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Background Several risk factors, among others lifestyle factors, have been suggested for hand eczema (HE). Objectives To investigate a possible association between HE and life style factors, including smoking, alcohol consumption, stress, body mass index (BMI), waist circumference, physical activity, diet and amount of sleep in the Dutch general population. Methods Data from the large population-based LifeLines Cohort Study was used. Individuals with HE in the past year were identified by a cross-sectional questionnaire in 2020. At baseline, information on lifestyle factors was collected. Results In total 57 046 individuals were included in the present analysis. Smoking ≥8 cigarettes/day, and smoking ≥15 pack years showed a positive association with HE in the past year. Also, chronic stress, a BMI > 30 kg/m2, and a waist circumference of >90 cm, were positively associated with HE in the past year. Conclusions The current study indicates that lifestyle factors are associated with HE. Advice regarding lifestyle factors might contribute to enhance overall health, of which HE might possibly benefit in conjunction. Further studies should also focus on the association between lifestyle factors and the severity and prognosis of HE rather than on occurrence alone. This article is protected by copyright. All rights reserved.

Epidemiological research has shown there to be a strong relationship between preconceptional, prenatal, birth and early-life factors and lifelong health. The Lifelines NEXT is a birth cohort designed to study the effects of intrinsic and extrinsic determinants on health and disease in a four-generation design. It is embedded within the Lifelines cohort study, a prospective three-generation population-based cohort study recording the health and health-related aspects of 167,729 individuals living in Northern Netherlands. In Lifelines NEXT we aim to include 1500 pregnant Lifelines participants and intensively follow them, their partners and their children until at least 1 year after birth. Longer-term follow-up of physical and psychological health will then be embedded following Lifelines procedures. During the Lifelines NEXT study period biomaterials—including maternal and neonatal (cord) blood, placental tissue, feces, breast milk, nasal swabs and urine—will be collected from the mother and child at 10 time points. We will also collect data on medical, social, lifestyle and environmental factors via questionnaires at 14 different time points and continuous data via connected devices. The extensive collection of different (bio)materials from mother and child during pregnancy and afterwards will provide the means to relate environmental factors including maternal and neonatal microbiome composition) to (epi)genetics, health and developmental outcomes. The nesting of the study within Lifelines enables us to include preconceptional transgenerational data and can be used to identify other extended families within the cohort.

Adverse childhood experiences (ACEs) are known to be closely related to depression, anxiety and sleep problems. However, it remains unclear whether adolescents with ACEs have sleep problems regardless of depression or anxiety or under a mediating effect from depression or anxiety. Therefore, our aim was to examine whether depression or anxiety mediates the relationship between ACEs and sleep problems in adolescents by using a community sample. The Early Trauma Inventory Self Report–Short Form (ETISR-SF) and List of Threatening Experiences Questionnaire (LTE-Q) were used to assess traumatic ACEs. Ultimately, data from 737 students (M = 448, F = 289, 15.1 ± 1.4 years old) were included in the statistical analysis. A total of 576 (78.1%) participants reported that they had experienced one or more ACEs. Adolescents with ACEs had higher levels of depression, anxiety and sleep problems than did adolescents without ACEs, and boys tended to experience more trauma than girls. Depression and anxiety partially mediated the relationship between ACEs and sleep problems. The results of this study suggest the need for depression and anxiety interventions for adolescents with ACEs to reduce the long-term consequences, including sleep problems and physical health problems.

The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (beta for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E * E interactions. © The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Background: Remitted depressed (RMD) individuals form a risk group for developing future depressive episodes. Improving cognitive control may reduce the risk to develop novel depressive symptoms, as beneficial effects of such training were demonstrated in RMD individuals. Method: The current study attempted to replicate and extend these results. In this randomized controlled trial (ClinicalTrials.gov NCT03278756), 68 RMD individuals were allocated to a cognitive control training or an active control condition, each comprised of 10 homework sessions dispersed over two weeks. Primary outcome measures were depressive symptomatology and rumination. Assessment took place before and after training and at 3 and 6 month follow-up. Results: This study showed training-related cognitive transfer and mixed effects on indicators of subjective cognitive functioning, depressive- and anxiety symptoms, as well as broader residual complaints. In addition, we failed to observe previously reported beneficial effects of CCT on indicators of emotion regulation and resilience. Conclusions: Given the partial replication of previously reported effects of cognitive control training in RMD, further research is needed.

Background: Neuropsychological alterations can lead to inaccurate perception, interpretation, and response to environmental information, which could be a risk factor for suicide. Methods: Ninety-six subjects were recruited from the Psychiatry Department of the Araba University Hospital-Santiago, including 20 patients with a recent attempt and diagnosis of major depressive disorder (MDD) according to DSM-V, 33 MDD patients with history of attempted suicide, 23 non-attempter MDD patients, and 20 healthy controls. All participants underwent a clinical interview and neuropsychological assessment on the following cognitive domains: working memory, processing speed, decision-making, executive function, and attention. Backward multiple regressions were performed adjusting for significant confounding variables. For group comparisons, ANOVA and Bonferroni post-hoc tests were performed with a p < 0.05 significance level. Results: The patient groups did not differ regarding severity of depression and stressful events in the last 6 months. In comparison to healthy controls, depressed patients with lifetime suicide attempts had more general trauma (p = 0.003), emotional abuse (p = 0.003), emotional negligence (p = 0.006), and physical negligence (p = 0.009), and depressed patients with recent suicide attempts had experienced more child sexual abuse (p = 0.038). Regarding neuropsychological assessment, all patient groups performed significantly worse than did healthy controls in processing speed, decision-making, and attention. Comparisons between patient groups indicated that recent suicide attempters had poorer performance on executive function in comparison to both depressed lifetime attempters and depressed non-attempters (B = 0.296, p = 0.019, and B = 0.301, p = 0.028, respectively). Besides, women with recent attempts had slightly better scores on executive function than males. Regarding the rest of the cognitive domains, there were no significant differences between groups. Conclusion: Executive function performance is altered in recent suicide attempts. As impaired executive function can be risk factor for suicide, preventive interventions on suicide should focus on its assessment and rehabilitation. This work was supported by Carlos III Health Research Institute [Grant Numbers PI15/00789, PI17/01433, PI18/01055, and PI19/00569 (co-financed by the European Regional Development Fund (ERDF)/European Social Fund Investing in your future, and the Government of the Principality of Asturias PCTI-2018-2022 IDI/2018/235). Foundation for Health Innovation and Research (BIOEF); Networking Center for Biomedical Research in Mental Health (CIBERSAM), the Basque Government (Grant No: 2017111104); and the University of the Basque Country (Grant No: 321218ELCY). The Psychiatric Research Department in Araba University Hospital is supported by the Stanley Research Foundation (Grant No: 03-RC-003). JF-S was a beneficiary of the PrePhD Training Programme of the Basque Government. No funding source in this study was involved in the study design, collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.

Purpose Negative life events (LEs) are associated with mental health problems in youth. However, little is known about underlying mechanisms. The aim of the study was to investigate whether exposure to LEs modifies stress sensitivity in youth’s daily life. Methods Ecological Momentary Assessment (EMA) was used to assess stress sensitivity (i.e., association of momentary stress with (i) negative affect and (ii) psychotic experiences) in 99 adolescents and young adults (42 service users, 17 siblings, and 40 controls; Mage 15 years). Before EMA, exposure to LEs (e.g., intrusive threats, experience of loss, serious illness) was assessed. Results Lifetime as well as previous-year exposure to LEs modified stress sensitivity in service users: they experienced more intense negative affect and psychotic experiences in response to stress when high vs. low exposure levels were compared. In contrast, controls showed no differences in stress sensitivity by exposure levels. Looking at specific types of LEs, controls showed less intense negative affect in response to stress when high vs. low exposure levels to threatening events during the last year, but not lifetime exposure, were compared. In siblings, no evidence was found that LEs modified stress sensitivity. Conclusion Stress sensitivity may constitute a putative risk mechanism linking LEs and mental health in help-seeking youth, while unfavourable effects of LEs on stress sensitivity may attenuate over time or do not occur in controls and siblings. Targeting individuals’ sensitivity to stress in daily life using novel digital interventions may be a promising approach towards improving youth mental health.

ObjectivesPatients who present in primary care with chronic functional somatic symptoms (FSS) have reduced quality of life and increased health care costs. Recognising these early is a challenge. The aim is to develop and internally validate a clinical prediction rule for repeated consultations with FSS.Design and settingRecords from the longitudinal population-based (‘Lifelines’) cohort study were linked to electronic health records from general practitioners (GPs).ParticipantsWe included patients consulting a GP with FSS within 1 year after baseline assessment in the Lifelines cohort.Outcome measuresThe outcome is repeated consultations with FSS, defined as ≥3 extra consultations for FSS within 1 year after the first consultation. Multivariable logistic regression, with bootstrapping for internal validation, was used to develop a risk prediction model from 14 literature-based predictors. Model discrimination, calibration and diagnostic accuracy were assessed.Results18 810 participants were identified by database linkage, of whom 2650 consulted a GP with FSS and 297 (11%) had ≥3 extra consultations. In the final multivariable model, older age, female sex, lack of healthy activity, presence of generalised anxiety disorder and higher number of GP consultations in the last year predicted repeated consultations. Discrimination after internal validation was 0.64 with a calibration slope of 0.95. The positive predictive value of patients with high scores on the model was 0.37 (0.29–0.47).ConclusionsSeveral theoretically suggested predisposing and precipitating predictors, including neuroticism and stressful life events, surprisingly failed to contribute to our final model. Moreover, this model mostly included general predictors of increased risk of repeated consultations among patients with FSS. The model discrimination and positive predictive values were insufficient and preclude clinical implementation.

Introduction There is growing evidence that mental disorders behave like complex dynamic systems. Complex dynamic systems theory states that a slower recovery from small perturbations indicates a loss of resilience of a system. This study is the first to test whether the speed of recovery of affect states from small daily life perturbations predicts changes in psychopathological symptoms over 1 year in a group of adolescents at increased risk for mental disorders. Methods We used data from 157 adolescents from the TWINSSCAN study. Course of psychopathology was operationalized as the 1-year change in the Symptom Checklist-90 sum score. Two groups were defined: one with stable and one with increasing symptom levels. Time-series data on momentary daily affect and daily unpleasant events were collected 10 times a day for 6 days at baseline. We modeled the time-lagged effect of daily unpleasant events on negative and positive affect after each unpleasant event experienced, to examine at which time point the impact of the events is no longer detectable. Results There was a significant difference between groups in the effect of unpleasant events on negative affect 90 min after the events were reported. Stratified by group, in the Increase group, the effect of unpleasant events on both negative (B = 0.05, p B = − 0. 08, p Conclusion Findings cautiously suggest that adolescents who develop more symptoms in the following year may display a slower affect recovery from daily perturbations at baseline. This supports the notion that mental health may behave according to the laws of a complex dynamic system. Future research needs to examine whether these dynamic indicators of system resilience may prove valuable for personalized risk assessment in this field.

ObjectiveThis study systematically summarizes the evidence of all observational studies investigating the relation between accumulation of adverse life events and measures of overweight in children MethodsMEDLINE, Embase, PsycINFO, and CINAHL were systematically searched (last search date 18 February 2015). The Newcastle-Ottawa Scale was used for methodological quality assessment. Study estimates were pooled using a random-effects model, and sources of heterogeneity were explored (PROSPERO registration number CRD42014014927). ResultsEighteen articles were included, containing five longitudinal (n=6,361) and fourteen cross-sectional and case-control study results (n=52,318). The pooled estimate of the longitudinal studies showed that accumulation of adverse life events is positively related to childhood overweight measures (OR [95% CI]=1.12 [1.01-1.25]). Cross-sectional and case-control study results were heterogeneous. Subgroup analyses showed that cross-sectional and case-control studies using a continuous adverse events measure, studies using a continuous overweight measure, and studies in children >6-12 years also generated positive pooled estimates, while the pooled estimate of studies assessing recent adverse events (past 2 years) was indicative of no relation with overweight. ConclusionsAccumulation of adverse life events and childhood overweight measures are positively associated. However, increases in overweight measures in response to adverse childhood events do not seem to occur instantaneously.

Background Intensive longitudinal (IL) designs provide the potential to study symptoms as they evolve in real-time within individuals. This has promising clinical implications, potentially allowing conclusions at the level of specific individuals. The current study aimed to establish the feasibility of IL designs, as indicated by self-rated burden and attrition, in the context of psychiatry. Additionally, we evaluated three core assumptions about the instruments (diary items) used in IL designs. These assumptions are: diary items (1) reflect experiences that change over time within individuals (indicated by item variability), (2) are interpreted consistently over time, and (3) correspond to retrospective assessments of psychopathology. Methods TRAILS TRANS-ID is an add-on IL study in the clinical cohort of the TRAILS study. Daily diaries on psychopathological symptoms for six consecutive months were completed by 134 at risk young adults (age 22.6 ± 0.6 years). At baseline, immediately after the diary period, and one year after the diary period, participants completed a diagnostic interview. Results Excellent compliance (88.5% of the diaries completed), low participant burden (M = 3.21; SD = 1.42; range 1–10), and low attrition (8.2%) supported the feasibility of six-month IL designs. Diary items differed in their variability over time. Evaluation of the consistency of diary item interpretations showed that within-individual variability in scores could not be attributed to changing interpretations over time. Further, daily symptom reports reasonably correlated with retrospective assessments (over a six month period) of psychopathology obtained with the diagnostic interview, suggesting that both measures might complement each other. Conclusion The current study is the first to show that IL designs over extensive periods (i.e., multiple months) in psychiatry are feasible, and meet three core assumptions to study change in psychopathology. This might allow for addressing novel and promising hypotheses in our field, and might substantially alter how we treat and study mental ill-health.

Background: The locus of control (LOC) construct has been associated with onset, course, and severity of anxiety and depression. We investigated the stability of LOC, the bidirectional relationships between LOC and symptom severity of anxiety and depression over nine years, and the influence of intermediate positive and negative life-events on these associations.Methods: Data came from five assessment waves over nine years of 2052 subjects with an anxiety or depressive disorder or healthy controls. First, the stability of LOC (assessed with 5-item Mastery Scale) was tested. Next, associations between LOC, anxiety severity (Beck Anxiety Inventory), depression severity (Inventory of Depressive Symptomatology), and intermediate positive and negative life-events (20-item List of Threatening Experience Questionnaire) were determined with structural equation modeling.Results: LOC was rather stable over nine years (r = 0.62), and scores increased slightly with age (i.e. became more internal). LOC yielded equal stability estimates as symptom levels of anxiety and depression did over nine years. A more external LOC predicted higher anxiety and depression severity, but did not influence the incidence of positive and negative life-events. Higher depression severity and more negative life-events predicted the development of a more external LOC, whereas more positive life-events predicted a more internal LOC. Anxiety severity had no effect on LOC.Limitations: Life-events were assessed with self-report measures.Conclusions: The prospective associations between LOC and meaningful changes in anxiety and depressive symptom severity and experienced life-events may yield important new insights for clinical interventions.

Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p

Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p

Supported by the European Community’s Seventh Framework Program under grant agreement No. HEALTH-F2-2009-241909 (Project EU-GEI), Schepers, E., Lousberg, R., Guloksuz, S., Pries, L.-K., Delespaul, P., Kenis, G., Luykx, J.J., Lin, B.D., Richards, A.L., Akdede, B., Binbay, T., Altınyazar, V., Yalınçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Cankurtaran, E.Ş., Kaymak, S.U., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Bernardo, M., Cabrera, B., Bobes, J., Saiz, P.A., García-Portilla, M.P., Sanjuan, J., Aguilar, E.J., Santos, J.L., Jiménez-López, E., Arrojo, M., Carracedo, A., López, G., González-Peñas, J., Parellada, M., Maric, N.P., Atbaşoğlu, C., Ucok, A., Alptekin, K., Saka, M.C., Arango, C., Rutten, B.P.F., van Os, J.

Objective: To test age- and sex-specific associations between adverse life events and functional bodily symptoms (FBS) in the general population.Methods: In a population-based cohort, 964 participants (mean age 55 years SD 11,48% male) completed two measurements waves of the present study. Lifetime exposure to 12 adverse life events was assessed through a modified version of the List of Threatening Experiences. Stress-sensitive personality was assessed with the 12-item neuroticism scale of the Eysenck Personality Questionnaire-Revised. Socio-economic status was retrieved from questionnaires. Participants completed the somatization section of the Composite International Diagnostic Interview to survey the presence of 42 FBS in the previous year.Results: Regression analyses, adjusted for age, revealed that lifetime scores of adverse life events were significantly associated with FBS in the previous year, an association that was nearly identical for females (beta = 0.18, t = 4.07, p Conclusion: Adverse life events during lifetime were associated with FBS in the previous year. This association was dependent on age and sex but largely independent of having a stress-sensitive personality or low socioeconomic status. Future studies could adopt a life course perspective to study the role of adverse life events in FBS. (C) 2015 Elsevier Inc. All rights reserved.

Background.Telomere attrition might be one of the mechanisms through which psychosocial stress leads to somatic disease. To date it is unknown if exposure to adverse life events in adulthood is associated with telomere shortening prospectively. In the current study we investigated whether life events are associated with shortening of telomere length (TL).Method.Participants were 1094 adults (mean age 53.1, range 33–79 years) from the PREVEND cohort. Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Life events were assessed with an adjusted version of the List of Threatening Events (LTE). TL was measured by monochrome multiplex quantitative PCR at T1, T2, and T3. A linear mixed model was used to assess the effect of recent life events on TL prospectively. Multivariable regression analyses were performed to assess whether the lifetime life events score or the score of life events experienced before the age of 12 predicted TL cross-sectionally. All final models were adjusted for age, sex, body mass index, presence of chronic diseases, frequency of sports, smoking status, and level of education.Results.Recent life events significantly predicted telomere attrition prospectively (B= −0.031,p= 0.007). We were not able to demonstrate a significant cross-sectional relationship between the lifetime LTE score and TL. Nor did we find exposure to adverse life events before the age of 12 to be associated with TL in adulthood.Conclusions.Exposure to recent adverse life events in adulthood is associated with telomere attrition prospectively.

Background: Stress experienced during childhood or adulthood has been associated with cardiovascular disease (CVD), but it is not clear whether associations are already prevalent on a subclinical cardiovascular level. This study investigates associations between indicators of life stress and subclinical CVD, and whether these are mediated by depression and anxiety.Methods: Subjects were 650 participants of the Netherlands Study of Depression and Anxiety, aged 20-66 years, with or without (27.5%) depressive and anxiety disorders. Life stress included childhood trauma, negative life events and recently experienced daily hassles or job strain. Subclinical CVD was measured as 1) carotid atherosclerosis (intima-media thickness and the presence of plaques) using B-mode ultrasonography, and 2) central arterial stiffness (heart rate normalized augmentation index) using calibrated radial applanation tonometry.Results: Increased central arterial stiffness was shown in sub jects who had experienced childhood trauma (per SD increase: beta = .07; p = .01), or reported recently experienced daily hassles (per SD increase: beta = .06; p = .02), negative life events (per SD increase: beta = .05; p = .03), or job strain (high versus low: beta = .09; p = .01). Associations between life stress and arterial stiffness appeared to be partly mediated by severity of depressive and anxiety symptoms. No significant associations were found for childhood life events, nor between indicators of life stress and carotid atherosclerosis.Conclusions: Childhood trauma and recent life stress were associated with increased central arterial stiffness. This suggests that life stress - partly via depression and anxiety - might enhance the development and progression of CVD. (C) 2015 Elsevier Inc. All rights reserved.

Objectives: Growing evidence indicates that inflammatory processes may play a role in the pathogenesis of anxiety disorders. Nevertheless, much remains to be learned about the involvement of inflammation, including C-reactive protein (CRP), in specific anxiety disorders. This study examines the relation between anxiety disorders and CRP. Methods: Associations of serum CRP with anxiety disorders were determined in a large population study (n = 54,326 participants, mean age = 47 years; 59% female), the LifeLines cohort. Depressive and anxiety disorders (generalized anxiety disorder, social anxiety phobia, panic disorder with or without agoraphobia and agoraphobia without panic disorder) were assessed using the Mini-International Neuropsychiatric Interview. Results: Anxiety disorders, with the exception of social anxiety disorder, were significantly associated with increased CRP. After adjusting for demographics, life style factors, health factors, medication use, depression, and psychological stressors, CRP remained significantly associated with panic disorder with agoraphobia (β = 0.01, P = .013). Moreover, CRP levels were significantly higher in people with panic disorder with agoraphobia compared to other anxiety disorders, independent of all covariates (F = 3.00, df = 4, P = .021). Conclusions: Panic disorder with agoraphobia is associated with increased CRP, although the effect size of this association is small. This indicates that neuroinflammatory mechanisms may play a potential role in its pathophysiology.

Objective Our objective was to assess whether self-reported adverse life events during childhood or over the lifespan are associated with altered activity of the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal axis (HPA axis), and the immune system. Method This study was performed in a population-based cohort of 1094 adults aged 33–79 years, 46.3% male, average age 53 (SD 11.4). Two waves of data were collected at a 2-year interval, enabling replication of the analyses. Cumulative exposure to adverse life events was assessed by means of the List of Threatening Experiences. ANS function was assessed by spectral analysis of heart rate variability in the high-frequency band (HRV-HF). HPA axis function was assessed by 24-h urinary free cortisol (24-h UFC) excretion. Inflammation was assessed by high-sensitive C-reactive protein (hsCRP). Results Multiple linear regression analyses did not reveal any significant associations, with the exception of one significant negative association between the lifetime score of adverse life events and HRV-HF β = −0.028; P = 0.037 at baseline, but not at follow up 2 years later. Conclusion In a large population-based cohort, adverse life events were not consistently associated with HRV-HF, 24-h UFC or (hsCRP).

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain.PERSPECTIVE: Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve.

Background: We examined the association of cognitive vulnerability to depression with changes in homogeneous measures of depressive symptoms.Methods: Baseline and 1-year follow-up data were obtained from 2981 participants of the Netherlands study of depression and anxiety. Multivariate regression analyses were carried out on cognitive reactivity, locus of control and implicit and explicit self-depressive associations in combination with negative life events. The purpose of this analysis was to predict changes on the mood/cognition and anxiety/arousal subscales of the inventory of depressive symptomatology - self report.Results: Cognitive reactivity, locus of control and explicit self-depressive associations were independently associated with changes in depressive symptoms after adjustment for covariates and baseline severity (all p Limitations: The study sample is over-inclusive of depressed patients. Therefore it might be problematic generalizing the findings to the general population.Conclusion: Cognitive etiological factors may play a role in a "cognitive" subtype of depression. The findings strengthen the notion that homogeneous measures of depressive symptoms enable a greater degree of discrimination between subtypes than a multidimensional conception of depression. (C) 2013 Elsevier B.V. All rights reserved

Contains fulltext : 178008.pdf (Publisher’s version ) (Open Access) OBJECTIVES: Anxious depression is associated with severe impairment and bad prognoses. We hypothesize that recent life-events are associated with more anxiety in late-life depression and that this is conditional upon the level of certain personality traits. METHOD: Baseline data of the Netherlands Study of Depression in Older Persons (NESDO) were used. In 333 patients (>/=60 years) suffering from a major depressive disorder, anxiety was assessed with the BAI, personality traits with the NEO-FFI and the Mastery Scale, and life-events with the Brugha questionnaire. Multiple linear regression analyses were applied with anxiety severity as dependent and life-events and personality traits as independent variables. RESULTS: 147 patients (44.1%) had recently experienced one or more life-events. The presence of a life-event is not associated with anxiety (p = .161) or depression severity (p = .440). However, certain personality traits interacted with life-events in explaining anxiety severity. Stratified analyses showed that life-events were associated with higher anxiety levels in case of high levels of neuroticism and openness and low levels of conscientiousness or mastery. CONCLUSIONS: In the face of a life-event, personality traits may play a central role in increased anxiety levels in late-life depression.

Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive comorbidity and "double" comorbidity (i.e. anxiety and depressive comorbidity).Methods: Data were obtained from the Netherlands Study of Anxiety and Depression (NESDA). A sample of 1004 participants with a current anxiety disorder was evaluated.Results: As compared with single anxiety, anxiety-anxiety comorbidity was associated with higher severity, greater chronicity and more treatment. Anxiety-anxiety comorbidity was associated with an earlier age of onset and a more chronic course compared with anxiety-depressive comorbidity, while anxiety-depressive comorbidity was associated with more severe symptoms and more impaired functioning than anxiety-anxiety comorbidity. "Double" comorbidity was associated with higher severity, greater chronicity, more treatment and increased disability. Sociodemographic and vulnerability factors were comparable among the four groups.LimitationsA prospective design would be more appropriate to study the outcome. In this study no distinction was made between whether depression or anxiety disorder preceded the current anxiety disorder.Conclusions: It is clinical relevant to diagnose and treat comorbidity among anxiety disorders as it is associated with higher severity and more chronicity. Whereas anxiety-anxiety comorbidity has an earlier age of onset and a more chronic course, anxiety-depressive comorbidity leads to more treatment and impaired functioning. "Double" comorbidity leads to even more severity, chronicity and impairment functioning compared with both anxiety-anxiety and anxiety-depressive comorbidity. (C) 2011 Elsevier B.V. All rights reserved.

Contains fulltext : 98431.pdf (Publisher’s version ) (Open Access) RATIONALE: Recent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover, the effects of stressful events on BDNF levels may in part be conditional upon a common variant on the BDNF gene (Val(66)Met; RS6265), with the Met allele being associated with a decrease in activity-dependent secretion of BDNF compared to the Val allele. METHODS: We investigated cross-sectionally in 1,435 individuals with lifetime MDD the impact of childhood abuse (CA) and recent life events on serum BDNF levels and assessed whether the impact of these events was moderated by the BDNF Val(66)Met polymorphism. RESULTS: Overall, BDNF Met carriers had reduced serum BDNF levels when exposed to CA in a dose-dependent way. Moreover, exposure to recent life events was also associated with decreases in BDNF levels, but this was independent of BDNF Val(66)Met. Moreover, when not exposed to CA, Met carriers had higher BDNF levels than the Val/Val individuals, who did not show decreases in BDNF associated with CA. Finally, these findings were only apparent in the MDD group without comorbid anxiety. CONCLUSIONS: These gene-environment interactions on serum BDNF levels suggest that Met carriers are particularly sensitive to (early) stressful life events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events.

Background.- Interpersonal difficulties and stressful life events are important etiological factors in (recurrence of) depression. This study examines whether stressful life events mediate the influence of problems in nonverbal communication on recurrence of depression.Methods.- We registered nonverbal expressions of involvement from videotaped behavior of 101 remitted outpatients and their interviewers. During a 2-year follow-up, We assessed stressful life events and recurrence of depression.Results.- The less congruent the levels of nonverbal involvement behavior of participants and interviewers, the higher the incidence of stressful life events, and -via these - the risk of recurrence.Limitations.- Nonverbal behavior was measured in an experimental setting.Conclusions.- The results suggest that lack of nonverbal congruence during social interaction contributes to the occurrence of stressful life events, which in turn may trigger depression. (c) 2006 Elsevier B.V All rights reserved.

Preventing recurrence of depression forms an important challenge for current treatments. Cognitive control impairments often remain present during remission of depression, putting remitted depressed patients at heightened risk for new depressive episodes by disrupting emotion regulation processes. Importantly, research indicates that cognitive control training targeting working memory functioning shows potential in reducing maladaptive emotion regulation and depressive symptomatology in clinically depressed patients and at-risk student samples. The current study aims to test the effectiveness of cognitive control training as a preventive intervention in a remitted depressed sample, exploring effects of cognitive control training on rumination and depressive symptomatology, along with indicators of adaptive emotion regulation and functioning. We present a double blind randomized controlled design. Remitted depressed adults will complete 10 online sessions of a cognitive control training targeting working memory functioning or a low cognitive load training (active control condition) over a period of 14 days. Effects of training on primary outcome measures of rumination and depressive symptomatology will be assessed pre-post training and at three months follow-up, along with secondary outcome measure adaptive emotion regulation. Long-term effects of cognitive control training on broader indicators of functioning will be assessed at three months follow-up (secondary outcome measures). This study will provide information about the effectiveness of cognitive control training for remitted depressed adults in reducing vulnerability for depression. Furthermore, this study will address key questions concerning the mechanisms underlying the effects of cognitive control training, will take into account the subjective experience of the patients (including a self-report measure for cognitive functioning), and explore whether these effects extend to broad measures of functioning such as Quality of Life and disability. This study is registered with ClinicalTrials.Gov, number NCT02407652 .

Contains fulltext : 154763.pdf (Publisher’s version ) (Closed access) One of the leading neurobiological hypotheses on depression states that decreased expression of brain-derived neurotrophic factor (BDNF) contributes to depression. This is supported by consistent findings of low serum BDNF levels in depressed patients compared with non-depressed controls. Whereas it has been generally assumed that this is a state characteristic of depression, strong inferences about state or trait effects require a longitudinal study design. To investigate the longitudinal association between serum BDNF and depression, we measured serum BDNF, (current and past) depression status, use of antidepressants, and all potential covariates at baseline and after 2 years in 1751 individuals, consisting of patients with an incident (n=153), remitted (n=420) and persistent depression (n=310) and non-depressed controls (n=868). We analyzed change/differences in serum BDNF across these four groups with analyses of covariance adjusted for covariates and baseline BDNF value, together with the effects of starting and stopping antidepressant treatment. Our analyses revealed a significant difference for the depression course groups (P=0.007). Compared with non-depressed controls, persistently depressed and remitted patients had a steeper decrease of BDNF levels over time (-1.33 (P=0.001) and -0.97 ng ml(-1) (P=0.011), respectively), whereas BDNF reductions in patients with incident depression were similar to those in healthy controls. Initiation or discontinuation of antidepressants was not associated with BDNF change (P=0.72). These findings suggest that BDNF not only contributes to depression, but that depression in turn may also contribute to low BDNF.

IntroductionCognitive–behavioural therapy for insomnia (CBT-I) leads to insomnia symptom improvements in a substantial proportion of patients. However, not everyone responds well to this treatment, and it is unclear what determines individual differences in response. The broader aim of this work is to examine to what extent response to CBT-I is due to genetic and environmental factors. The purpose of this pilot study is to examine feasibility of a design to test hypotheses focusing on an unselected sample, that is, without selection on insomnia complaints, in order to plan a larger behavioural genetics study where most participants will likely not have an insomnia disorder.Methods and analysisA two parallel-group randomised controlled trial is being conducted across three London universities. Female students (minimum age 18 years) enrolled on a psychology programme at one of the three sites were invited to participate. The target number of participants to be recruited is 240. Following baseline assessments, participants were randomly allocated to either the treatment group, where they received weekly sessions of digital CBT-I for 6 weeks, or the control group, where they completed an online puzzle each week for 6 weeks. Follow-up assessments have taken place mid-intervention (3 weeks) and end of intervention (6 weeks). A 6-month follow-up assessment will also occur. Primary outcomes will be assessed using descriptive statistics and effect size estimates for intervention effects. Secondary outcomes will be analysed using multivariate generalised estimating equation models.Ethics and disseminationThe study received ethical approval from the Research Ethics and Integrity subcommittee, Goldsmiths, University of London (application reference: EA 1305). DNA sample collection for the BioResource received ethical approval from the NRES Committee South Central—Oxford (reference number: 15/SC/0388). The results of this work shall be published in peer-reviewed journals.Trial registration numberNCT03062891; Results.

Contains fulltext : 136881.pdf (Publisher’s version ) (Closed access) Brain-Derived Neurotrophic Factor (BDNF) serum levels are abnormally low in depressed patients as compared to healthy controls and normalize with SSRI treatment. The aim of this study is to examine serum BDNF levels in late-life depression, stratified for SSRI usage, and to explore the relation between BDNF levels and specific depression characteristics as well as between BDNF levels and early and recent life stressors in late-life depression. We assessed serum BDNF levels in 259 depressed patients not using an SSRI, 99 depressed patients using an SSRI and 119 non-depressed controls (age range 60-93 years). Depressive disorders were diagnosed with the Composite International Diagnostic Interview (CIDI, version 2.1). Serum BDNF levels were significantly higher in depressed patients who used an SSRI compared to depressed patients not using SSRIs and compared to non-depressed controls, when adjusted for age, sex, life style characteristics, cognitive functioning and somatic comorbidity. Recent life-events, assessed with the List of Threatening Events-Questionnaire, were significantly associated with lower BDNF levels in non-depressed subjects only. Although a summary score of early traumatization (before the age of 16 years) was not associated with serum BDNF levels in any of the three groups, we found an interaction between a history of severe physical abuse and SSRI usage in the depressed group. Interestingly, higher serum levels of BDNF in depressed patients using SSRIs were only found in those patients without a history of severe childhood abuse and not in those with a history of severe childhood abuse.

This study investigates whether the presence of green space can attenuate negative health impacts of stressful life events. Individual-level data on health and socio-demographic characteristics were drawn from a representative two-stage sample of 4529 Dutch respondents to the second Dutch National Survey of General Practice (DNSGP-2), conducted in 2000-2002. Health measures included: (1) the number of health complaints in the last 14 days; (2) perceived mental health (measured by the GHQ-12): and (3) a single item measure of perceived general health ranging from 'excellent' to 'poor'. Percentages of green space in a 1-km and 3-km radius around the home were derived from the 2001 National Land cover Classification database (LGN4). Data were analysed using multilevel regression analysis, with GP practices as the group-level units. All analyses were controlled for age, gender, income, education level, and level of urbanity. The results show that the relationships of stressful life events with number of health complaints and perceived general health were significantly moderated by amount of green space in a 3-km radius. Respondents with a high amount of green space in a 3-km radius were less affected by experiencing a stressful life event than respondents with a low amount of green space in this radius. The same pattern was observed for perceived mental health, although it was marginally significant. The moderating effects of green space were found only for green space within 3 km, and not for green space within 1 km of residents' homes, presumably because the 3-km indicator is more affected by the presence of larger areas of green space, that are supposed to sustain deeper forms of restoration. These results support the notion that green space can provide a buffer against the negative health impact of stressful life events. (C) 2010 Elsevier Ltd. All rights reserved.

BACKGROUND: Previous studies are inconclusive on whether poor socioeconomic conditions in the neighborhood are associated with major depressive disorder. Furthermore, conceptual models that relate neighborhood conditions to depressive disorder have not been evaluated using empirical data. In this study, we investigated whether neighborhood income is associated with major depressive episodes. We evaluated three conceptual models. Conceptual model 1: The association between neighborhood income and major depressive episodes is explained by diseases, lifestyle factors, stress and social participation. Conceptual model 2: A low individual income relative to the mean income in the neighborhood is associated with major depressive episodes. Conceptual model 3: A high income of the neighborhood buffers the effect of a low individual income on major depressive disorder.METHODS: We used adult baseline data from the LifeLines Cohort Study (N = 71,058) linked with data on the participants' neighborhoods from Statistics Netherlands. The current presence of a major depressive episode was assessed using the MINI neuropsychiatric interview. The association between neighborhood income and major depressive episodes was assessed using a mixed effect logistic regression model adjusted for age, sex, marital status, education and individual (equalized) income. This regression model was sequentially adjusted for lifestyle factors, chronic diseases, stress, and social participation to evaluate conceptual model 1. To evaluate conceptual models 2 and 3, an interaction term for neighborhood income*individual income was included.RESULTS: Multivariate regression analysis showed that a low neighborhood income is associated with major depressive episodes (OR (95 % CI): 0.82 (0.73;0.93)). Adjustment for diseases, lifestyle factors, stress, and social participation attenuated this association (ORs (95 % CI): 0.90 (0.79;1.01)). Low individual income was also associated with major depressive episodes (OR (95 % CI): 0.72 (0.68;0.76)). The interaction of individual income*neighborhood income on major depressive episodes was not significant (p = 0.173).CONCLUSIONS: Living in a low-income neighborhood is associated with major depressive episodes. Our results suggest that this association is partly explained by chronic diseases, lifestyle factors, stress and poor social participation, and thereby partly confirm conceptual model 1. Our results do not support conceptual model 2 and 3.