-mapping of QTLs, the objective of this study was to use LD between multi-allelic markers to predict LD among biallelic SNPs or between SNPs and QTLs. Observable LD between multi-allelic markers was evaluated using nine measures. These included two pooled and standardized measures of LD between pairs of alleles at two markers based on Lewontin's LD measure, two pooled measures of squared correlations between alleles, one standardized measure using Hardy–Weinberg heterozygosities, and four measures based on the chi-square statistic for testing for association between alleles at two loci. The standardized chi-square measure that best predicted usable LD between multi-allelic markers and QTLs, based on our previous work, overestimated usable SNP–SNP or SNP–QTL LD. Instead, three other measures were found to be good predictors of usable SNP–SNP or SNP–QTL LD when LD is generated by drift. Therefore, the LD measure between multi-allelic markers that is best for predicting usable LD in a population depends on the type of markers (i.e. multi-allelic or biallelic) that will eventually be used for QTL mapping or MAS.
The combination of the collecting power of an ELT with an ultra-stable high resolution spectrograph opens up the possibility to measure for the first time directly the dynamical effect of the acceleration of the Universe. CODEX will also provide unique opportunities for advance in many other branches of astrophysics. The CODEX design is based on an array of several identical spectrographs. It is highly modular and can be easily adapted to a large range of sky apertures and telescope diameters. CODEX is designed to work as a seeing limited instrument. The requirements for the telescope are moderate and clearly identified.
Effectiveness of marker-assisted selection (MAS) and quantitative trait loci (QTL) mapping using population-wide linkage disequilibrium (LD) between markers and QTL depends on the extent of LD and how it declines with distance in a population. Because marker–QTL LD cannot be observed directly, the objective of this study was to evaluate alternative measures of observable LD between multi-allelic markers as predictors of usable LD of multi-allelic markers with presumed biallelic QTL. Observable LD between marker pairs was evaluated using eight existing measures and one new measure. These consisted of two pooled and standardized measures of LD between pairs of alleles at two markers based on Lewontin's LD measure, two pooled measures of squared correlations between alleles, one standardized measure using Hardy–Weinberg heterozygosities, and four measures based on the chi-square statistic for testing for association between alleles at two loci. In simulated populations with a range of LD generated by drift and a range of marker polymorphism, marker–marker LD measured by a standardized chi-square statistic (denoted χ2′) was found to be the best predictor of useable marker–QTL LD for a group of multi-allelic markers. Estimates of the level and decline of marker–marker LD with distance obtained from χ2′ were linearly and highly correlated with usable LD of those markers with QTL across population structures and marker polymorphism. Corresponding relationships were poorer for the other marker–marker LD measures. Therefore, when LD is generated by drift, χ2′ is recommended to quantify the amount and extent of usable LD in a population for QTL mapping and MAS based on multi-allelic markers.
Children do not simply grow up; they have to be educated in order to become decent adults. This belief inspired sermons, manuals on marriage and the family, belles-lettres, and, last but not least, genre painting in seventeenth-century Holland. This article examines this belief in the necessity of education by focusing on this last genre. Attention is directed at the power of images containing idealized educational messages for parents, and not at the reality of families and child-rearing. Significantly these paintings show that the Dutch portrayal of children was less a celebration of childhood as a unique stage of life than an attempt to show adults how children could be molded and shaped through a variety of educative processes.
The effect of lactose on the urinary excretion of Mg and Ca, as an index of absorption, was studied in a double-blind, crossover study during three 1-week periods. Twenty-four healthy, lactose-tolerant, adult volunteers maintained their habitual diets with the exception that all lactose-containing dairy products in the diet were replaced by 600 g/d of three specially prepared dairy products. These products were based on either lactose-enriched cow's milk or lactose-enriched, lactase (EC 184.108.40.206)-treated cow's milk, with or without added Mg, and were given in turn during 1 week. Lactose intake was increased by 127 mmol/d (46 g/d) while taking the lactose-enriched products. While taking the Mg-enriched products, Mg intake was increased by 2.8 mmol/d (69 mg/d) which was equivalent to 17% of the habitual Mg intake. Apart from the lactose and Mg intake, nutrient intake was comparable during the three dietary periods. Urinary excretions of Mg and Ca were used as indicators for their absorption. Mg supplementation significantly increased urinary Mg excretion by 0.97 mmol/d (equivalent to an increase of 18%, P < 0.001), indicating that urinary Mg excretion is a valid indicator for intestinal Mg absorption. Hydrolysis of lactose did not affect urinary excretion of Mg and Ca, which implies that lactose intake does not affect the absorption of Mg and Ca in healthy adults.
A tsetse survey was conducted around the Lambwe Valley in South West Kenya in order to establish the extent of Glossina pallidipes distribution outside the Valley. Between October 1988 and March 1989 flies were found far outside the Lambwe Valley. A proportion of these flies was infected with three species of trypanosomes. The capture of teneral flies suggested that breeding was occurring and that viable populations of G. pallidipes therefore exist away from the core breeding areas in the valley.
The milk components lactose and casein enhance the apparent absorption of magnesium and possibly also of calcium, whereas phytate, which occurs in soya-bean products, has an inhibitory effect. This implies that soya-bean beverage v. cow's milk could lower bioavailability of Mg and Ca. This hypothesis was tested in two experiments with growing rats. Feeding soya-bean beverage v. cow's milk consistently lowered body-weight gain, enhanced bone turnover, as measured by increased plasma alkaline phosphatase (EC 220.127.116.11) activity and increased urinary hydroxyproline excretion, and decreased Mg and Ca concentrations in the femur. Because the mineral compositions of the soya-bean beverage and the cow's milk were different, the intake of Mg was higher in rats fed on soya-bean beverage, whereas that of Ca was higher in rats fed on cow's milk. Supplementation of the soya-bean beverage either with phosphorus and Ca or with P, Ca and methionine, to concentrations identical to those in milk, restored growth and bone mineralization. When using diets carefully balanced for Mg, Ca, P, sodium, potassium and methionine, soya-bean beverage v. cow's milk in the diets decreased apparent absorption and urinary excretion of Mg and Ca. Hydrolysis of lactose in milk decreased absorption and urinary excretion of Mg; it did not significantly affect Ca absorption but lowered urinary Ca excretion. The present study shows that soya-bean beverage v. milk depresses Mg and Ca bioavailability, as would be predicted on the basis of reported effects of their purified components.