"I Should've Been Able to Decide for Myself, but I Didn't Want to Be Left Alone." A Qualitative Interview Study of Clients' Ethical Challenges and Norms Regarding Decision-Making in Gender-Affirming Medical Care.

This qualitative study aimed to map and provide insight into the ethical challenges and norms of adult transgender and gender diverse (TGD) clients in gender-affirming medical care (GAMC). By doing so, we seek to make an empirical and constructive contribution to the dialogue on and moral inquiry into what good decision-making in GAMC should entail. We conducted 10 semi-structured interviews with adult Dutch TGD people who received GAMC. In our thematic analysis, we (1) included both ethical challenges and norms, (2) differentiated between explicit and implicit ethical challenges and norms, and (3) ascertained the specific context in which the latter emerged. We identified the following themes: (1) clients should be in the lead, (2) harm should be prevented, and (3) the decision-making process should be attuned to the individual client. These themes arose in the context of (1) a precarious client-clinician relationship and (2) distinct characteristics of GAMC. Our findings highlight divergent and dynamic decisional challenges and normative views-both within individual clients and among them. We conclude that there is no single ideal model of good decision-making in GAMC and argue that elucidating and jointly deliberating on decisional norms and challenges should be an inherent part of co-constructing good decision-making.

Doing and undoing transgender health care: The ordering of 'gender dysphoria' in clinical practice.

A formal Gender Dysphoria classification- as outlined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders- is a prerequisite for the reimbursement of both gender-affirming medical care and transgender mental health care in the Netherlands. Gender Dysphoria and its conceptual precursors have always been moving targets: moving due to research, policy, care practices and activism both within and outside of medicine. This raises the question of what Gender Dysphoria is exactly. To elucidate this question, we turn to the people who use the concept in clinical practice to come to a diagnosis and treatment indication: mental health professionals working in gender-affirming medical care and transgender mental health care. Using a material semiotics approach, we reflect upon how Gender Dysphoria is done in clinical practice. Based on an analysis of seventeen practice-based interviews with clinicians as well as an examination of clinical guidelines and texts, we describe four modes in which Gender Dysphoria is ordered. These modes of ordering illustrate that Gender Dysphoria is not one, but multiple. We illustrate how in the mode of isolating, Gender Dysphoria is something which is carefully isolated from mental disorders, while in the modes doing the future and narrating, Gender Dysphoria is done as a continuous and predictable object of care. Such orderings of Gender Dysphoria potentially conflict with a fourth mode of ordering: the doing of diversity in transgender health care. The study's findings provide empirical insights into how transgender health care is currently done in The Netherlands and provide a foundation on which ethical debates on what good transgender health care should entail.

GenderJourney: Participatory development of an ethics support tool to foster dialogue and reflection on shared decision-making in gender-affirming medical care.

OBJECTIVE: To describe and reflect on the development process of GenderJourney: an ethics support tool that seeks to foster (dialogue and reflection on) shared decision-making (SDM) in gender-affirming medical care (GAMC). METHODS: Part of a larger project, this study used a participatory design. We included transgender and gender diverse (TGD) clients and healthcare professionals (HCPs) throughout the study in co-creation workshops. In an iterative process, we (1) established stakeholders' needs, (2) reached a consensus on the aims, content, and design, (3) developed and tested successive renditions, and (4) presented the final version of the tool. RESULTS: The final tool aims to (A) elucidate the client's care request and corresponding treatment preferences, (B) foster an explicit dialogue between TGD client and HCP about expected/preferred decisional roles and collaboration, (C) stimulate a systematic joint reflection on and handling of SDM-related ethical challenges. CONCLUSION: The GenderJourney provides non-directive ethics support to jointly reflect on and foster good SDM, including its inherent ethical challenges. Future studies should focus on its implementation and actual contribution to good SDM. PRACTICE IMPLICATIONS: GenderJourney may be used in GAMC to support the dialogue on what good SDM entails and the identification, discussion, and handling of SDM-related ethical challenges.

Sociodemographic, lifestyle and clinical characteristics of energy-related depression symptoms: A pooled analysis of 13,965 depressed cases in 8 Dutch cohorts.

BACKGROUND: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.g. increased BMI and inflammatory markers). This clustering is proposed to reflect a more homogeneous depression pathology. This study examines to what extent energy-related symptoms are associated and share sociodemographic, lifestyle and clinical characteristics. METHODS: Data were available from 13,965 participants from eight Dutch cohorts with DSM-5 lifetime major depression assessed by the Lifetime Depression Assessment Self-report (LIDAS) questionnaire. Information on four energy-related depression symptoms were extracted: energy loss, increased appetite, increased weight, and hypersomnia. Tetrachoric correlations between these symptoms, and associations of these symptoms with sociodemographic (sex, age, education), lifestyle (physical activity, BMI, smoking) and clinical characteristics (age of onset, episode duration, history, treatment and recency, and self-reported comorbidity) were computed. RESULTS: Correlations between energy-related symptoms were overall higher than those with other depression symptoms and varied from 0.90 (increased appetite vs increased weight) to 0.11 (increased appetite vs energy loss). All energy-related symptoms were strongly associated with higher BMI and a more severe clinical profile. Patients with increased appetite were more often smokers, and only patients with increased appetite or weight more often had a self-reported diagnosis of PTSD (OR = 1.17, p = 2.91E-08) and eating disorder (OR = 1.40, p = 4.08E-17). CONCLUSIONS: The symptom-specific associations may have consequences for a profile integrating these symptoms, which can be used to reflect immuno-metabolic depression. They indicate the need to study immuno-metabolic depression at individual symptom resolution as a starting point.

Sharing decisions amid uncertainties: a qualitative interview study of healthcare professionals' ethical challenges and norms regarding decision-making in gender-affirming medical care.

BACKGROUND: In gender-affirming medical care (GAMC), ethical challenges in decision-making are ubiquitous. These challenges are becoming more pressing due to exponentially increasing referrals, politico-legal contestation, and divergent normative views regarding decisional roles and models. Little is known, however, about what ethical challenges related to decision-making healthcare professionals (HCPs) themselves face in their daily work in GAMC and how these relate to, for example, the subjective nature of Gender Incongruence (GI), the multidisciplinary character of GAMC and the role HCPs play in assessing GI and eligibility for interventions. Given the relevance and urgency of these questions, we conducted a qualitative study among HCPs providing GAMC to transgender adults in the Netherlands. METHODS: In this qualitative research, we conducted 11 semi-structured interviews between May 2020 and February 2021 with HCPs (six mental health professionals, two HCPs in endocrinology, two in plastic surgery, and one in nursing) working in two distinct GAMC settings. We purposively sampled for professional background and years of experience in GAMC. We analyzed our interview data using thematic analysis. As some respondents were more inclined to speak about what should or ought to be done to arrive at good or right decision-making, we identified both ethical challenges and norms. Furthermore, in our analysis, we differentiated between respondents' explicit and implicit ethical challenges and norms and ascertained the specific context in which these challenges emerged. RESULTS: Respondents' ethical challenges and norms centered on (1) dividing and defining decisional roles and bounds, (2) negotiating decision-making in a (multidisciplinary) team, and (3) navigating various decision-making temporalities. These themes arose in the context of uncertainties regarding (1) GAMC's guidelines, evidence, and outcomes, as well as (2) the boundaries and assessment of GI. CONCLUSIONS: This interview study provides detailed empirical insight into both the explicit and implicit ethical challenges that HCPs experience and their ethical norms regarding decision-making. It also describes how uncertainties and (implicit) normativities concerning GAMC and GI pre-structure the moral environment in which these challenges and norms manifest. We provide normative reflections and recommendations on handling these ethical challenges in a way that is sensitive to the context in which they arise.

Symptoms of depression and insomnia in older age: A within-individual analysis over 20 years.

BACKGROUND: Depression and insomnia often co-occur, and precede one another. Possibly, insomnia gives rise to depression, and vice versa. We tested whether insomnia symptoms of an older individual are associated with later depressive symptoms in that older individual, and vice versa. METHODS: We performed a longitudinal analysis of data from a prospective cohort study in a large sample of community-dwelling older people (N = 3081), with measurements every three years, over a time period of 20 years. The within-individual longitudinal reciprocal relationship between symptoms of depression (Center for Epidemiological Studies Depression Scale), and symptoms of insomnia (three-item questionnaire, including difficulty initiating sleep, nightly awakenings, and early morning awakening) was modeled by means of a bivariate linear growth model. We tested whether symptoms of insomnia were associated with symptoms of depression three years later, and vice versa. RESULTS: Severity of symptoms of depression and insomnia and their within-individual average change over time were moderately correlated (correlation of intercepts: rho 0.41, 95% CI: 0.36 to 0.46 p < 0.001; correlation of slopes: rho 0.39, 95% CI: 0.25 to 0.52, p < 0.001). Symptoms of depression were not found to be associated with an additional risk of higher symptoms of insomnia three years later, and vice versa (p = 0.329 and p = 0.919, respectively). Similar results were found when analyses were corrected for covariates. CONCLUSIONS: In older individuals, depression and insomnia are associated and tend to increase concurrently over time, but constitute no additional risk for one another over repeated three-year intervals. These findings contradict previous research that suggests that depression and insomnia are risk factors for one another over time. The current study stands out due to the longitudinal within-individual statistical approach, but is limited by the three-year interval between measures.

Insulin resistance as a marker for the immune-metabolic subtype of depression.

OBJECTIVE: Insulin resistance (IR), a marker of metabolic dysregulation and pro-inflammatory state, moderates the antidepressant treatment effect in patients with type 2 diabetes (T2D) and is therefore a potential marker for personalized treatment. Based on data from a light therapy trial (NTR4942), we aimed to evaluate whether 1) depression symptoms differ according to the level of IR, and 2) improvement of specific depression symptoms drive the positive effects of light therapy in those with higher IR. METHODS: This secondary analysis in 59 individuals with depression and T2D explored differences in depressive symptom profile (30-item Inventory of Depressive Symptomatology (IDS)) at baseline and in response to light therapy (versus placebo), between lower and higher IR individuals, using Likelihood Ratio tests and Linear-by-linear association. IR was measured using the gold standard, a hyperinsulinemic-euglycaemic clamp. RESULTS: At baseline, higher IR individuals reported more symptoms of irritability (p=0.024) anhedonia (no interest in people and activities: p=0.011; absence of pleasure and enjoyment: p=0.021), fatigue (fatigue: p=0.036; physical fatigue: p=0.035) and hypersomnia (p=0.029) relative to persons with lower IR, who reported more insomnia (nightly awakening: p=0.041; early morning awakening: p=0.012). Light therapy led to an improvement across IDS symptoms in higher IR individuals, while in lower IR individuals, light therapy improved early morning awakening (p=0.005) and interest in people and activities (p=0.015), but worsened mood (feeling sad: p=0.001; feeling irritable: p=0.002; interpersonal sensitivity: p=0.014). CONCLUSIONS: Results add to the hypothesis of an immune-metabolic subtype of depression, and suggest that IR might be a promising focus for precision medicine.

Decision-making approaches in transgender healthcare: conceptual analysis and ethical implications.

Over the past decades, great strides have been made to professionalize and increase access to transgender medicine. As the (biomedical) evidence base grows and conceptualizations regarding gender dysphoria/gender incongruence evolve, so too do ideas regarding what constitutes good treatment and decision-making in transgender healthcare. Against this background, differing care models arose, including the 'Standards of Care' and the so-called 'Informed Consent Model'. In these care models, ethical notions and principles such as 'decision-making' and 'autonomy' are often referred to, but left unsubstantiated. This not only transpires into the consultation room where stakeholders are confronted with many different ethical challenges in decision-making, but also hampers a more explicit discussion of what good decision-making in transgender medicine should be comprised of. The aim of this paper is to make explicit the conceptual and normative assumptions regarding decision-making and client autonomy underpinning the 'Standards of Care' and 'Informed Consent Model' currently used in transgender care. Furthermore, we illustrate how this elucidation aids in better understanding stakeholders' ethical challenges related to decision-making. Our ethical analysis lays bare how distinct normative ambiguities in both care models influence decision-making in practice and how foregrounding one normative model for decision-making is no moral panacea. We suggest that the first steps towards good decision-making in gender-affirming medical care are the acknowledgement of its inherent normative and moral dimensions and a shared, dialogical approach towards the decision-making process.

Measurement and genetic architecture of lifetime depression in the Netherlands as assessed by LIDAS (Lifetime Depression Assessment Self-report).

BACKGROUND: Major depressive disorder (MDD) is a common mood disorder, with a heritability of around 34%. Molecular genetic studies made significant progress and identified genetic markers associated with the risk of MDD; however, progress is slowed down by substantial heterogeneity as MDD is assessed differently across international cohorts. Here, we used a standardized online approach to measure MDD in multiple cohorts in the Netherlands and evaluated whether this approach can be used in epidemiological and genetic association studies of depression. METHODS: Within the Biobank Netherlands Internet Collaboration (BIONIC) project, we collected MDD data in eight cohorts involving 31 936 participants, using the online Lifetime Depression Assessment Self-report (LIDAS), and estimated the prevalence of current and lifetime MDD in 22 623 unrelated individuals. In a large Netherlands Twin Register (NTR) twin-family dataset (n ≈ 18 000), we estimated the heritability of MDD, and the prediction of MDD in a subset (n = 4782) through Polygenic Risk Score (PRS). RESULTS: Estimates of current and lifetime MDD prevalence were 6.7% and 18.1%, respectively, in line with population estimates based on validated psychiatric interviews. In the NTR heritability estimates were 0.34/0.30 (s.e. = 0.02/0.02) for current/lifetime MDD, respectively, showing that the LIDAS gives similar heritability rates for MDD as reported in the literature. The PRS predicted risk of MDD (OR 1.23, 95% CI 1.15-1.32, R2 = 1.47%). CONCLUSIONS: By assessing MDD status in the Netherlands using the LIDAS instrument, we were able to confirm previously reported MDD prevalence and heritability estimates, which suggests that this instrument can be used in epidemiological and genetic association studies of depression.

Prevalence of Insomnia (Symptoms) in T2D and Association With Metabolic Parameters and Glycemic Control: Meta-Analysis.

OBJECTIVE: We aimed to determine the prevalence of insomnia and insomnia symptoms and its association with metabolic parameters and glycemic control in people with type 2 diabetes (T2D) in a systematic review and meta-analysis. DATA SOURCES: A systematic literature search was conducted in PubMed/Embase until March 2018. STUDY SELECTION: Included studies described prevalence of insomnia or insomnia symptoms and/or its association with metabolic parameters or glycemic control in adults with T2D. DATA EXTRACTION: Data extraction was performed independently by 2 reviewers, on a standardized, prepiloted form. An adaptation of Quality Assessment Tool for Quantitative Studies was used to assess the methodological quality of the included studies. DATA SYNTHESIS: When possible, results were meta-analyzed using random-effects analysis and rated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: A total of 11 329 titles/abstracts were screened and 224 were read full text in duplicate, of which 78 studies were included. The pooled prevalence of insomnia (symptoms) in people with T2D was 39% (95% confidence interval, 34-44) with I2 statistic of 100% (P < 0.00001), with a very low GRADE of evidence. Sensitivity analyses identified no clear sources of heterogeneity. Meta-analyses showed that in people with T2D, insomnia (symptoms) were associated with higher hemoglobin A1c levels (mean difference, 0.23% [0.1-0.4]) and higher fasting glucose levels (mean difference, 0.40 mmol/L [0.2-0.7]), with a low GRADE of evidence. The relative low methodological quality and high heterogeneity of the studies included in this meta-analysis complicate the interpretation of our results. CONCLUSIONS: The prevalence of insomnia (symptoms) is 39% (95% confidence interval, 34-44) in the T2D population and may be associated with deleterious glycemic control.

Sleep and HbA1c in Patients With Type 2 Diabetes: Which Sleep Characteristics Matter Most?

OBJECTIVE: Poor sleep has been identified as a risk factor for poor glycemic control in individuals with type 2 diabetes (T2D). As optimal sleep can be characterized in several ways, we evaluated which sleep characteristics are most strongly associated with glycated hemoglobin A1c (HbA1c). RESEARCH DESIGN AND METHODS: A total of 172 patients with T2D completed 7-day wrist-actigraphy and sleep questionnaires. Linear regression was used to evaluate associations between sleep measures (total sleep duration, variability in sleep duration, midsleep time, variability in midsleep time, sleep efficiency, subjective sleep quality, and subjective insomnia symptoms) and HbA1c, individually and in concert. RESULTS: Variability in sleep duration was individually most strongly associated with HbA1c (ß = 0.239; P = 0.002; R 2 = 4.9%), followed by total sleep duration (U-shaped: ß = 1.161/ß2 = 1.044; P = 0.017/0.032; R 2 = 4.3%), subjective sleep quality (ß = 0.191; P = 0.012; R 2 = 3.6%), variability in midsleep time (ß = 0.184; P = 0.016; R 2 = 3.4%), and sleep efficiency (ß = -0.150; R 2 = 2.3%). Midsleep time and subjective insomnia symptoms were not associated with HbA1c. In combination, variability in sleep duration, total sleep duration, and subjective sleep quality were significantly associated with HbA1c, together explaining 10.3% of the variance in HbA1c. Analyses adjusted for covariates provided similar results, although the strength of associations was generally decreased and showing total sleep duration and subjective sleep quality to be most strongly associated with HbA1c, together explaining 6.0% of the variance in HbA1c. CONCLUSIONS: Sleep in general may be a modifiable factor of importance for patients with T2D. The prevention of sleep curtailment may serve as a primary focus in the sleep-centered management of T2D.

Effects of Light Therapy on Mood and Insulin Sensitivity in Patients With Type 2 Diabetes and Depression: Results From a Randomized Placebo-Controlled Trial.

OBJECTIVE: Depression is common in patients with type 2 diabetes and adversely affects quality of life and diabetes outcomes. We assessed whether light therapy, an antidepressant, improves mood and insulin sensitivity in patients with depression and type 2 diabetes. RESEARCH DESIGN AND METHODS: This randomized, double-blind, placebo-controlled trial included 83 patients with depression and type 2 diabetes. The intervention comprised 4 weeks of light therapy (10,000 lux) or placebo light therapy daily at home. Primary outcomes included depressive symptoms (Inventory of Depressive Symptomatology [IDS]) and insulin sensitivity (M-value derived from the results of a hyperinsulinemic-euglycemic clamp). Secondary outcomes were related psychological and glucometabolic measures. RESULTS: Intention-to-treat analysis showed that light therapy was not superior to placebo in reducing depressive symptoms (-3.9 IDS points [95% CI -9.0 to 1.2]; P = 0.248) and had no effect on insulin sensitivity (0.15 mg/kg*min [95% CI -0.41 to 0.70]; P = 0.608). Analyses incorporating only those participants who accurately adhered to the light therapy protocol (n = 51) provided similar results, but did suggest positive effects of light therapy on depression response rates (≥50% reduction in IDS points) (26% more response; P = 0.031). Prespecified analysis showed effect moderation by baseline insulin sensitivity (P = 0.009) and use of glucose-lowering medication (P = 0.023). Light therapy did not affect depressive symptoms in participants with higher insulin sensitivity or those who use only oral glucose-lowering medication or none at all, but it did produce a relevant effect in participants with lower insulin sensitivity (-12.9 IDS points [95% CI -21.6 to -4.2]; P = 0.017) and a trend toward effectiveness in those using insulin (-12.2 IDS points [95% CI -21.3 to -3.1]; P = 0.094). Light therapy was well tolerated. CONCLUSIONS: Although this trial is essentially inconclusive, secondary analyses indicate that light therapy might be a promising treatment for depression among a subgroup of highly insulin-resistant individuals with type 2 diabetes.

Gait Speed and Processing Speed as Clinical Markers for Geriatric Health Outcomes.

OBJECTIVE: This study investigates the independent and combined potential of slowed gait speed and slowed processing speed as predictors of adverse health outcomes. The role of depressive symptoms in these associations is also investigated. METHODS: In the prospective cohort study, using the Longitudinal Aging Study Amsterdam database, three study samples for each outcome variable were defined: persistent cognitive decline (PCD; N = 1,271, 13 years of follow-up), falls (N = 1,282, 6 years of follow-up), and mortality (N = 1,559, age 74.9 ± 5.8, 21 years of follow-up). At baseline, gait speed (6-m walk with a turn at 3 m), processing speed (coding task), depressive symptoms (Center for Epidemiologic Studies Depression Scale), and basic demographic data were assessed. Also, time to PCD, falls, and mortality were assessed. Cox (for PCD and mortality) and stratified Cox (for falls) regression models were used. RESULTS: Slowed processing speed predicted PCD (HR: 7.8; 95% CI: 3.3-18.8), slowed gait speed predicted falls (HR: 1.3; 95% CI: 1.0-1.5), and both measures predicted mortality (gait speed HR: 2.1; 95% CI: 1.6-2.6; processing speed HR: 1.9; 95% CI: 1.6-2.4). Each association remained significant after adjusting for the other slowing symptom. Slowed processing speed only predicted falls in the presence of slowed gait (interaction). A slowing sum score that combines both slowing symptoms predicted all three outcomes. The associations were not influenced by depressive symptoms. CONCLUSION: Slowing of thought is as relevant as slowing of movement to predict adverse health outcomes, because they seem to represent separate underlying pathologies.

Gait Speed and the Natural Course of Depressive Symptoms in Late Life; An Independent Association With Chronicity?

INTRODUCTION: Psychomotor slowing is a core feature of depression in late life, but its prognostic value with respect to course and chronicity is unclear. We investigated whether gait speed can predict chronicity of depressive symptoms. Furthermore, we tested whether (1) cognitive slowing and (risk factors for) vascular diseases, (2) a marker of chronic inflammation, and (3) specific somatic conditions could explain this association. METHODS: In the population-based Longitudinal Aging Study Amsterdam, 271 aged participants with clinically relevant depressive symptoms (Center for Epidemiologic Studies Depression Scale ≥16) were followed during a period of 6 years. With 14 successive Center for Epidemiologic Studies Depression Scale observations, 3 clinical course types of depressive symptoms were defined. RESULTS: Remission, fluctuating course, and chronic course of depressive symptoms were seen in 21%, 48%, and 30%, respectively. Slowed gait speed at baseline was associated with a chronic course of depressive symptoms using remission as the reference (odds ratio 0.56, 95% confidence interval 0.41-0.77). Processing speed and vascular risk factors explained this association only for 2%. Specific somatic comorbidity (number of chronic diseases, chronic obstructive pulmonary disease, osteoarthritis) or inflammation influenced the odds ratio. LIMITATION: Some variables were not measured with as much detail as would be possible in a clinical study setting. CONCLUSIONS: Slowed gait speed is a robust predictor of chronicity of depressive symptoms in late life, independent of somatic comorbidity and partly in concert with a slowed processing speed. Results suggest that slowed gait speed is an integral part of the depressive syndrome, probably a subtype associated with chronic course, independent of somatic comorbidity.

Light therapy for better mood and insulin sensitivity in patients with major depression and type 2 diabetes: a randomised, double-blind, parallel-arm trial.

BACKGROUND: Major depression and type 2 diabetes often co-occur. Novel treatment strategies for depression in type 2 diabetes patients are warranted, as depression in type 2 diabetes patients is associated with poor prognosis and treatment results. Major depression and concurrent sleep disorders have been related to disturbances of the biological clock. The biological clock is also involved in regulation of glucose metabolism by modulating peripheral insulin sensitivity. Light therapy has been shown to be an effective antidepressant that 'resets' the biological clock. We here describe the protocol of a study that evaluates the hypothesis that light therapy improves mood as well as insulin sensitivity in patients with a major depressive episode and type 2 diabetes. METHODS/DESIGN: This study is a randomised, double-blind, parallel-arm trial in 98 participants with type 2 diabetes and a major depressive episode, according to DSM-IV criteria. We will assess whether light therapy improves depressive symptoms and insulin sensitivity, our primary outcome measures, and additionally investigate whether these effects are mediated by restoration of the circadian rhythmicity, as measured by sleep and hypothalamic-pituitary-adrenal axis activity. Participants will be randomly allocated to a bright white-yellowish light condition or dim green light condition. Participants will undergo light therapy for half an hour every morning for 4 weeks at home. At several time points, namely before the start of light therapy, during light therapy, after completion of 4 weeks of light therapy and after 4 weeks follow-up, several psychometrical, psychophysiological and glucometabolic measures will be performed. DISCUSSION: If light therapy effectively improves mood and insulin sensitivity in type 2 diabetes patients with a major depressive episode, light therapy may be a valuable patient friendly addition to the currently available treatment strategies. Additionally, if our data support the role of restoration of circadian rhythmicity, such an observation may guide further development of chronobiological treatment strategies in this patient population. TRIAL REGISTRATION: The Netherlands Trial Register (NTR) NTR4942 . Registered 13 January 2015.

Constructs of depression and distress in diabetes: time for an appraisal.

Depression presents in roughly 20% of people with diabetes worldwide, and adversely affects quality of life and treatment outcomes. The causes of depression in diabetes are poorly understood, but research suggests a bi-directional association, at least for type 2 diabetes. Inconsistent findings regarding prevalence and depression treatment outcomes in patients with diabetes seem partly attributable to inconsistencies in the definition and measurement of depression and in distinguishing it from diabetes-distress, a psychological concept related to depression. We review evidence suggesting that diabetes-distress and depression are correlated and overlapping constructs, but are not interchangeable. Importantly, diabetes-distress seems to mediate the association between depression and glycaemic control. We propose a model to explain the direct and indirect effects of depression and diabetes-distress on glycaemic control. Additionally, using emerging insights from data-driven approaches, we suggest three distinct symptom profiles to define depression in patients with diabetes that could help explain differential associations between depression and metabolic abnormalities, and to tailor interventions for depression. Future research should focus on further refining depression profiles in patients with diabetes, taking into account the natural history of diabetes and depression, clinical characteristics, and diabetes-distress. The assessment of diabetes-distress and depression in research and clinical practice will be essential to identify high-risk patients with different mental health needs.

A 13-year prospective cohort study on the effects of aging and frailty on the depression-pain relationship in older adults.

OBJECTIVES: The primary aim of the study is to investigate the effect of age and aging on the association between pain and depression over 13 years. We hypothesized that (1) this association would become stronger with age and frailty and that (2) this association is mainly driven by somatic and psychological factors. METHODS: Data were derived from the Longitudinal Aging Study Amsterdam, a prospective population-based cohort study with four follow-up measurements over 13 years, consisting of 1528 respondents (mean age 67.9 ± 8.1). Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale; pain was measured with an adapted version of the Nottingham Health Profile. Follow-up time and age were used as proxy variables for aging and gait speed as frailty marker. Cognition, mastery and neuroticism were measured using the mini mental state examination, the Pearlin Mastery Scale and the Dutch Personality Questionnaire respectively. RESULTS: Linear mixed models showed that pain and depressive symptoms were associated over the 13-year follow-up: b = 0.095, p < 0.001. Neither aging nor frailty changed this association. Measured somatic and psychological characteristics explained 40% of the covariance between pain and depressive symptoms over time. DISCUSSION: When dealing with people suffering from pain and depression, interventions should be similar for all aged people, encompassing both somatic and psychological factors, irrespective of age or frailty status.

Depression in context of low neuroticism is a risk factor for stroke: a 9-year cohort study.

OBJECTIVE: Depression predicts stroke; however, meta-analyses show significant heterogeneity. We hypothesize that the risk of depression on incident stroke is conditional upon the relative contribution of vascular disease and of neuroticism in the underlying pathways to depression in a specific patient. We examined whether depression increases stroke in persons with low neuroticism and without preexisting cardiac disease. METHODS: This was a population-based cohort study with 9-year follow-up (n = 2,050; ≥55 years, 52% female). The incidence of stroke was determined by self-report data as well as data from general practitioners and death certificates. Neuroticism was measured using the Dutch Personality Questionnaire and depression using the Center for Epidemiologic Studies-Depression scale. All data were analysed by Cox proportional hazards regression. RESULTS: A total of 117 incident cases of stroke occurred during follow-up. Among persons with a history of cardiac disease (n = 401), depression predicted incident stroke independent of neuroticism level with a hazard ratio (HR) of 1.05 (95% confidence interval [CI] 1.01-1.10) (p = 0.02). In persons without cardiac disease (n = 1,649), depression and neuroticism interacted significantly in predicting incident stroke (p = 0.028). Stratified analyses showed that depression predicted incident stroke in those with low neuroticism, HR 1.05 (95% CI 1.00-1.09) (p = 0.033), but not in those with high neuroticism, HR 1.01 (95% CI 0.96-1.05) (p = 0.82). CONCLUSIONS: In persons without preexistent cardiac disease, depression is only predictive for future stroke in absence of high neuroticism. This might be explained by the hypothesis that late-life depression in context of low neuroticism is a marker of subclinical vascular disease.

Is social jetlag associated with an adverse endocrine, behavioral, and cardiovascular risk profile?

Social jetlag represents the discrepancy between circadian and social clocks, which is measured as the difference in hours in midpoint of sleep between work days and free days. Previous studies have shown social jetlag to be associated with body mass index (BMI), glycated hemoglobin levels, heart rate, depressive symptoms, smoking, mental distress and alcohol use. The objective of our current study was to investigate, in a group of 145 apparently healthy participants (67 men and 78 women, aged 18-55 years, BMI 18-35 kg/m(2)), the prevalence of social jetlag and its association with adverse endocrine, behavioral and cardiovascular risk profiles as measured in vivo. participants with ≥2 h social jetlag had higher 5-h cortisol levels, slept less during the week, were more often physically inactive and had an increased resting heart rate, compared with participants who had ≤1 h social jetlag. We therefore concluded that social jetlag is associated with an adverse endocrine, behavioral and cardiovascular risk profile in apparently healthy participants. These adverse profiles put healthy participants at risk for development of metabolic diseases and mental disorders, including diabetes and depression, in the near future.

Do depressive symptoms and gait speed impairment predict each other's incidence? A 16-year prospective study in the community.

OBJECTIVES: To investigate whether gait speed predicts incident depressive symptoms and whether depressive symptoms predict incident gait speed impairment; to ascertain the presence of shared risk factors for these associations. DESIGN: The Longitudinal Aging Study Amsterdam, a prospective cohort study with five follow-up cycles over 16 years. SETTING: Population based. PARTICIPANTS: One thousand nine hundred twenty-eight respondents for incident depressive symptoms (mean age 68.9 ± 8.5) and 1,855 respondents for incident gait speed impairment (mean age 68.0 ± 8.2). MEASUREMENTS: Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale; gait speed was measured, back and forth, during a 3-m walk as quickly as possible, with a 180° turn. Multivariate analyses were performed for both sexes using Cox regression. RESULTS: Incident depressive symptoms occurred in 24% of respondents. In univariate analyses, gait speed at baseline predicted incident depressive symptoms in men and women; after adjustment for covariates, this association persisted in men only. Examining the reverse association, 34% of respondents developed gait speed impairment. Depressive symptoms at baseline were univariately associated with incident gait speed impairment in women but not in men; this association did not persist after adjustment. The bidirectional associations did not share the same explanatory variables. CONCLUSION: Gait speed predicts depressive symptoms in men. The geriatric giants of depressive symptoms and slowed gait speed in late life appear to result from different pathologies, both of which therefore require their own treatment strategies.