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Mental health smartphone apps could increase the safety and self-management of patients at risk of suicide, but it is still unclear whether it is feasible to integrate such apps into routine mental healthcare. This study reports on the feasibility of using a safety planning app (BackUp) and a self-monitoring app (mEMA) as components of the routine treatment of depressed outpatients with suicidal ideation. Clinicians were trained in working with both of the apps, and they invited their eligible patients with suicidal ideation for study participation. Patients used the apps for 3 months and discussed these with their clinician during treatment. Patients completed assessments at baseline (T 0 ), 4 weeks (T 1 ) and post-test (T 2 , 12 weeks after baseline). Both patients and clinicians also participated in telephone interviews. Feasibility was assessed in terms of usability (score > 70 on System Usability Scale, SUS), acceptability (score > 20 on Client Satisfaction Questionnaire-8, CSQ-8), and uptake (sufficient rates of component completion and app usage in treatment). The sample included 17 adult outpatients (52.9% male, age range 20-50 years) diagnosed with a depressive disorder and suicidal ideation at baseline. BackUp was rated by patients at above the cut-off scores for usability (SUS mean score at T 1 75.63 and at T 2 77.71) and acceptability (CSQ-8 mean score at T 1 23.42 and at T 2 23.50). mEMA was similarly rated (SUS mean score at T 1 75.83 and at T 2 76.25; CSQ-8 mean score at T 1 23.92 and at T 2 22.75). Telephone interviews with patients and clinicians confirmed the usability and acceptability. The uptake criteria were not met. Our findings suggest that mobile safety planning and mobile self-monitoring can be considered acceptable and usable as treatment components for depressed suicidal outpatients, but the integration of apps into routine treatment needs to be further explored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nuij, van Ballegooijen, de Beurs, de Winter, Gilissen, O’Connor, Smit, Kerkhof and Riper.)

Background: Longitudinal observational cohort studies in cancer patients are important to move research and clinical practice forward. Continued study participation (study retention) is of importance to maintain the statistical power of research and facilitate representativeness of study findings. This study aimed to investigate study retention and attrition (drop-out) and its associated sociodemographic and clinical factors among head and neck cancer (HNC) patients and informal caregivers included in the Netherlands Quality of Life and Biomedical Cohort Study (NET-QUBIC)., Methods: NET-QUBIC is a longitudinal cohort study among 739 HNC patients and 262 informal caregivers with collection of patient-reported outcome measures (PROMs), fieldwork data (interview, objective tests and medical examination) and biobank materials. Study retention and attrition was described from baseline (before treatment) up to 2-years follow-up (after treatment). Sociodemographic and clinical characteristics associated with retention in NET-QUBIC components at baseline (PROMs, fieldwork and biobank samples) and retention in general (participation in at least one component) were investigated using Chi-square, Fisher exact or independent t-tests (p< 0.05)., Results: Study retention at 2-years follow-up was 80% among patients alive (66% among all patients) and 70% among caregivers of patients who were alive and participating (52% among all caregivers). Attrition was most often caused by mortality, and logistic, physical, or psychological-related reasons. Tumor stage I/II, better physical performance and better (lower) comorbidity score were associated with participation in the PROMs component among patients. No factors associated with participation in the fieldwork component (patients), overall sample collection (patients and caregivers) or PROMs component (caregivers) were identified. A better performance and comorbidity score (among patients) and higher age (among caregivers) were associated with study retention at 2-years follow-up., Conclusions: Retention rates were high at two years follow-up (i.e. 80% among HNC patients alive and 70% among informal caregivers with an active patient). Nevertheless, some selection was shown in terms of tumor stage, physical performance, comorbidity and age, which might limit representativeness of NET-QUBIC data and samples. To facilitate representativeness of study findings future cohort studies might benefit from oversampling specific subgroups, such as patients with poor clinical outcomes or higher comorbidity and younger caregivers., (© 2022. The Author(s).)

Background: Accurate identification of older persons at risk of unplanned hospital visits can facilitate preventive interventions. Several risk scores have been developed to identify older adults at risk of unplanned hospital visits. It is unclear whether risk scores developed in one country, perform as well in another. This study validates seven risk scores to predict unplanned hospital admissions and emergency department (ED) visits in older home care recipients from six countries., Methods: We used the IBenC sample (n = 2446), a cohort of older home care recipients from six countries (Belgium, Finland, Germany, Iceland, Italy and The Netherlands) to validate four specific risk scores (DIVERT, CARS, EARLI and previous acute admissions) and three frailty indicators (CHESS, Fried Frailty Criteria and Frailty Index). Outcome measures were unplanned hospital admissions, ED visits or any unplanned hospital visits after 6 months. Missing data were handled by multiple imputation. Performance was determined by assessing calibration and discrimination (area under receiver operating characteristic curve (AUC))., Results: Risk score performance varied across countries. In Iceland, for any unplanned hospital visits DIVERT and CARS reached a fair predictive value (AUC 0.74 [0.68-0.80] and AUC 0.74 [0.67-0.80]), respectively). In Finland, DIVERT had fair performance predicting ED visits (AUC 0.72 [0.67-0.77]) and any unplanned hospital visits (AUC 0.73 [0.67-0.77]). In other countries, AUCs did not exceed 0.70., Conclusions: Geographical validation of risk scores predicting unplanned hospital visits in home care recipients showed substantial variations of poor to fair performance across countries. Unplanned hospital visits seem considerably dependent on healthcare context. Therefore, risk scores should be validated regionally before applied to practice. Future studies should focus on identification of more discriminative predictors in order to develop more accurate risk scores., (© 2021. The Author(s).)

Background: Unusual sexual interests are largely intercorrelated, yet not much is known about underlying patterns of clusters between various sexual interests., Aim: To identify underlying clusters of unusual sexual interests using exploratory factor analysis., Methods: We conducted exploratory factor analysis with self-reported interest in a wide variety of unusual sexual acts for an online, international sample (N = 669; 61% female), and for women and men separately. Factor regression weights were correlated to self-reported sex life satisfaction, sexual outlet, and psychiatric symptoms., Outcomes: Participants rated the attractiveness of 50 unusual sexual activities, and reported on their sex life satisfaction (Arizona Sexual Experiences Scale), sexual outlet, and symptoms regarding ADHD (Adult ADHD Self-Report Screening Scale for DSM-5), depression, anxiety, and stress (Depression, Anxiety, and Stress Scale)., Results: We identified 5 factors of unusual sexual interests that were largely comparable for women and men: submission/masochism, forbidden sexual activities, dominance/sadism, mysophilia (attraction to dirtiness or soiled things), and fetishism. For women, unusual sexual interests related to more psychiatric symptoms and higher sexual outlet, whereas this relation was less explicit for men., Clinical Implications: Different factors of unusual sexual interests may serve different underlying functions or motivations, for instance related to sexual, and emotional regulation. A better understanding of the nature of unusual sexual interests is important to be able to influence sexual interests that are unwanted or cause damage to others., Strengths & Limitations: Strength of this study include its anonymity, the avoidance of sexual orientation effects, and the possibility to indicate only a slight endorsement toward sexual items. Limitations include the sample's generalizability and the truthfulness of online responding., Conclusion: Unusual sexual interests could be clustered into 5 factors that were largely comparable for women and men: submission/masochism, forbidden sexual activities, dominance/sadism, mysophilia, and fetishism. Schippers EE, Smid WJ, Huckelba AL, et al. Exploratory Factor Analysis of Unusual Sexual Interests. J Sex Med 2021;18:1615-1631., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Attachment (mal)functioning and a history of childhood trauma (CT) are both considered psychological determinants of personality disorders (PDs). Their interaction, however, remains largely uninvestigated. In this study, the authors assessed adult and childhood attachment style in a sample of patients with diverse PDs ( N = 75) and determined the relation with both occurrence and severity of CT. The authors found that the sample was characterized by severe attachment malfunctioning and high levels of CT. Using cross-tabulations and analysis of variance, the authors showed that patients with a fearful or dismissive attachment style experienced more severe CT than patients with a preoccupied attachment style. Patients reporting an affectionless control bonding style to either parent suffered frequent and severe CT. Although temporal causality cannot be determined, these findings stress the necessity to screen for CT in PDs and suggest that attachment-centered psychotherapy for these patients may benefit from preceding or concurrent trauma treatment.

Background: Although depression is typically characterized by a persistent depressed mood, mood dynamics do seem to vary across a depressed population. Heterogeneity of mood variability (magnitude of changes) and emotional inertia (speed at which mood shifts) is seen in clinical practice. However, studies investigating the heterogeneity of these mood dynamics are still scarce. The aim of the present study is to explore different distinctive profiles in real-time monitored mood dynamics among depressed persons., Methods: After completing baseline measures, mildly-to-moderately depressed persons ( n  = 37) were prompted to rate their current mood (1-10 scale) on their smartphones, 3 times a day for 7 consecutive days. Latent profile analyses were applied to identify profiles based on average mood, variability of mood and emotional inertia as reported by the participants., Results: Two profiles were identified in this sample. The overwhelming majority of the sample belonged to profile 1 ( n  = 31). Persons in profile 1 were characterized by a mood just above the cutoff for positive mood (M = 6.27), with smaller mood shifts (lower variability [SD = 1.05]) than those in profile 2 ( n  = 6), who displayed an overall negative mood (M = 4.72) and larger mood shifts (higher variability [SD = 1.95]) but at similar speed (emotional inertia) (AC = 0.19, AC = 0.26, respectively)., Conclusions: The present study provides preliminary indications for patterns of average mood and mood variability, but not emotional inertia, among mildly-to-moderately depressed persons., Competing Interests: None., (© 2021 The Authors.)

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

Purpose: The level of daily physical activity in patients with cancer is frequently assessed by questionnaires, such as the Physical Activity Scale for the Elderly (PASE). Objective assessments, with for example accelerometers, may be a good alternative. The aim of this study was to investigate the agreement between the PASE questionnaire and accelerometer-assessed physical activity in a large group of patients with different types of cancer., Methods: Baseline accelerometer and PASE questionnaire data of 403 participants from the REACT (Resistance and Endurance Exercise After Chemotherapy, n = 227), the EXIST (Exercise Intervention After Stem-Cell Transplantation, n = 74), and NET-QUBIC (NEtherlands QUality of Life And Biomedical Cohort Studies In Cancer, n = 102) studies were available for the current analyses. Physical activity was assessed by the PASE questionnaire (total score) and accelerometers (total minutes per day > 100 counts). Linear mixed models regression analysis was used to assess the agreement between the PASE questionnaire and accelerometer-assessed physical activity., Results: The mean (SD) PASE score was 95.9 (75.1) points and mean (SD) time in physical activity measured with the accelerometer was 256.6 (78.8) min per day. The agreement between the PASE score and the accelerometer data was significant, but poor (standardized regression coefficient (B) = 0.36, 95%CI = 0.27; 0.44, p < 0.01)., Conclusion: Agreement between the PASE questionnaire and accelerometer-assessed physical activity was poor. The poor agreement indicates that they measure different physical activity constructs and cannot be used interchangeably to assess the level of daily physical activity in patients with cancer.

Background: The System Usability Scale (SUS) is used to measure usability of internet-based Cognitive Behavioural Therapy (iCBT). However, whether the SUS is a valid instrument to measure usability in this context is unclear. The aim of this study is to assess the factor structure of the SUS, measuring usability of iCBT for depression in a sample of professionals. In addition, the psychometric properties (reliability, convergent validity) of the SUS were tested., Methods: A sample of 242 professionals using iCBT for depression from 6 European countries completed the SUS. Confirmatory Factor Analysis (CFA) was conducted to test whether a one-factor, two-factor, tone-model or bi-direct model would fit the data best. Reliability was assessed using complementary statistical indices (e.g. omega). To assess convergent validity, the SUS total score was correlated with an adapted Client Satisfaction Questionnaire (CSQ-3)., Results: CFA supported the one-factor, two-factor and tone-model, but the bi-factor model fitted the data best (Comparative Fit Index = 0.992, Tucker Lewis Index = 0.985, Root Mean Square Error of Approximation = 0.055, Standardized Root Mean Square Residual = 0.042 (respectively χ 2 diff (9) = 69.82, p < 0.001; χ 2 diff (8) = 33.04, p < 0.001). Reliability of the SUS was good (ω = 0.91). The total SUS score correlated moderately with the CSQ-3 (CSQ1 r s  = .49, p < 0.001; CSQ2 r s  = .46, p < 0.001; CSQ3 r s  = .38, p < 0.001), indicating convergent validity., Conclusions: Although the SUS seems to have a multidimensional structure, the best model showed that the total sumscore of the SUS appears to be a valid and interpretable measure to assess the usability of internet-based interventions when used by professionals in mental healthcare.

Introduction: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) introduced a dissociative subtype for patients with posttraumatic stress disorder (PTSD) and depersonalization and/or derealization symptoms. Despite high comorbidity rates between PTSD and dissociative disorders (DDs), research has not paid attention to the differentiation or overlap between the dissociative subtype of PTSD and DDs. This raises a question: To what extent do patients with dissociative PTSD differ from patients with PTSD and comorbid DDs?, Method: We compared three groups of complex patients with trauma-related disorders and/or personality disorders (n = 150): a dissociative PTSD, a nondissociative PTSD, and a non-PTSD group of patients with mainly personality disorders. We used structured clinical interviews and self-administered questionnaires on dissociative symptoms and disorders, personality disorders, trauma histories, depression, anxiety, and general psychopathology. The Dissociative Experiences Scale (DES; ≥20) and the depersonalization/derealization subscale of the DES were used for differentiating dissociative PTSD from nondissociative PTSD., Results: Of all patients, 33% met criteria for dissociative PTSD. More than half of the dissociative PTSD patients (54%) met criteria for one or more DDs; using the depersonalization/derealization subscale of the DES, even 66% had a comorbid DD. But also of the non-PTSD patients, 24% had a mean DES score of ≥20. There were no symptomatic differences (e.g., depression and anxiety) between dissociative PTSD with and without comorbid DDs., Conclusion: Overlap between dissociative PTSD and DD is large and we recommend replication of previous studies, using structured clinical assessment of DDs. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Objective: Profiling patients who report early childhood trauma and emotional neglect may be useful for treatment planning. This study attempts to quantify a two-dimensional "trauma-neglect model" (Draijer, 2003) proposed to distinguish clinical profiles in terms of trauma-related, dissociative, and personality pathology., Method: A sample of patients referred to a trauma program ( n = 49) and a personality disorders program ( n = 101) was extensively assessed. Cluster analysis was used to discriminate patients in terms of "psychiatric disease burden," based on symptom severity scores, type of disorder, and level of maladaptive personality functioning. Clusters that differed in psychiatric disease burden were mapped in the trauma-neglect space and their positions were evaluated., Results: We found three clusters and labeled them as "mildly impaired" (26% of patients), "moderately impaired" (43% of patients), and "severely impaired" (31% of patients). The mean scores on trauma and neglect for the mild and severe groups differed significantly., Conclusions: These findings indicate that further investigation of the validity of the model, which may be used to plan treatment, is useful. Patients experiencing a wide range of trauma-related disorders, dissociative disorders (DD), and personality disorders (PD), combined with a high level of psychiatric symptoms and a maladaptive style of personality functioning, report a range of traumatic experiences in combination with a lack of maternal care, and can be profiled as "severely impaired." (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: To assess the efficacy of bright light therapy (BLT) in reducing depressive symptoms in patients with Parkinson disease (PD) and major depressive disorder (MDD) compared to a control light., Methods: In this double-blind controlled trial, we randomized patients with PD and MDD to treatment with BLT (±10,000 lux) or a control light (±200 lux). Participants were treated for 3 months, followed by a 6-month naturalistic follow-up. The primary outcome of the study was the Hamilton Depression Rating Scale (HDRS) score. Secondary outcomes were objective and subjective sleep measures and salivary melatonin and cortisol concentrations. Assessments were repeated halfway, at the end of treatment, and 1, 3, and 6 months after treatment. Data were analyzed with a linear mixed-model analysis., Results: We enrolled 83 participants. HDRS scores decreased in both groups without a significant between-group difference at the end of treatment. Subjective sleep quality improved in both groups, with a larger improvement in the BLT group (B [SE] = 0.32 [0.16], p = 0.04). Total salivary cortisol secretion decreased in the BLT group, while it increased in the control group (B [SE] = -8.11 [3.93], p = 0.04)., Conclusion: BLT was not more effective in reducing depressive symptoms than a control light. Mood and subjective sleep improved in both groups. BLT was more effective in improving subjective sleep quality than control light, possibly through a BLT-induced decrease in cortisol levels., Clinicaltrialsgov Identifier: NCT01604876., Classification of Evidence: This study provides Class I evidence that BLT is not superior to a control light device in reducing depressive symptoms in patients with PD with MDD., (© 2019 American Academy of Neurology.)

Background: Suicidality could be associated with specific combinations of biological, social and psychological factors. Therefore, depressive episodes with suicidal ideation could be different from depressive episodes without suicidal ideation in terms of latent variable structures., Methods: In this study we compared latent variable structures between suicidal and non-suicidal depressed patients using confirmatory factor analysis (CFA), following a measurement invariance test procedure. Patients (N = 919) suffering from major depressive disorder were selected from the Netherlands Study of Depression and Anxiety (NESDA) and split into a group that showed no symptoms of suicidal ideation (non-SI; N = 691) and a suicidal ideation (SI) group that had one or more symptoms of suicidal ideation (N = 228). Depression and anxiety symptoms were measured using the short form of the Mood and Anxiety Symptoms Questionnaire (MASQ-D30)., Results: CFA implied a difference in latent variable structures between the non-SI sample (CFI 0.957; RMSEA 0.041) and the SI sample (CFI 0.900; RMSEA 0.056). Subsequent multiple-group CFA showed violations of measurement invariance. The General distress and Anhedonic depression subscales were best indicated by hopelessness and lack of optimism in the SI sample and by dissatisfaction and not feeling lively in the non-SI sample. Overall, the SI sample had higher scores and lower inter-item correlations on the Anhedonic depression items., Limitations: We have included very mild cases of suicidal ideation in our SI sample., Conclusions: On a latent variable level, depression with suicidal ideation differs from depression without suicidal ideation. Results encourage further research into the symptom structure of depression among suicidal patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: In the Netherlands, a great variety of objectively measured geo-data is available, but these data are scattered and measured at varying spatial and temporal scales. The centralisation of these geo-data and the linkage of these data to individual-level data from longitudinal cohort studies enable large-scale epidemiological research on the impact of the environment on public health in the Netherlands. In the Geoscience and Health Cohort Consortium (GECCO), six large-scale and ongoing cohort studies have been enriched with a variety of existing geo-data. Here, we introduce GECCO by describing: (1) the phenotypes of the involved cohort studies, (2) the collected geo-data and their sources, (3) the methodology that was used to link the collected geo-data to individual cohort studies, (4) the similarity of commonly used geo-data between our consortium and the nationwide situation in the Netherlands and (5) the distribution of geo-data within our consortium., Participants: GECCO includes participants from six prospective cohort studies (eg, 44 657 respondents (18-100 years) in 2006) and it covers all municipalities in the Netherlands. Using postal code information of the participants, geo-data on the address-level, postal code-level as well as neighbourhood-level could be linked to individual-level cohort data., Findings to Date: The geo-data could be successfully linked to almost all respondents of all cohort studies, with successful data-linkage rates ranging from 97.1% to 100.0% between cohort studies. The results show variability in geo-data within and across cohorts. GECCO increases power of analyses, provides opportunities for cross-checking and replication, ensures sufficient geographical variation in environmental determinants and allows for nuanced analyses on specific subgroups., Future Plans: GECCO offers unique opportunities for (longitudinal) studies on the complex relationships between the environment and health outcomes. For example, GECCO will be used for further research on environmental determinants of physical/psychosocial functioning and lifestyle behaviours., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: It remains difficult to predict and prevent suicidal behaviour, despite growing understanding of the aetiology of suicidality. Clinical guidelines recommend that health care professionals develop a safety plan in collaboration with their high-risk patients, to lower the imminent risk of suicidal behaviour. Mobile health applications provide new opportunities for safety planning, and enable daily self-monitoring of suicide-related symptoms that may enhance safety planning. This paper presents the rationale and protocol of the Continuous Assessment for Suicide Prevention And Research (CASPAR) study. The aim of the study is two-fold: to evaluate the feasibility of mobile safety planning and daily mobile self-monitoring in routine care treatment for suicidal patients, and to conduct fundamental research on suicidal processes., Methods: The study is an adaptive single cohort design among 80 adult outpatients or day-care patients, with the main diagnosis of major depressive disorder or dysthymia, who have an increased risk for suicidal behaviours. There are three measurement points, at baseline, at 1 and 3 months after baseline. Patients are instructed to use their mobile safety plan when necessary and monitor their suicidal symptoms daily. Both these apps will be used in treatment with their clinician., Conclusion: The results from this study will provide insight into the feasibility of mobile safety planning and self-monitoring in treatment of suicidal patients. Furthermore, knowledge of the suicidal process will be enhanced, especially regarding the transition from suicidal ideation to behaviour.The study protocol is currently under revision for medical ethics approval by the medical ethics board of the Vrije Universiteit Medical centre Amsterdam (METc number 2017.512/NL62795.029.17).

The molecular mechanisms causing smoking-induced health decline are largely unknown. To elucidate the molecular pathways involved in cause and consequences of smoking behavior, we conducted a genome-wide gene expression study in peripheral blood samples targeting 18 238 genes. Data of 743 smokers, 1686 never smokers and 890 ex-smokers were available from two population-based cohorts from the Netherlands. In addition, data of 56 monozygotic twin pairs discordant for ever smoking were used. One hundred thirty-two genes were differentially expressed between current smokers and never smokers (P < 1.2 × 10 -6 , Bonferroni correction). The most significant genes were G protein-coupled receptor 15 (P < 1 × 10 -150 ) and leucine-rich repeat neuronal 3 (P < 1 × 10 -44 ). The smoking-related genes were enriched for immune system, blood coagulation, natural killer cell and cancer pathways. By taking the data of ex-smokers into account, expression of these 132 genes was classified into reversible (94 genes), slowly reversible (31 genes), irreversible (6 genes) or inconclusive (1 gene). Expression of 6 of the 132 genes (three reversible and three slowly reversible) was confirmed to be reactive to smoking as they were differentially expressed in monozygotic pairs discordant for smoking. Cis-expression quantitative trait loci for GPR56 and RARRES3 (downregulated in smokers) were associated with increased number of cigarettes smoked per day in a large genome-wide association meta-analysis, suggesting a causative effect of GPR56 and RARRES3 expression on smoking behavior. In conclusion, differential gene expression patterns in smokers are extensive and cluster in several underlying disease pathways. Gene expression differences seem mainly direct consequences of smoking, and largely reversible after smoking cessation. However, we also identified DNA variants that may influence smoking behavior via the mediating gene expression., (© 2015 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Depression and anxiety have been related to poorer self-reported physical functioning over time; however, objective measures of physical function are less frequently examined. This study assessed the 6-year trajectory of hand-grip strength and lung function in persons with depressive and/or anxiety disorders., Methods: At four waves (baseline, 2, 4, and 6 years) hand-grip strength and lung function were assessed in 2,480 participants, aged 18-65 years, of the Netherlands Study of Depression and Anxiety. Linear mixed models were used to examine the association between baseline psychiatric status (current and remitted depression and anxiety, healthy controls) and physical function during 6-year follow-up, adjusted for sociodemographics, lifestyle, and health indicators., Results: Although there were no differences in the rate of decline over time, women with current, but not remitted, depression and anxiety had poorer hand-grip strength (B = -1.34, P < .001) and poorer lung function (B = -11.91, P =.002) compared to healthy women during the entire 6-year follow-up. Associations with depression and anxiety severity measures confirmed dose-response relationships with objective physical function. In men, stronger 6-year decline of lung function was found in those with current disorders (current diagnosis-by-time: B = -11.72, P = .002) and even in those with remitted disorders (remitted diagnosis by time: B = -10.11, P = .04) compared to healthy men., Conclusions: Depression and anxiety are associated with consistently poorer hand-grip strength in women and poorer lung function in women and men over 6 years of time, implicating their long-lasting impact on physical functioning., (© 2016 Wiley Periodicals, Inc.)

Introduction: Although older adults are just as likely to benefit from e-mental health as their younger counterparts, there are virtually no applications specifically designed to accommodate the needs of older adults with recurrent depression or bipolar disorder. Recurrent mood disorders constitute a large and rising proportion of the global disease in older populations, indicating a need for more e-mental health applications targeting this group. This paper describes the theoretical background and methodology of a study examining the feasibility of a tablet-based self-management platform for older adults with recurrent mood disorders. The eCare@Home platform was designed to 1) improve patients' awareness and knowledge of recurrent mood disorders and their treatment, 2) promote self-management through the use of a simple daily monitoring tool, and 3) facilitate online contact with their clinician through videoconferencing., Methods: The design involves a single-group four-month pilot study, with measurements at baseline (T0), and at weeks 8 and 16 (T1 and T2). The target group consists of older outpatients (aged 60 or above) who are undergoing treatment for recurrent depressive or bipolar disorder (N = 50), and their clinicians (N = 10). Primary feasibility endpoints will be system acceptability, system usability, and client satisfaction with the platform. In addition, qualitative data from semi-structured interviews in N = 10 patients and N = 5 clinicians will be gathered to provide more insight into user experiences and evaluations of the platform's added value., Discussion: To the best of our knowledge, this is the first study to evaluate the feasibility and acceptability of a tablet-based e-mental health platform for older adults with severe mood disorders. If tablet-based support for this group is shown to be feasible, the intention is to proceed with the design of a large-scale process and outcome evaluation. The strengths and limitations of the methodology used are addressed in this article. Trial R egistration: registration is pending.

[This corrects the article DOI: 10.1371/journal.pgen.1005378.].

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Estimates of the extent of childhood sexual abuse (CSA) within in the Roman Catholic Church (RCC) in the general population are difficult to find. The independent Commission of Inquiry into sexual abuse of minors in the RCC in the Netherlands collected population-based data to estimate its prevalence. A large random online population sample was surveyed using a two-phase stratified sampling procedure. In Phase 1, 34,267 subjects aged 40 years and older were screened for childhood exposure to sexual abuse by non-family members, a history of institutionalization and a Roman Catholic upbringing. In Phase 2, a stratified subset of 2,462 subjects was assessed to obtain more detailed target information about sexual abuse reports within the RCC. We employed multiple imputation for the estimation of RCC CSA in the original Phase 1 sample. The prevalence of non-familial CSA in general (14.0%) was higher among women (17.2%) than among men (10.6%). The prevalence of CSA within the Dutch RCC (1.7%) was higher among men (2.7%) than among women (0.7%). As expected, older subjects reported more often CSA in the RCC than their younger counterparts. Respondents who stayed for some time in RCC run institutions for education or child protection had a higher risk to report sexual abuse. Although sexual abuse of minors by representatives of the RCC was a structural problem during a period that the Church was highly influential in the Netherlands, the estimated prevalence of the phenomenon is only a fraction of the prevalence rate of non-familial CSA., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Epidemiological research on childhood sexual abuse (CSA) and its consequences in adult life mainly relies on retrospective reports. This study explores their consistency and the correlates of inconsistent CSA self-reports in a random population sample., Method: A stratified subsample of 2,462 subjects (selected from a large-scale (N = 34,267) representative sample of Dutch adults aged 40 and beyond) participated in a two-phase online questionnaire survey on extra-familial CSA which was conducted on a four- to six-week interval. Subjects reporting CSA were overrepresented. Participants with consistent and inconsistent responses were compared with regard to demographics, family background, abuse severity, and clinical characteristics. Potential correlates of inconsistency were identified using logistic regression analysis. An additional questionnaire (Phase III) administered to inconsistent respondents explored possible reasons for their inconsistency., Results: Of the 1,992 respondents who had reported extra-familial CSA during Phase I, 707 (35.5%) denied this in Phase II. Of the 2,462 respondents in Phase II, 727 (29.5%; 9.2% when considering sample stratification) gave a discrepant answer to the extra-familial sexual abuse item compared to their answers given in Phase I. Reports of less severe abuse, intra-familial CSA, and early parental separation predicted inconsistency. Reasons provided for inconsistency varied from misunderstanding (e.g., reporting intra-familial CSA rather than extra-familial CSA) to emotional motives (e.g., embarrassment, being overwhelmed) or practical considerations (e.g., lack of privacy while filling out the questionnaire)., Conclusions: Inconsistent self-reports of extra-familial sexual abuse occur on a substantial scale and are associated with less severe forms of abuse (lack of salience) or classification difficulties (perpetrator being a family member or not). Consistency tests and probing for clarifications or corrections should be routinely conducted in order to increase the quality of CSA epidemiological research.

Introduction: Anxiety disorders are highly prevalent in patients with Parkinson's disease (PD) and have a major impact on wellbeing. They nevertheless receive limited scientific attention. This study aimed to establish the symptom dimensions of anxiety in PD, and their relationship with depression, autonomic failure and motor symptoms., Methods: In this cross-sectional observational study, symptoms of anxiety were measured with the Beck Anxiety Inventory (BAI) in 294 PD patients. Symptom dimensions of anxiety in PD were explored through principal component analysis (PCA) of BAI items. The relationship between anxiety and depressive, autonomic and motor symptoms was assessed through PCA and regression analyses., Results: Clinically relevant symptoms of anxiety were present in 45% of patients. PCA of the BAI resulted in five subscales, corresponding to a single affective and four somatic symptom dimensions (thermoregulation, hypotension, hyperventilation and trembling) of anxiety. Symptoms of anxiety and depression displayed a large overlap. All somatic BAI subscales were significantly influenced by motor and autonomic symptoms, while the affective subscale was not., Conclusion: Anxiety in PD comprises affective and somatic symptom dimensions. The affective subscale of the BAI is not influenced by motor or autonomic symptoms, and may therefore prove useful for future research. Scores on the somatic subscales of the BAI were associated with autonomic failure and motor impairment, demonstrating a strong interplay between motor and non-motor symptoms in PD. These results stress the importance of a holistic approach of anxiety in PD., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Subclinical depression is common. Although interventions have proven to be effective, participation rates are low. This study first aimed to get more insight in help-seeking and reasons for (not) seeking care. The second aim was to identify characteristics that distinguish people who receive help, those with an unmet need, or no perceived need for care., Methods: Respondents with a subclinical depression (n=162) were recruited from the general population. They were eligible for participation if they were aged 18 years or older, scored 20 or higher on the K10 screening instrument for depression, and did not meet the criteria for major depression., Results: Of all participants, 27% received help, 33% had an unmet need, and 40% had no perceived need for care. Participants with no perceived need reported not to experience symptoms, were able to solve problems on their own, and could mobilize their own support. They were characterized by lower scores on neuroticism and an older age than those who received care., Limitations: The response rate in this study was relatively low which may have caused a selection bias., Conclusion: Not all people with subclinical depression may need help for their symptoms, some are able to deal with problems on their own. However, others experience a need for care but do not receive any. Gaining insight into potential barriers for help seeking and receiving in people with an unmet need is important so appropriate measures can be taken to ensure that those who need care get the help they want., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: Large cohort studies are needed taking into account cancer-related, personal, biological, psychobehavioral, and lifestyle-related factors, to guide future research to improve treatment and supportive care. We aimed to evaluate the feasibility of a comprehensive baseline assessment of a cohort study evaluating the course of quality of life (QoL)., Methods: Newly diagnosed head and neck cancer (HNC) patients were asked to participate. Assessments consisted of questionnaires (635 items), a home visit (including a psychiatric interview, physical tests, and blood and saliva collection), and tissue collection. Representativeness of the study sample was evaluated by comparing demographics, clinical factors, depression, anxiety, and QoL between responders and non-responders. Feasibility was evaluated covering the number of questions, time investment, intimacy, and physical burden., Results: During the inclusion period (4 months), 15 out of 26 (60 %) patients agreed to participate. Less women participated, 13 % in responders group versus 63 % in non-responders group (p = 0.008). No other differences were found between responders and non-responders. Responders completed more than 95 % of the questionnaires' items and rated the number of questions, time investment and intimacy as feasible, and the physical and psychological burden as low. It took on average 3 h to complete the questionnaires and 1.5 h for the home visit., Conclusions: This study reveals that a comprehensive assessment including various questionnaires, physical measurements, and biological assessments is feasible according to patients with newly diagnosed HNC. A large prospective cohort study has started aiming to include 739 HNC patients and their informal caregivers in the Netherlands.

Objective: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date., Method: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios., Results: Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%)., Conclusion: Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures., Competing Interests: The following authors have read the journal's policy and have the following conflicts: CLBu: Currently receiving funding for TS clinical trials from Otsuka Pharmaceutical, JFL: recevies research support from NIH and Grifols, LLC as well royalties from John Wiley and Sons, McGraw Hill, and Oxford University Press, MARic: received honoraria from Lundbeck, and research funding from Great-West Life Assurance Company of Canada and Eli Lilly Canada Ltd, MCR: grant from CNPq (Brazilian National Counsil) and has received research grants and/or consultancy honoraria from Novartis and Shire, DR: received consulting fees for Shire, JMS: received research support, honoraria and travel support from the Tourette Syndrome Association (TSA), DJS: received research grants and/or consultancy honoraria from Abbott, Astrazeneca, Biocodex, Eli-Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Takeda, Tikvah, and Wyeth, TVF: received research funding from NIMH (K08 MH099424-01), the Simons Foundation, Allison Foundation, and Shire, PS: received research support for this study from the Tourette Syndrome Association (TSA), Tourette Syndrome Foundation of Canada and NIH, DY: received research support from the Tourette Syndrome Association (TSA) and NIH, MMR: received grants from the Tourette's Action-UK, TSA-USA, honoraria from Janssen-Cilag, and book royalties from Wiley - Blackwell, David Fulton/Granada/Taylor Francis, Oxford University Press and Jessica Kingsley Publishers, is a Patron of Tourette's Action (UK), sits on the Medical Advisory Board of the Italian Tourette Syndrome Association and The Tourette Syndrome Foundation of Canada, DAC: NIH/NIMH funding for K01 MH072952 and R34 MH090149, SLR: participated in research funded by Medtronic and Cyberonics, JRW: Past employee of F. Hoffmann-La Roche and current employee of Pfizer, SW: received lecture honoraria from Janssen Cilag, AstraZeneca and Eli Lilly, research funds Swiss National Science Foundation (SNF), Deutsche Forschungsgemeinschaft, EU FP7, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, JV: funding from Seaside Therapeutics, Novartis, Roche Pharmaceuticals, Forest, and SynapDx. Consulting/Advisory Board for Novartis, JTM: Tourette Syndrome Association-Speaker honoraria; Otuska-research grant; Roche-consultant; 1R01MH079487-01A1, JLK: honoraria from Roche, Eli Lilly, and Novartis, PDA: Unrestricted research grant from DNA Genotek SLG, HJG, ML, DLP, SES, NL, JHS, CLBa, LB, FB, GBB, OJB, MHB, RMB, RDB, DC, CC, JCCS, DCC, MCC, SC, DVC, EHC, VC, NJC, BAC, LKD, DDen, DDef, RD, EMD, YD, CKE, KE, PF, NBF, PJG, ERG, HG, MAG, BDG, VGT, SH, GLH, GAH, SMJH, PH, AGH, CI, JJ, MAJ, CLK, RAK, JAK, AIK, BK, RK, SHL, LL, CLi, CLo, TLL, FM, CAM, LMM, WM, SCMR, ECM, RM, JM, HM, DLM, ALN, BMN, GN, HN, WCO, BAO, RAO, LO, AJP, MTP, CNP, CP, YP, DP, TJR, VIR, MARid, GAR, SR, ARL, ASS, JS, BS, HSS, ES, JAT, AVVD, HV, MW, YW, JY, HGMW, PE, BC, RR have declared that no competing interests exist.

Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach., Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n  =  198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p < 0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p < 0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p  =  0.001)., Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.

Introduction: Depressive and anxiety disorders often involve a chronic course. This study examined whether objective physical function is a predictor for the persistence of depressive and anxiety disorders., Method: The study sample consisted of 1206 persons with depressive and anxiety disorders at baseline. Hand grip strength and lung function were used as objective physical function measurements and were determined at baseline. Outcome variable was a 6-month depressive and/or anxiety diagnosis after 2 years of follow-up., Results: Lower hand grip strength predicted the persistence of depressive and/or anxiety disorders at 2-year follow-up (per SD increase: OR=0.82, CI: 0.69-0.99, p=0.04). Associations were consistent for depressive and anxiety disorder persistence. Poorer lung function was associated with the persistence of depressive disorders (per SD increase: OR=0.83, CI: 0.70-0.98, p=0.03) but not with anxiety disorders., Limitations: Follow-up was limited to 2 years., Conclusions: Objectively measured poorer physical function predicted the persistence of depressive and/or anxiety disorders., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Poorer physical function in patients with depressive or anxiety disorders has been reported, but is often measured by self-reports which may be biased by mood. This study examined the association between depression and anxiety and physical function using objective measures in a large cohort, and investigated which psychiatric characteristics are associated with physical function., Methods: Baseline data from the Netherlands Study of Depression and Anxiety were used, including persons with current depressive and/or anxiety disorders (n = 1629) and healthy controls without lifetime diagnoses (n = 629). Psychiatric characteristics studied included type of disorder, duration, severity, age of onset, and antidepressant use. Hand grip strength and lung function were used as general objective measurements of physical function., Results: Women with depressive or anxiety disorders had significantly poorer physical function - both lower grip strength and lung function - compared to healthy controls, especially those with a late age of onset (≥ 40 years). Poorer lung function was present among the women using antidepressants, those with higher symptom severity, and those with depression compared to anxiety disorder. In men, depressive or anxiety disorder was associated with better lung function but not with hand grip strength., Limitations: Due to the cross-sectional design no causal relationships could be established., Conclusions: In women, depressive or anxiety disorders were associated with objective indicators of poorer physical function. Since this association was most pronounced for later onset disorders, it suggests a larger role of physical function in depressive and anxiety disorders at later age., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Background: Cortisol levels are increasingly often assessed in large-scale psychosomatic research. Although determinants of different salivary cortisol indicators have been described, they have not yet been systematically studied within the same study with a large sample size. Sociodemographic, health and sampling-related determinants of salivary cortisol levels were examined in a sample without potential disturbances because of psychopathology., Methods: Using 491 respondents (mean age=43.0 years, 59.5% female) without lifetime psychiatric disorders from the Netherlands Study of Depression and Anxiety (NESDA), sociodemographic, sampling and health determinants of salivary cortisol levels were examined. Respondents collected seven salivary cortisol samples providing information about 1-h awakening cortisol, diurnal slope, evening cortisol and a dexamethasone (0.5mg) suppression test (DST)., Results: Higher overall morning cortisol values were found for smokers, physically active persons, persons without cardiovascular disease, sampling on a working day or in a month with less daylight. In addition, the cortisol awakening response was significantly flattened for males, persons with cardiovascular disease, those with late awakening times and those with longer sleep duration. Diurnal slope was steeper in men, physically active persons, late awakeners, working persons, and season with less daylight. A higher evening cortisol level was associated with older age, smoking and season with more daylight. Cortisol suppression after dexamethasone ingestion was found to be less pronounced in smokers, less active persons and sampling on a weekday., Conclusion: Sociodemographic variables (sex, age), sampling factors (awakening time, working day, sampling month, sleep duration) and health indicators (smoking, physical activity, cardiovascular disease) were shown to influence different features of salivary cortisol levels. Smoking had the most consistent effect on all cortisol variables. These factors should be considered in psychoneuroendocrinology research.

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

To locate the genes that make a substantial contribution to variation in natural dizygotic twinning in humans, large-scale studies are needed. New studies should not stop at DNA genotyping, but collect material that allow gene-expression analysis, transcriptomics, proteomics and endocrinology. In this article we describe a pilot study to examine the feasibility, effectiveness and logistics of large-scale nationwide sample collection in Dutch families in which two or more sisters have given birth to spontaneous dizygotic twins. Pedigree data and addresses from family members of proband mothers were collected by telephone. Blood and urine samples were collected during a home visit, and handled in the afternoon. All participants were bled between 7 a.m. and 10 a.m. after overnight fasting. Blood samples of fertile women with a natural cycle were collected on the second, third or fourth day of their menstrual cycle. The effects of transportation and storage on blood quality, lipids, RNA with and without challenge, lymphocytes and other parameters were examined. Genomic DNA was isolated from blood and cells were immortalized using Epstein-Barr virus. In 78.6% of the women with a natural cycle blood samples were collected on the second, third or fourth day of the menstrual cycle. This percentage is likely to increase with the more dense geographical distribution of participants in the larger population. We conclude that the pilot study demonstrated the feasibility of this protocol to collect good quality of plasma, DNA, RNA and lymphocyte samples by home visits.

This article focuses on the assessment of competence of elderly persons both with and without cognitive impairment. In total 113 patients of a geriatric clinic were interviewed. Competence was assessed by using two clinical vignettes, representing respectively a hypothetical treatment situation with mild consequences (endoscopy) and one with severe consequences (operation for colon cancer). Competence was evaluated using the following standards: the ability to evidence a choice, the ability to understand a situation, the ability to reason about a choice, and the ability to appreciate a situation. In the vignette with mild consequences, elderly persons with cognitive impairment performed significantly worse on understanding, reasoning and appreciation than elderly persons without cognitive impairment. In the vignette with severe consequences, elderly persons with cognitive impairment performed significantly worse only on understanding as compared to elderly persons without cognitive impairment. No differences were found for reasoning and appreciation between the cognitively impaired and non-impaired elderly persons. We conclude that competence is less limited by cognitive impairment when assessed in a treatment situation with severe consequences. Therefore, the use of hypothetical vignettes should be carefully reconsidered.