Prospective associations of depression subtypes with cardio-metabolic risk factors in the general population.

The mechanisms and temporal sequence underlying the association between major depressive disorder (MDD) and cardio-metabolic diseases are still poorly understood. Recent research suggests subtyping depression to study the mechanisms underlying its association with biological correlates. Accordingly, our aims were to (1) assess the prospective associations of the atypical, melancholic and unspecified subtypes of MDD with changes of fasting glucose, high-density lipoprotein-cholesterol, triglycerides, systolic blood pressure and the incidence of the metabolic syndrome, (2) determine the potential mediating role of inflammatory marker or adipokine concentrations, eating behaviors and changes in waist circumference during follow-up. Data stemmed from CoLaus|PsyCoLaus, a prospective cohort study including 35-66-year-old randomly selected residents of an urban area. Among the Caucasian participants who underwent the physical and psychiatric baseline evaluations, 2813 (87% participation rate) also accepted the physical follow-up exam (mean follow-up duration=5.5 years). Symptoms of mental disorders were elicited using a semi-structured interview. The atypical MDD subtype, and only this subtype, was prospectively associated with a higher incidence of the metabolic syndrome (OR=2.49; 95% CI 1.30-4.77), a steeper increase of waist circumference (β=2.41; 95% CI 1.19-3.63) and independently of this, with a steeper increase of the fasting glucose level (β=131; 95% CI 38-225) during follow-up. These associations were not attributable to or mediated by inflammatory marker or adipokine concentrations, eating behaviors, comorbid psychiatric disorders or lifestyle factors. Accordingly, our results further support the subtyping of MDD and highlight the particular need for prevention and treatment of metabolic consequences in patients with atypical MDD

Prevalence and correlates of DSM-5 major depressive and related disorders in the community.

Although the DSM-5 has suggested the two new categories of Persistent Depressive Disorders (PDD) and Other Specified Depressive Disorders (OSDD), no study so far has applied the DSM-5 criteria throughout the range of depressive disorders. The aims of the present study were to 1) establish the lifetime prevalence of specific depressive disorders according to the new DSM-5 definitions in a community sample, and 2) determine their clinical relevance in terms of socio-demographic characteristics, comorbidity, course and treatment patterns. The semi-structured Diagnostic Interview for Genetic Studies was administered by masters-level psychologists to a random sample of an urban area (n=3720). The lifetime prevalence was 15.2% for PDD with persistent major depressive episode (MDE), 3.3% for PDD with pure dysthymia, 28.2% for Major Depressive Disorder (MDD) and 9.1% for OSDD. Subjects with PDD with persistent MDE were the most severely affected, followed by those with recurrent MDD, single episode MDD, PDD with pure dysthymia and OSDD and finally those without depressive disorders. Our data provide further evidence for the clinical significance of mild depressive disorders (OSDD), but cast doubt on the pertinence of lumping together PDD with persistent MDE and the former DSM-IV dysthymic disorder within the new PDD category

Aspirin and statin use and the subsequent development of depression in men and women: Results from a longitudinal population-based study.

OBJECTIVE: Low-grade chronic inflammation is one potential mechanism underlying the well-established association between major depressive disorder (MDD) and increased cardiovascular morbidity. Both aspirin and statins have anti-inflammatory properties, which may contribute to their preventive effect on cardiovascular diseases. Previous studies on the potentially preventive effect of these drugs on depression have provided inconsistent results. The aim of the present paper was to assess the prospective association between regular aspirin or statin use and the incidence of MDD. METHOD: This prospective cohort study included 1631 subjects (43.6% women, mean age 51.7 years), randomly selected from the general population of an urban area. Subjects underwent a thorough physical evaluation as well as semi-structured interviews investigating DSM-IV mental disorders at baseline and follow-up (mean duration 5.2 years). Analyses were adjusted for a wide array of potential confounders. RESULTS: Our main finding was that regular aspirin or statin use at baseline did not reduce the incidence of MDD during follow-up, regardless of sex or age (hazard ratios, aspirin: 1.19; 95%CI, 0.68-2.08; and statins: 1.25; 95%CI, 0.73-2.14; respectively). LIMITATIONS: Our study is not a randomized clinical trial and could not adjust for all potential confounding factors, information on aspirin or statin use was collected only for the 6 months prior to the evaluations, and the sample was restricted to subjects between 35 and 66 years of age. CONCLUSION: Our data do not support a large scale preventive treatment of depression using aspirin or statins in subjects aged from 35 to 66 years from the community

Low emotion-oriented coping and informal help-seeking behaviour as major predictive factors for improvement in major depression at 5-year follow-up in the adult community.

Given the broad range of biopsychosocial difficulties resulting from major depressive disorder (MDD), reliable evidence for predictors of improved mental health is essential, particularly from unbiased prospective community samples. Consequently, a broad spectrum of potential clinical and non-clinical predictors of improved mental health, defined as an absence of current major depressive episode (MDE) at follow-up, were examined over a 5-year period in an adult community sample. The longitudinal population-based PsyCoLaus study from the city of Lausanne, Switzerland, was used. Subjects having a lifetime MDD with a current MDE at baseline assessment were selected, resulting in a subsample of 210 subjects. Logistic regressions were applied to the data. Coping styles were the most important predictive factors in the present study. More specifically, low emotion-oriented coping and informal help-seeking behaviour at baseline were associated with the absence of an MDD diagnosis at follow-up. Surprisingly, neither formal help-seeking behaviour, nor psychopharmacological treatment, nor childhood adversities, nor depression subtypes turned out to be relevant predictors in the current study. The paramount role of coping styles as predictors of improvement in depression found in the present study might be a valuable target for resource-oriented therapeutic models. On the one hand, the positive impact of low emotion-oriented coping highlights the utility of clinical interventions interrupting excessive mental ruminations during MDE. On the other hand, the importance of informal social networks raises questions regarding how to enlarge the personal network of affected subjects and on how to best support informal caregivers

Tracing the associations between sex, the atypical and the combined atypical-melancholic depression subtypes: A path analysis.

BACKGROUND: Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. METHODS: The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. RESULTS: Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. LIMITATIONS: The use of cross-sectional data does not allow causal conclusions. CONCLUSIONS: This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care

Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study.

There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hsCRP) with mood disorders. The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models. Current combined MDD [β = 0.29, 95% confidence interval (CI) 0.03-0.55] and current atypical MDD (β = 0.32, 95% CI 0.10-0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up. The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated

Partially distinct combinations of psychological, metabolic and inflammatory risk factors are prospectively associated with the onset of the subtypes of Major Depressive Disorder in midlife.

Given the well known heterogeneity of Major Depressive Disorder (MDD), dividing this complex disorder into subtypes is likely to be a more promising approach to identify its determinants than to study it as a whole. In a prospective population-based cohort study (CoLaus|PsyCoLaus) with 5.5 years of follow-up, 1524 participants without MDD at baseline, aged 35-66 years (mean age 51.4 years, 43.4% females), participated in the physical and psychiatric baseline and the psychiatric follow-up evaluations. The incidence of both atypical and melancholic MDD during the follow-up period were predicted by female sex, a lifetime history of minor depressive disorders and higher neuroticism scores. Higher baseline body mass index was associated with the onset of atypical MDD, whereas the absence of hypertension and younger age were associated with the development of melancholic MDD. Unspecified MDD was predicted by younger age, low concentrations of tumor necrosis factor-α and elevated life-event impact scores. The age range of our cohort restricts the identification of risk factors to MDD with onset in midlife and the recruitment in an urban area limits the generalizability of the findings. Our data suggest that MDD subtypes are predicted by partially distinct combinations of baseline characteristics suggesting that these subtypes not only differ in their clinical manifestations but also in factors that contribute to their development. Subjects with minor depressive episodes, especially in combination with particular personality features, deserve close clinical attention to prevent the subsequent onset of atypical and melancholic major depression

Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community.

The complex relationship between psychosocial stress over the lifetime, psychological factors, and cardiometabolic risk is still poorly understood. Accordingly, our aims were (1) to independently assess the associations between childhood adversity, life-event stress in remote (earlier than the last 5 years), and recent adulthood and cardiometabolic risk, and (2) to determine the role of psychological factors including personality, coping, and depression in these associations. The sample included 2674 adults, aged 35 to 66 years, randomly selected from urban area. Participants underwent a physical examination including the assessment of obesity markers, blood pressure, and blood lipid and glucose levels. Stress during adulthood was determined using the severity scores of 52 stressful life events. Information on adverse childhood experiences and major depressive disorders was collected using semistructured interviews, whereas personality traits and coping mechanisms were evaluated through questionnaires. Both childhood adversity and stress in remote adulthood were associated with elevated body mass index (β [95% confidence interval {CI}] = 0.249 [0.029 to 0.468]; 0.020 [0.006 to 0.034]), waist circumference (β [95% CI] = 0.061 [0.024 to 0.099]; 0.08 [0.04 to 0.11]), and the global cardiometabolic risk score (β [95% CI] = 0.278 [0.017 to 0.540]; 0.017 [0.001 to 0.033]) after adjustment for sociodemographic, lifestyle, and psychological factors. In addition, childhood adversity was associated with low high density lipoprotein levels (β [95% CI] = -0.021 [-0.042 to 0.000]), as well as increased fat mass and systolic blood pressure levels (β [95% CI] = 0.506 [0.165 to 0.846]; 0.952 [0.165 to 1.740]) and stress in remote adulthood with apolipoprotein B levels (β [95% CI] = 0.607 [0.312 to 0.901]). Psychological factors did not account for these associations and were not effect modifiers. Our data demonstrate that psychosocial stress during childhood and remote adulthood favor adiposity and abnormal lipid metabolism

Associations between mood, anxiety or substance use disorders and inflammatory markers after adjustment for multiple covariates in a population-based study.

Inflammation is one possible mechanism underlying the associations between mental disorders and cardiovascular diseases (CVD). However, studies on mental disorders and inflammation have yielded inconsistent results and the majority did not adjust for potential confounding factors. We examined the associations of several pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and high sensitive C-reactive protein (hsCRP) with lifetime and current mood, anxiety and substance use disorders (SUD), while adjusting for multiple covariates. The sample included 3719 subjects, randomly selected from the general population, who underwent thorough somatic and psychiatric evaluations. Psychiatric diagnoses were made with a semi-structured interview. Major depressive disorder was subtyped into "atypical", "melancholic", "combined atypical-melancholic" and "unspecified". Associations between inflammatory markers and psychiatric diagnoses were assessed using multiple linear and logistic regression models. Lifetime bipolar disorders and atypical depression were associated with increased levels of hsCRP, but not after multivariate adjustment. After multivariate adjustment, SUD remained associated with increased hsCRP levels in men (β = 0.13 (95% CI: 0.03,0.23)) but not in women. After multivariate adjustment, lifetime combined and unspecified depression were associated with decreased levels of IL-6 (β = -0.27 (-0.51,-0.02); β = -0.19 (-0.34,-0.05), respectively) and TNF-α (β = -0.16 (-0.30,-0.01); β = -0.10 (-0.19,-0.02), respectively), whereas current combined and unspecified depression were associated with decreased levels of hsCRP (β = -0.20 (-0.39,-0.02); β = -0.12 (-0.24,-0.01), respectively). Our data suggest that the significant associations between increased hsCRP levels and mood disorders are mainly attributable to the effects of comorbid disorders, medication as well as behavioral and physical CVRFs

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%