Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration: A Coordinated Meta-Analysis of 8 Cohort Studies.

BACKGROUND: Depressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta (Aß) and phosphorylated tau (p-tau), as well as for axonal damage (neurofilament light, NfL) and astrocytic activation (glial fibrillary acidic protein, GFAP). Hypothesizing that depressive symptoms may occur along the AD process, we investigated associations between plasma biomarkers of AD with depressive symptoms in individuals without dementia. METHODS: A two-stage meta-analysis was performed on 2 clinic-based and 6 population-based cohorts (N = 7210) as part of the Netherlands Consortium of Dementia Cohorts. Plasma markers (Aß42/40, p-tau181, NfL, and GFAP) were measured using Single Molecular Array (Simoa; Quanterix) assays. Depressive symptoms were measured with validated questionnaires. We estimated the cross-sectional association of each standardized plasma marker (determinants) with standardized depressive symptoms (outcome) using linear regressions, correcting for age, sex, education, and APOE ε4 allele presence, as well as subgrouping by sex and APOE ε4 allele. Effect estimates were entered into a random-effects meta-analysis. RESULTS: Mean age of participants was 71 years. The prevalence of clinically relevant depressive symptoms ranged from 1% to 22%. None of the plasma markers were associated with depressive symptoms in the meta-analyses. However, NfL was associated with depressive symptoms only in APOE ε4 carriers (ß 0.11; 95% CI: 0.05-0.17). CONCLUSIONS: Late-life depressive symptoms did not show an association to plasma biomarkers of AD pathology. However, in APOE ε4 allele carriers, a more profound role of neurodegeneration was suggested with depressive symptoms.

Genomics Research of Lifetime Depression in the Netherlands: The BIObanks Netherlands Internet Collaboration (BIONIC) Project.

In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.

Long-term trajectories of peak expiratory flow rate in older men and women show linear decline mainly determined by baseline levels.

BACKGROUND: Peak expiratory flow rate (PEFR) predicts mortality and other negative health outcomes. However, little evidence exists on how PEFR changes with ageing and how trajectories of change differ among older people. AIMS: To identify trajectories of PEFR in older men and women, and to study characteristics associated with these trajectories. METHODS: Data from the Longitudinal Aging Study Amsterdam were used, an ongoing cohort study in a representative sample of Dutch older men and women. PEFR was assessed using the Mini-Wright peak flow meter across a 13-year follow-up in 991 men and 1107 women. Trajectories were analyzed using Latent Class Growth Analysis. RESULTS: Mean age was 72.5 (SD 8.4) in men and 72.4 (SD 8.4) in women. In men, three declining trajectories were identified, i.e. high, intermediate and low, with prevalences of 30%, 46% and 24%, respectively. In women, two declining trajectories were identified, i.e. high and low, with prevalences of 62 and 38%. All trajectories showed linear decline and differed mostly with regard to their intercept. Significant differences between trajectories with regard to baseline demographic, health and lifestyle characteristics were observed, e.g., men and women in the low PEFR trajectory were older, had more chronic diseases, and were more often smoker. DISCUSSION AND CONCLUSIONS: Trajectories in both men and women differ mainly in baseline level of PEFR and not in rate of decline over time. Therefore, one PEFR measurement might be sufficient to give an indication of the trajectory that an older adult is likely to follow.

Reciprocal associations between depressive symptoms and satisfaction with sexual life in older adults: the roles of gender and importance attached to sexuality.

OBJECTIVES: To gain insight into the longitudinal, reciprocal associations between depressive symptoms and sexual satisfaction as well as the potential moderating roles of gender and perceived importance of sexuality. METHOD: We analyzed longitudinal data from 2113 participants of the Longitudinal Ageing Study Amsterdam (LASA) with an initial age range of 54-93 years, using Generalized Estimating Equations (GEE). RESULTS: There were no significant associations between baseline depressive symptoms and change in sexual satisfaction, nor between baseline sexual satisfaction and change in depressive symptoms. Gender and perceived importance of sexuality were moderators: in men higher depression scores were associated with a decrease in sexual satisfaction, whereas in women higher depression scores were associated with an increase in sexual satisfaction. In participants for whom sexual life was important, higher depression scores were associated with a decrease in sexual satisfaction. In participants for whom sexual life was not important, higher depression scores were associated with an increase in sexual satisfaction. CONCLUSION: The associations between baseline depressive symptoms and change in sexual satisfaction as well as between baseline sexual satisfaction and change in depressive symptoms varied according to gender and importance ascribed to sexuality. Potential explanations might lie in the different roles sexual activity plays in sexual satisfaction in men and women.

How sustainable is resilience? A mixed-methods study on the COVID-19-pandemic as a challenge to resilience resources of older adults who previously recovered from depression.

OBJECTIVES: Despite expanding knowledge about the internal and external resources that contribute to resilience among individuals who have experienced depression, the long-term accessibility and protectiveness of these resources across different stressors is unknown. We investigated whether and how the resilience resources of individuals who previously recovered from late-life depression remained protective during the COVID-19 pandemic. METHODS: We used a sequential explanatory mixed methods design. Quantitative data were derived from two psychiatric case-control cohorts and included twelve repeated measures during the COVID-19 pandemic (n = 465, aged ≥ 60). Qualitative data included two sequential interviews held in 2020 (n = 25) and 2021 (n = 19). We used thematic analysis to determine the protective resources after depression and during the COVID-19 pandemic and linear mixed models to examine the effect of these resources on change in depressive symptoms during the COVID-19 pandemic. RESULTS: While resources of 'Taking agency', 'Need for rest', 'Managing thought processes' and 'Learning from depression' remained accessible and protective during the pandemic, 'Social support' and 'Engaging in activities' did not. 'Negotiating with lockdown measures', 'changing social contact' and 'changing activities' were compensating strategies. Quantitative data confirmed the protectiveness of social contact, social cohesion, sense of mastery, physical activity, staying active and entertained and not following the media. CONCLUSION: Many of the resources that previously helped to recover from depression also helped to maintain good mental health during the COVID-19 pandemic. Where accessibility and protectiveness declined, compensatory strategies or new resources were used. Hence, the sustainability of resilience is enabled through adaptation and compensation processes.

The associations between sleep quality, mood, pain and appetite in community dwelling older adults: a daily experience study.

OBJECTIVES: To investigate the daily life experiences of sleep, mood, and pain in relation to appetite in community-dwelling older adults aged 75 years and older, stratified by sex. DESIGN: Existing data from a daily experience study embedded in the Longitudinal Aging Study Amsterdam (LASA) among the oldest-old (≥75 years). SETTING: LASA is an ongoing cohort study of a nationally representative sample of older adults aged ≥55 years from three culturally distinct regions in the Netherlands. PARTICIPANTS: 434 community-dwelling older adults aged ≥75 years. MEASUREMENTS: Participants filled-out a one-week diary on daily experience of pain, mood, last night sleep (10-point Likert scale), and appetite (5-point Likert scale) on five measurement occasions between 2016 and 2021. (Hybrid) linear mixed models were used to investigate overall, within-subject and between-subject association between mood, sleep, and pain (independent variables) and appetite (dependent variable), while correcting between-subject associations for season, age, educational level, partner status, body mass index, alcohol consumption, physical activity level, smoking status, chronic diseases and use of nervous system medication, stratified by sex. RESULTS: Averaged over all days, males reported a poor appetite on 12% of the days and females on 19% of the days. Statistically significant between-subject associations with a poorer appetite were found for lower mood (unstandardized b = 0.084 [95% CI 0.043-0.126] (males), (b = 0.126 [95% CI 0.082-0.170] (females)), poorer sleep (b = 0.045 [95% CI 0.007-0.083] (males), (b = 0.51 [95% CI 0.017-0.085] (females)) and more severe pain in males only (b = 0.026 [95% CI 0.002-0.051]). Except for pain, within-subject associations were somewhat weaker: mood: b = 0.038 [95% CI 0.016-0.060] (males), (b = 0.082 [95% CI 0.061-0.104] (females)); sleep: b = 0.029 [95% CI 0.008-0.050] (males), (b = 0.15 [95% CI 0.005-0.025] (females)); and pain (b = 0.032 [95% CI 0.004-0.059] (males)). CONCLUSIONS: This study found that poor sleep, low mood (more strongly in females) and more severe pain (males only) are associated with poor appetite in older adults on a daily level both within and between persons. Sex differences in factors related to poor appetite should be considered in future research.

Bipolarity in Older individuals Living without Drugs (BOLD): Protocol and preliminary findings.

INTRODUCTION: Although clinical guidelines regard prophylactic medication as the cornerstone of treatment, it is estimated almost half of patients with bipolar disorder (BD) live without medication. This group is underrepresented in research but can provide indispensable knowledge on natural course, resilience and self-management strategies. We aim to describe the clinical phenotype of patients diagnosed with BD who have discontinued maintenance treatment. METHODS: The mixed-methods BOLD study included 58 individuals aged 50 years and over with BD that did not use maintenance medication in the past 5 years. A preliminary, quantitative comparison of clinical characteristics between BOLD and our pre-existing cohort of >220 older BD outpatients with medication (Dutch Older Bipolars, DOBi) was performed. RESULTS: BD-I, psychiatric comorbidities, number of mood episodes and lifetime psychotic features were more prevalent in BOLD compared to DOBi. BOLD participants had a younger age at onset and reported more childhood trauma. BOLD participants reported fewer current mood symptoms and higher cognitive, social, and global functioning. LIMITATIONS: Our findings may not be generalizable to all individuals diagnosed with BD living without maintenance medication due to selection-bias. CONCLUSION: A group of individuals exists that meets diagnostic criteria of BD and is living without maintenance medication. They appear to be relatively successful in terms of psychosocial functioning, although they do not have a milder clinical course than those on maintenance medication. The high prevalence of childhood trauma warrants further investigation. Future analyses will examine differences between BOLD and DOBi per domain (e.g. cognition, physical health, psychosocial functioning, coping).