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.

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.

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.

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.

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.

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.

"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.

The role of immuno-metabolic depression features in the effects of light therapy in patients with depression and type 2 diabetes mellitus: A randomized controlled trial.

OBJECTIVE: Immuno-metabolic depression (IMD) is proposed to be a form of depression encompassing atypical, energy-related symptoms (AES), low-grade inflammation and metabolic dysregulations. Light therapy may alleviate AES by modulating inflammatory and metabolic pathways. We investigated whether light therapy improves clinical and biological IMD features and whether effects of light therapy on AES or depressive symptom severity are moderated by baseline IMD features. Associations between changes in symptoms and biomarkers were explored. METHODS: In secondary analyses, clinical trial data was used from 77 individuals with depression and type 2 diabetes mellitus (T2DM) randomized to four weeks of light therapy or placebo. AES severity and depressive symptom severity were based on the Inventory of Depressive Symptomatology. Biomarkers included 73 metabolites (Nightingale) summarized in three principal components and CRP, IL-6, TNF-α, INF-γ. Linear regression analyses were performed. RESULTS: Light therapy had no effect on AES severity, inflammatory markers and metabolite principle components versus placebo. None of these baseline features moderated the effects of light therapy on AES severity. Only a principle component reflecting metabolites implicated in glucose homeostasis moderated the effects of light therapy on depressive symptom severity (ßinteraction = 0.65, P = 0.001, FDR = 0.003). Changes in AES were not associated with changes in biomarkers. CONCLUSION: Findings do not support the efficacy of light therapy in reducing IMD features in patients with depression and T2DM. We find limited evidence that light therapy is a more beneficial depression treatment among those with more IMD features. Changes in clinical and biological IMD features did not align over four-weeks' time. TRIAL REGISTRATION: The Netherlands Trial Register (NTR) NTR4942.

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.

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.

Cognitive functioning and the natural course of depressive symptoms in late life.

OBJECTIVES: To investigate whether specific domains of cognitive functioning predict the natural course of depressive symptoms in older people. DESIGN AND PARTICIPANTS: Using the nationally representative, population-based cohort of the Longitudinal Aging Study Amsterdam, 281 participants with clinically relevant depressive symptoms (Center for Epidemiological Studies Depression Scale ≥16) aged 55 years and older were followed longitudinally during a period of 6 years. MEASUREMENTS: Using a maximum of 14 successive Center for Epidemiological Studies Depression Scale observations, three clinical course types of depressive symptoms were defined. At baseline, general cognitive functioning was assessed using the Mini-Mental State Exam, memory performance (immediate recall and retention) by means of the auditory verbal learning test, and processing speed by means of a timed coding task. RESULTS: Remission, fluctuating course, and chronic course were seen in 22%, 50%, and 28%, respectively. In univariate analyses, a slowed processing speed was associated with a chronic course of depressive symptoms, as compared with remission (mean: 21.5, SD: 6.6, versus mean: 24.6, SD: 6.8, t = 2.78, df = 139, p < 0.001). Using multivariate regression techniques, this association remained significant after correcting for potential confounders and a number of risk factors for vascular brain damage (odds ratio: 1.08, 95% confidence interval: 1.01-1.14). Neither global cognitive functioning nor memory performance was associated with any course type of depressive symptoms. CONCLUSION: We found an independent association of a slowed processing speed with a poor natural course of depressive symptoms in older people. In clinical practice, when dealing with an older depressed person with comorbid cognitive decline, processing speed might be a more useful tool than the Mini-Mental State Exam in predicting the prognosis.

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.

The association between serum cortisol and cognitive decline in older persons.

OBJECTIVE: To investigate whether serum cortisol levels are associated with cognitive performance and cognitive decline in elderly persons and whether this association differs by age, sex, and depression status. DESIGN: Data from the Longitudinal Aging Study Amsterdam, with repeated measurements of cognitive performance after 3 and 6 years. PARTICIPANTS: A total of 1,154 persons, aged 65-88 years. MEASUREMENTS: Serum concentrations of total cortisol (CRT) and corticosteroid binding globulin (CBG) were measured at baseline, and from these free cortisol index (CRT/CBG) was computed. At baseline and 3 and 6 years of follow-up, global cognitive functioning, verbal memory performance, and speed of information processing were assessed. RESULTS: After adjustment for demographics, health, and life style variables, a significant association between high levels of free cortisol and poorer performance on verbal learning (B = -0.32; 95% confidence interval: -0.64 to -0.01) was found in both women and men. Additional adjustment for depression did not change this association. In women, but not in men, high levels of free cortisol (B = -0.85; 95% confidence interval: -1.40 to -0.31) were associated with slower speed of information processing. The associations between cortisol and cognitive performance were the same for the younger and the older old and for depressed and nondepressed persons. Higher levels of cortisol were not associated with cognitive decline over a period of 6 years. CONCLUSION: Our study provides further evidence that high levels of cortisol measured during the day are associated with lower memory function and speed of information processing but not with decline in cognitive functioning over 6 years of time.

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.

Personality characteristics and hypothalamic-pituitary-adrenal axis regulation in older persons.

OBJECTIVE: To investigate the cross-sectional association between personality characteristics and hypothalamic-pituitary-adrenal (HPA) axis regulation in older persons. METHODS: The study sample consisted of 1,150 participants (mean age 74.8 +/- 7.1 years, 48% male) from the population-based Longitudinal Aging Study Amsterdam. HPA axis activity was measured with salivary cortisol collected after awakening and late in the evening. Outcome measures were awakening and evening cortisol levels (natural log transformed) and the diurnal pattern of cortisol. Determinants were scores on questionnaires assessing neuroticism, mastery, and self-esteem. RESULTS: Multiple linear regression analyses adjusted for potential confounders did not show significant associations between any of the personality characteristics and any of the cortisol measures. On evening cortisol, a significant interaction was observed between neuroticism and age (B = -0.001; T = -2.50, df = 1,139; p value = 0.01). After stratification in two age groups, the authors observed that high levels of neuroticism were associated with elevated levels of evening cortisol in subjects aged <75 years (B = 0.02; 95% confidence interval: 0.01-0.03; T = 2.15, df = 630, p = 0.03) but not in subjects aged 75 years or older. CONCLUSIONS: The findings of this large population-based study of older persons suggest that the personality characteristics mastery and self-esteem are not associated with HPA axis regulation as measured with salivary awakening and evening cortisol. However, high neuroticism may be associated with elevated levels of evening cortisol in the younger old but not in the older old.

Late-life depression, cortisol, and the metabolic syndrome.

OBJECTIVES: High-cortisol levels in depressed persons could possibly give rise to the metabolic syndrome. This study investigated cross-sectionally whether depression and high-cortisol levels increased the odds of metabolic syndrome in an older community-based sample. METHODS: In 1,212 participants, aged > or =65 years, enrolled in the Longitudinal Aging Study Amsterdam, depression (major [1-month diagnosis] or subthreshold [no 1-month diagnosis, but symptoms]), metabolic syndrome (modified Adult Treatment Panel III criteria), and free cortisol index (total serum cortisol/cortisol binding globulin) were assessed. RESULTS: Major depression was not associated with the metabolic syndrome (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 0.54-2.49), but subthreshold depression was associated with a decreased odds (OR = 0.55, 95% CI = 0.37-0.82). Persons with higher levels of free cortisol index showed a higher odds of metabolic syndrome (OR per standard deviation increase = 1.21, 95% CI = 1.06-1.39). CONCLUSIONS: As persons with high-cortisol levels more often had metabolic syndrome, hypercortisolemia within depressed persons may increase the risk of metabolic syndrome.

The symptom profile of vascular depression.

OBJECTIVES: Vascular depression is regarded as a subtype of depression, especially in--but not limited strictly to--older persons, and characterized by a specific clinical presentation and an association with (cerebro)vascular risk and disease. It is also known that depression is a risk factor in the development of myocardial infarction. The possibility of identifying depressed subjects at risk of a first cardiac event by their clinical presentation in general practice would have significant implications. METHODS: We studied the baseline depression symptom profiles of subjects in the Longitudinal Aging Study Amsterdam and compared the profile of depressed subjects who had and had not suffered a first cardiac event at a follow-up after eight years. RESULTS: We could not confirm the specific symptom profile in depressed subjects who suffered from a first cardiac event at follow-up. Most notably, the presumed specific symptoms of vascular depression, psychomotor retardation, and anhedonia were not significantly associated with the occurrence of a first cardiac event at follow-up. CONCLUSIONS: In this large community study we failed to identify a difference in the depression symptom profile between incident cardiac and non-cardiac cases.