Impact of depersonalization on the course of depression: longitudinal observations from the gutenberg health study.

BACKGROUND: Symptoms of depersonalization (DP) and derealization (DR) are a risk factor for more severe impairment, non-response to various treatments, and a chronic course. In this study, we investigated the effects of DP/DR symptoms in patients with clinically significant depressive symptoms on clinical characteristics and various outcomes in a representative population-based sample with a 5-year follow-up. METHODS: The middle-aged sample comprised n = 10,422 persons at baseline, of whom n = 9,301 were free from depressive and DP/DR symptoms. N = 522 persons had clinically significant depression (PHQ-9 ≥ 10) and co-occurring DP/DR symptoms, and n = 599 persons had clinically significant depression (PHQ-9 ≥ 10) without DP/DR symptoms. RESULTS: There were substantial health disparities between persons with and without depression. These disparities concerned a wide range of life domains, including lower quality of the recalled early life experiences with the parents, current socioeconomic status, social integration (partnership, loneliness), current social and interpersonal stressors (family, work), functional bodily complaints (e.g., tinnitus, migraine, chest pain), unhealthy lifestyle, and the prevalence of already developed physical diseases. These disparities persisted to the 5-year follow-up and were exceptionally severe for depressed persons with co-occurring DP/DR symptoms. Among the depressed persons, the co-occurrence of DP/DR symptoms more than doubled the risk for recurrence or persistence of depression. Only 6.9% of depressed persons with DP/DR symptoms achieved remission at the 5-year follow-up (PHQ-9 < 5). Depression with and without co-occurring DP/DR worsened self-rated physical health significantly. The impact of depression with co-occurring DP/DR on the worsening of the self-rated physical health status was stronger than those of age and major medical diseases (e.g., heart failure). However, only depression without DP/DR was associated with mortality in a hazard regression analysis adjusted for age, sex, and lifestyle. CONCLUSIONS: The results demonstrated that DP/DR symptoms represent an important and easily assessable prognostic factor for the course of depression and health outcomes. Given the low remission rates for depression in general and depression with DP/DR in particular, efforts should be made to identify and better support this group, which is disadvantaged in many aspects of life.

Income and education predict elevated depressive symptoms in the general population: results from the Gutenberg health study.

BACKGROUND: Socioeconomic status (SES) has a strong association with depression or physical and mental health in general. However, as SES is a multifaceted construct these associations are not easy to explain. Further, there are several indicators and many studies only investigating two or less indicators at the same time. Therefore, this study aims to analyze the cross-sectional and longitudinal association of three defined SES dimensions (education, occupational position and household net-income) with the occurrence of elevated symptoms of depression relative to the impact of important covariates. METHODS: The study included observational data from 12,484 participants of the Gutenberg Health Study. The outcome was "elevated depressive symptoms" as defined by Patient Health Questionnaire (PHQ-2) ≥ 2 at the 2.5-year follow-up. Regression coefficients were adjusted for baseline covariates (age, sex, partnership, depression, anxiety, medical history of depressive or anxiety disorder and major medical diseases (MMD)) in addition to SES sum score and the three single indicators. We further examined interaction terms of the SES with sex, partnership and major medical diseases. We analyzed the sample stratified by elevated depressive symptoms at baseline, as we expected different trajectories in both subgroups. RESULTS: SES, education and household net-income were lower in the group of persons with PHQ-2 ≥ 2 at baseline, and they predicted the occurrence of PHQ-2 ≥ 2 at 2.5 year follow-up in the group of persons without elevated depressive symptoms at baseline after multivariable adjustment (SES: Odds Ratio (OR) 0.96, 0.95-0.98, p <  0.0001; education: OR 0.96, 0.93-0.99, p = 0.036; household net-income: OR 0.96, 0.92-0.99, p = 0.046) but not in the group of persons with elevated depressive symptoms at baseline. Further, we found that the impact of major medical diseases on the development of elevated depressive symptoms was buffered by high income. In addition, living in a partnership buffered the impact of a low occupational position. CONCLUSIONS: Regarding the SES, the dimensions education and household net-income seem to play the most important role for socioeconomic inequalities in persons in Mid-West Germany with depressive symptoms. TRIAL REGISTRATION: Reference no. 837.020.07; original vote: 22.3.2007, latest update: 20.10.2015.

New onset of depression in aging women and men: contributions of social, psychological, behavioral, and somatic predictors in the community.

BACKGROUND: Based on the vulnerability-stress model, we aimed to (1) determine new onset of depression in individuals who had not shown evidence of depression at baseline (5 years earlier) and (2) identify social, psychological, behavioral, and somatic predictors. METHODS: Longitudinal data of N = 10 036 participants (40-79 years) were evaluated who had no evidence of depression at baseline based on Patient Health Questionnaire (PHQ-9), no history of depression, or intake of antidepressants. Multivariate logistic regression models were used to predict the onset of depression. RESULTS: Prevalence of new cases of depression was 4.4%. Higher rates of women (5.1%) than men (3.8%) were due to their excess incidence <60 years of age. Regression analyses revealed significant social, psychological, behavioral, and somatic predictors: loneliness [odds ratio (OR) 2.01; 95% confidence interval (CI) 1.48-2.71], generalized anxiety (OR 2.65; 1.79-3.85), social phobia (OR 1.87; 1.34-2.57), panic (OR 1.67; 1.01-2.64), type D personality (OR 1.85; 1.47-2.32), smoking (OR 1.35; 1.05-1.71), and comorbid cancer (OR 1.58; 1.09-2.24). Protective factors were age (OR 0.88; 0.83-0.93) and social support (OR 0.93; 0.90-0.95). Stratified by sex, cancer was predictive for women; for men smoking and life events. Entered additionally, the PHQ-9 baseline score was strongly predictive (OR 1.40; 1.34-1.47), generalized anxiety became only marginally, and panic was no longer predictive. Other predictors remained significant, albeit weaker. CONCLUSIONS: Psychobiological vulnerability, stress, and illness-related factors were predictive of new onset of depression, whereas social support was protective. Baseline subclinical depression was an additional risk weakening the relationship between anxiety and depression by taking their overlap into account. Vulnerability factors differed between men and women.

CD40L contributes to angiotensin II-induced pro-thrombotic state, vascular inflammation, oxidative stress and endothelial dysfunction.

CD40 ligand (CD40L) is involved in the vascular infiltration of immune cells and pathogenesis of atherosclerosis. Additionally, T cell CD40L release causes platelet, dendritic cell and monocyte activation in thrombosis. However, the role of CD40L in angiotensin II (ATII)-driven vascular dysfunction and hypertension remains incompletely understood. We tested the hypothesis that CD40L contributes to ATII-driven vascular inflammation by promoting platelet-leukocyte activation, vascular infiltration of immune cells and by amplifying oxidative stress. C57BL/6 and CD40L-/- mice were infused with ATII (1 mg/kg/day for 7 days) using osmotic minipumps. Vascular function was recorded by isometric tension studies, and reactive oxygen species (ROS) were monitored in blood and heart by optical methods. Western blot, immunohistochemistry, FACS analysis and real-time RT-PCR were used to analyze immune cell distribution, pro-inflammatory cytokines, NAPDH oxidase subunits, T cell transcription factors and other genes of interest. ATII-treated CD40L-/- mice showed improved endothelial function, suppression of blood platelet-monocyte interaction (FACS), platelet thrombin generation (calibrated automated thrombography) and coagulation (bleeding time), as well as decreased oxidative stress in the aorta, heart and blood compared to wild-type mice. Moreover, ATII-treated CD40L-/- mice displayed decreased levels of TH1 cytokines released by splenic CD4⁺ T cells (ELISA) and lower expression levels of NOX-2, T-bet and P-selectin as well as diminished immune cell infiltration in aortic tissue compared to controls. Our results demonstrate that many ATII-induced effects on vascular dysfunction, such as vascular inflammation, oxidative stress and a pro-thrombotic state, are mediated at least in part via CD40L.

Peroxisome proliferator-activated receptor γ, coactivator 1α deletion induces angiotensin II-associated vascular dysfunction by increasing mitochondrial oxidative stress and vascular inflammation.

OBJECTIVE: Peroxisome proliferator-activated receptor γ, coactivator 1α (PGC-1α) is an important mediator of mitochondrial biogenesis and function. Because dysfunctional mitochondria might be involved in the pathogenesis of vascular disease, the current study was designed to investigate the effects of in vivo PGC-1α deficiency during chronic angiotensin II (ATII) treatment. APPROACH AND RESULTS: Although ATII infusion at subpressor doses (0.1 mg/kg per day for 7 days) did not cause vascular dysfunction in wild-type mice, it led to impaired endothelial-dependent and endothelial-independent relaxation in PGC-1α knockout mice. In parallel, oxidative stress was increased in aortic rings from ATII-treated PGC-1α knockout mice, whereas no change in nitric oxide production was observed. By using the mitochondrial-specific superoxide dye MitoSox and complex I inhibitor rotenone, we identified the mitochondrial respiratory chain as the major PGC-1α-dependent reactive oxygen species source in vivo, accompanied by increased vascular inflammation and cell senescence. In vivo treatment with the mitochondria-targeted antioxidant Mito-TEMPO partially corrected endothelial dysfunction and prevented vascular inflammation in ATII-treated PGC-1α mice, suggesting a causative role of mitochondrial reactive oxygen species in this setting. CONCLUSIONS: PGC-1α deletion induces vascular dysfunction and inflammation during chronic ATII infusion by increasing mitochondrial reactive oxygen species production.