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Abstract Age-related cognitive decline has become an increasingly relevant public health issue. However, risk and protective factors of cognitive decline have yet to be investigated prospectively taking into account genetic, lifestyle, physical and mental health factors. Population-based data from middle-aged (40 to 59 years; N = 2,764) and older individuals (60 to 80 years; N = 1,254) were drawn from a prospective community cohort study using the Tower of London (TOL) planning task. Assessments were repeated at a 5-year interval to investigate age-related changes in planning performance and to determine the impact of risk and protective factors. Planning performance improved in middle-aged, but declined in older participants over 5 years. SNPs affecting the dopamine system (COMT, DRD2) and APOE polymorphisms differentially predicted cognitive performance in older vs. middle-aged individuals. For older individuals, high alcohol consumption, antidepressant medication and living without a partner had additional negative predictive power on cognition. In contrast, undiagnosed hypertension, no obstructive lung disease, and fewer years of education predicted cognitive decline in the middle-aged group. The results inform screening for individuals particularly vulnerable to cognitive decline and interventions (e.g., focusing on lifestyle factors) to help maintain cognitive performance into old age.

Abstract Research indicates that patients with a lifetime history of suicide attempts are particularly burdened. However, investigations of their characteristics and comparisons with other patients are scarce. This study aimed to fill this research gap, using routine clinical data and guided by theoretical models. Data of N = 706 patients (54.4% women) was collected at the psychosomatic inpatient/day-clinic unit of a German university clinic. It comprised sociodemographic data and information about previous experiences (e.g., childhood abuse and neglect), symptom measures (e.g., the PHQ-9) and individual differences (e.g., the level of personality functioning assessed with the OPD-SQS). Groups were compared using independent t-tests or χ2-tests. Of the total sample, 118 patients (16.7%) reported suicide attempts. Those with a history of suicide attempts were more likely to have a migration background and a lower level of education, smoke (heavily) and use illegal substances. They reported lower levels of personality functioning, more current symptoms and traumatic previous experiences of abuse and neglect. Screening for previous suicidal behavior as well as associated factors can yield valuable information for clinical practice. Many group differences map onto previously observed specific risk factors for suicidal behavior, supporting the conceptual models and underscoring their relevance among clinical populations as well.

Abstract The relationship between noise annoyance and risk of cardiovascular disease (CVD) still needs to be fully elucidated. Thus, we examined the relationship between noise annoyance and CVD risk in a large population-based cohort study. Cross-sectional (N = 15,010, aged 35–74 years, baseline investigation period 2007–2012) and prospective data (5- and 10-year follow-up from 2012 to 2022) from the Gutenberg Health Study were used to examine the relationship between noise annoyance due to different sources and risk of prevalent and incident CVD comprising atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and venous thromboembolism. In cross-sectional analyses, noise annoyance was an independent risk factor for prevalent CVD, with the strongest associations seen for noise annoyance during sleep (e.g., neighborhood noise annoyance: odds ratio 1.20, 95% confidence interval 1.13–1.27, p

Abstract 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

Introduction: Overweight and obesity lead to numerous complications and their treatment. The associated costs represent a health and sociopolitical burden. Therefore, the development of overweight and obesity is of great importance for health policy. Methods: The Gutenberg Health Study (GHS), a population-based observational study of individuals aged 35–74 years in the city of Mainz and the district of Mainz-Bingen, examined current data on the prevalence and development of overweight and obesity and their association with concomitant diseases and medication use. Results: Among men, 48.1% were overweight and 26.3% had obesity. Among women, these proportions were 32.1% and 24.1%, respectively. Elevated body mass index (BMI) was associated with numerous complications, particularly insulin resistance and type 2 diabetes, arterial hypertension, elevated triglycerides and low HDL cholesterol, and cardiovascular disease. Accordingly, medications to treat these conditions were used significantly more often in individuals with elevated BMI. During the 10-year observation period, mean weight increased in the population. Both men and women had a moderate but significant increase in BMI compared to men and women of the same age at baseline. Individual weight changes over the 10-year observation period, on the other hand, were age-dependent. In the two younger age decades, weight gain was observed, while in the oldest age decade, mean body weight decreased. Conclusion: These current data confirm that overweight and obesity are associated with relevant complications and that these complications lead to significant use of appropriate medications. The study also suggests that there is a significant trend toward increased prevalence of obesity (BMI ≥30) over the 10-year period.

Abstract Previous studies reported significantly altered tryptophan catabolite concentrations in major depression. Thus, tryptophan catabolites were considered as potential biomarkers of depression and their modulators as potential targets for psychopharmacotherapy. However, the results were based mainly on studies with small sample sizes limiting their generalizability. Against this background, we investigated the relationship of peripheral tryptophan catabolites with depression in a population-based sample with n = 3,389 participants (with fasting status ≥ 8 h and C-reactive protein

Abstract Background Gambling Disorder (GD) has been associated with considerable mental and physical health risks in clinical samples. The paper determines risk factors, mental and physical health burden of probable GD for both men and women in the general population. Methods In the Gutenberg Health Study, a population-based sample of N = 11,875 aged 40–80 years was analyzed regarding lifetime probable GD prevalence (measured with the Lie/ Bet Questionnaire) and a wide array of health variables including standardized measures of depression, anxiety, and somatic symptoms. Results Probable GD lifetime prevalence was 2.1%, with higher rates among 1st generation migrants (5.5%; vs. non-migrants 1.6%), men (3.0%; vs. women 1.2%), and the sample’s youngest age decade (40–49 y., 3.1%). Lifetime probable GD was associated with current work-related, family and financial stressors as well as unhealthy behavior (smoking, extended screen time), and lifetime legal offenses. In men, but not in women, increased rates of imprisonment, mental and somatic symptoms were found. Conclusions GD is a major public health problem with serious social, mental and physical health burden. Epidemiological findings underscore the preponderance of GD among 1st generation migrants and men. Findings are consistent with a vicious cycle of family, work related and financial stress factors, and mental and physical burden, particularly in men. Demographic risk factors may help to target specific prevention and treatment efforts.

Abstract Depression has been associated with increased inflammation. However, only few large-scale, prospective studies have evaluated whether inflammation leads to new cases of depression and whether this association can be found in men and women. Longitudinal data of N = 10,357 adult participants with no evidence of depression at baseline (based on Patient Health Questionnaire (PHQ-9), lifetime diagnoses, and current antidepressant medication) were evaluated for depression 5 years later. Multivariate logistic regression models were used to predict the onset of depression based on C-reactive protein (CRP) and white blood cell count (WBC). We used interaction terms and separate analyses in men and women to investigate gender-dependent associations. Based on both markers, inflammation was predictive of new cases of depression 5 years later, even when adjusting for sociodemographic, physical health, health behavior variables, and baseline depression symptoms. As established by interaction terms and separate analyses, inflammatory markers were predictive of depression in men, but not in women. Additional predictors of new onset of depression were younger age, loneliness, smoking (only in men), cancer and less alcohol consumption (only in women). The study indicates gender differences in the etiology of depressive disorders within the community, with a greater role of physical factors in men.

Abstract Background Coronary heart disease (CHD) is the leading cause of death and years of life lost worldwide. While effective treatments are available for both acute and chronic disease stages there are unmet needs for effective interventions to support patients in health behaviors required for secondary prevention. Psychosocial distress is a common comorbidity in patients with CHD and associated with substantially reduced health-related quality of life (HRQoL), poor health behavior, and low treatment adherence. Methods In a confirmatory, randomized, controlled, two-arm parallel group, multicenter behavioral intervention trial we will randomize 440 distressed CHD patients with at least one insufficiently controlled cardiac risk factor to either their physicians' usual care (UC) or UC plus 12-months of blended collaborative care (TeamCare = TC). Trained nurse care managers (NCM) will proactively support patients to identify individual sources of distress and risk behaviors, establish a stepwise treatment plan to improve self-help and healthy behavior, and actively monitor adherence and progress. Additional e-health resources are available to patients and their families. Intervention fidelity is ensured by a treatment manual, an electronic patient registry, and a specialist team regularly supervising NCM via videoconferences and recommending protocol and guideline-compliant treatment adjustments as indicated. Recommendations will be shared with patients and their physicians who remain in charge of patients’ care. Since HRQoL is a recommended outcome by both, several guidelines and patient preference we chose a ≥ 50% improvement over baseline on the HeartQoL questionnaire at 12 months as primary outcome. Our primary hypothesis is that significantly more patients receiving TC will meet the primary outcome criterion compared to the UC group. Secondary hypotheses will evaluate improvements in risk factors, psychosocial variables, health care utilization, and durability of intervention effects over 18–30 months of follow-up. Discussion TEACH is the first study of a blended collaborative care intervention simultaneously addressing distress and medical CHD risk factors conducted in cardiac patients in a European health care setting. If proven effective, its results can improve long-term chronic care of this vulnerable patient group and may be adapted for patients with other chronic conditions. Trial registration: German Clinical Trials Register, DRKS00020824, registered on 4 June, 2020; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020824

Abstract Background Studies in immigrant youth have suggested differences in parenting patterns by immigration status. Knowledge of variation in recalled parenting pattern and its distinctive impact on mental health in adult immigrants, however, is limited. Therefore, the purpose of the current study was to investigate similarities and differences in recalled maternal and paternal rearing behavior and its association with depressiveness in adult 1st generation immigrants compared to non-immigrants. Methods Seven hundred and forty-three 1st generation immigrants (M = 57.4, SD = 10.1 years) and 6518 non-immigrants (M = 60.3, SD = 10.7 years) participated in a population-based study. Regarding countries of origin, the largest subgroups were immigrants from Eastern-Europe, Former-SU, and Arabic-Islamic countries. All participants completed the ultra-short version of The Recalled Parental Rearing Behavior-questionnaire and the PHQ-9 assessing depressiveness. Multiple linear regressions with depressiveness as outcome variable were analyzed separately for each facet of parental rearing behavior adjusting for socio-demographic and migration-related variables. Results In addition to differences in depressiveness and socioeconomic status, 1st generation immigrants recalled both their mothers and fathers as more controlling and overprotecting than non-immigrants. Parental emotional warmth was negatively associated with depressiveness across all groups. The relationship between parental control, respectively parental rejection and depressiveness, however, varied in direction and severity between the groups. Conclusion The results support the notion that parental warmth is a universal protective factor against depressiveness, whereas the impact of parental control on mental health might be more culturally influenced. Analyses point to the importance of considering the unique contribution of fathers’ rearing behavior on mental health, particularly in immigrant samples.

Abstract To investigate the prevalence and new onset of depression and anxiety among subjects with age-related macular degeneration (AMD) and its association with AMD in a large European cohort with relatively good visual acuity. 11,834 participants enrolled in the German population-based Gutenberg Health Study were studied. AMD was diagnosed by grading of fundus photographs. Depression and anxiety were assessed with the Patient Health Questionnaire and the Generalized Anxiety Disorder-2 Scale, respectively. Logistic regression analyses were performed and adjusted for several parameters. 1,089 (9.2%) participants were diagnosed having AMD. Prevalence of depression in AMD and non-AMD participants was 7.2% and 8.0%, respectively and prevalence of anxiety was 4.2% and 7.0%, respectively. New onset of depression and anxiety at 5-year follow-up in AMD subjects was 2.6% and 3.6%, respectively. AMD was not associated with depression (OR 0.93; CI 95% 0.70–1.20; p = 0.62). AMD was associated with less anxiety (OR 0.67; CI 95% 0.47–0.93; p = 0.02). This is the first study analyzing both prevalence and new onset of depression and anxiety in AMD subjects. AMD- and non-AMD participants had a similar prevalence and new onset of depression in our population-based sample. Participants without AMD had a higher prevalence of anxiety. AMD was not associated with depression.

Purpose We investigated the association between social inequality and participation in a mammography screening program (MSP). Since the German government offers mammography screening free of charge, any effect of social inequality on participation should be due to educational status and not due to the financial burden. Methods The ‘Gutenberg Health Study’ is a cohort study in the Rhine-Main-region, Germany. A health check-up was performed, and questions about medical history, health behavior, including secondary prevention such as use of mammography, and social status are included. Two indicators of social inequality (equivalence income and educational status), an interaction term of these two, and different covariables were used to explore an association in different logistic regression models. Results A total of 4,681 women meeting the inclusion criteria were included. Only 6.2% never participated in the MSP. A higher income was associated with higher chances of ever participating in a mammography screening (odds ratios (OR): 1.67 per €1000; 95%CI:1.26–2.25, model 3, adjusted for age, education and an interaction term of income and education). Compared to women with a low educational status, the odds ratios for ever participating in the MSP was lower for the intermediate educational status group (OR = 0.64, 95%CI:0.45–0.91) and for the high educational status group (0.53, 95%CI:0.37–0.76). Results persisted also after controlling for relevant confounders. Conclusions Despite the absence of financial barriers for participation in the MSP, socioeconomic inequalities still influence participation. It would be interesting to examine whether the educational effect is due to an informed decision.

Abstract 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

Abstract Background Depressive symptoms are common in patients with coronary artery disease (CAD) and are associated with an unfavourable outcome. Establishing prognostic patient profiles prior to the beginning of mental health care may facilitate higher efficacy of targeted interventions. The aim of the current study was to identify sociodemographic and somatic predictors of depression outcome among depressed patients with CAD. Methods Based on the dataset of the multicentre SPIRR-CAD randomised controlled trial (n = 570 patients with CAD and ≥ 8 points on the Hospital Anxiety and Depression Scale (HADS)), 141 potential sociodemographic and somatic predictors of the change in the HADS-D depression score from baseline to 18-month-follow-up were derived in two different ways. We screened for univariable association with response, using either analysis of (co)variance or logistic regression, respectively, both adjusted for baseline HADS-D value and treatment group. To guard against overfitting, multivariable association was evaluated by a linear or binomial (generalised) linear model with lasso regularisation, a machine learning approach. Outcome measures were the change in continuous HADS-D depression scores, as well as three established binary criteria. The Charlson Comorbidity Index (CCI) was calculated to assess possible influences of comorbidities on our results and was also entered in our machine learning approach. Results Higher age (p = 0.002), unknown previous myocardial infarction (p = 0.013), and a higher heart rate variability during numeracy tests (p = .020) were univariably associated with a favourable depression outcome, whereas hyperuricemia (p ≤ 0.003), higher triglycerides (p = 0.014), NYHA class III (p ≤ 0.028), state after resuscitation (p ≤ 0.042), intake of thyroid hormones (p = 0.007), antidiabetic drugs (p = 0.015), analgesic drugs (p = 0.027), beta blockers (p = 0.035), uric acid drugs (p ≤ 0.039), and anticholinergic drugs (p = 0.045) were associated with an adverse effect on the HADS-D depression score. In all analyses, no significant differences between study arms could be found and physical comorbidities also had no significant influence on our results. Conclusion Our findings may contribute to identification of somatic and sociodemographic predictors of depression outcome in patients with CAD. The unexpected effects of specific medication require further clarification and further research is needed to establish a causal association between depression outcome and our predictors. Trial registration www.clinicaltrials.gov NCT00705965 (registered 27th of June, 2008). www.isrctn.com ISRCTN76240576 (registered 27th of March, 2008).

Abstract Background It has been shown, that in the general population psychosocial stress affects health behaviors. However similar studies of high risk populations are sparse. Therefore, the aim of this cross-sectional study is to analyze the association between common psychosocial stressors and health behavior in a sample of patients with mental disorders. Methods We analyzed data of n = 2326 outpatients from a mental health care department. Severity of psychosocial stress was assessed by the PHQ-stress module of the Patient Health Questionnaire (PHQ). Health behaviors included obesity, uncontrolled eating, smoking and physical inactivity. Multiple binary regression models were conducted for the PHQ-stress score and for each of the ten PHQ-stress items as independent variables. Results 'Financial stress' and 'having no one to turn to with problems' were mainly associated with adverse health behaviors after adjustment for multivariate effects. The most affected health behaviors were uncontrolled eating in both sexes and obesity in women. Conclusion Our findings indicate specific influences of psychosocial stressors on unhealthy behaviors in a clinical sample. Patients with financial strain and lack of social support might need specific support for improving their health behavior.

Aims: Cigarette smoking is one of the most complex and least understood cardiovascular risk factors. Importantly, differences in the tobacco-related pathophysiology of endothelial dysfunction, an early event in atherogenesis, between circulatory beds remain elusive. Therefore, this study evaluated how smoking impacts endothelial function of conduit and resistance arteries in a large population-based cohort.Methods and results: 15,010 participants (aged 35–74 years) of the Gutenberg Health Study were examined at baseline from 2007 to 2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a computer-assisted interview. Endothelial function of conduit and resistance arteries was determined by flow-mediated dilation (FMD) of the brachial artery, reactive hyperemia index (RHI) using peripheral arterial tonometry, as well as by reflection index (RI) derived from digital photoplethysmography, respectively. Among all subjects, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Mean cumulative smoking exposure was 22.1 ± 18.1 pack-years in current smokers and mean years since quitting was 18.9 ± 12.7 in former smokers. In multivariable linear regression models adjusted for typical confounders, smoking status, pack-years of smoking, and years since quitting smoking were independently associated with RHI and RI, while no association was found for FMD. Overall, no clear dose-dependent associations were observed between variables, whereby higher exposure tended to be associated with pronounced resistance artery endothelial dysfunction.Conclusions: Cigarette smoking is associated with altered endothelial function of resistance, but not conduit arteries. The present results suggest that smoking-induced endothelial dysfunction in different circulatory beds may exhibit a differential picture.

Psychosocial stress has a profound impact on well-being and health. The response to stress is associated mainly with the amygdala, a crucial structure of the fear-defense system, essential for social cognition and emotion regulation. Recent neuroimaging-studies demonstrated how an increased metabolic activity of the amygdala enhances inflammation, and leads to cardiometabolic disease. The development of therapeutic strategies depends on our understanding of both which factors activate the fear-defense system and the subsequent molecular mechanisms that translate emotional stress into cell damage. Fear of emotions as an aftermath of attachment trauma is the most important trigger of the maladaptive activation of the fear-defense system. The central molecular pathways are enhanced myelopoiesis and upregulated proinflammatory gene expression, glucocorticoid and insulin resistance, and oxidative stress. Therapeutic strategies may benefit from holistic approaches. Psychotherapy can reduce the maladaptively increased activation of the fear-defense system. Biological interventions can buffer the detrimental effects of oxidative stress in the organism.

Abstract Background A growing number of studies have associated metabolic syndrome (MetS) and depression, both retrospectively and prospectively. However, it has remained unclear, which degrees, or sub-dimensions of depression are related to MetS and if comorbid depression affects health care utilization. The purpose of the study was to determine the associations of a) somatic and cognitive-affective symptoms to MetS and b) depression and MetS to health care utilization. Methods In a population-based, representative survey of 14.499 participants we studied the associations of the two dimensions of depression with MetS and health care utilization. Depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9). Results MetS and its components were associated with the degree of depression, particularly with moderately severe/ severe depressive symptoms (PHQ-9 > = 15). There were clear positive associations of somatic-affective depressive symptoms with the presence of MetS and its components. Cognitive-affective symptoms were negatively associated with MetS. At the single item level, disorders of sleep and appetite as well as exhaustion were positively, while trouble concentrating was negatively associated with MetS. Symptoms of depression were related to higher consultations of somatic and mental health care, while the presence of MetS was related to somatic health care utilization. There was an additional interaction of depressive symptoms and MetS with mental health care. Conclusions Somatic affective symptoms of depression are positively associated, while cognitive-affective symptoms are negatively associated with MetS.

Abstract Background A short screening for social anxiety disorder is useful in clinical and epidemiological contexts. However, the German version of the short form of the Social Phobia Inventory (mini-SPIN) has not been evaluated yet. Therefore, our aim was to determine reliability, validity and population based norms of the German mini-SPIN. Methods The mini-SPIN was evaluated in a clinical (N = 1254) and in a representative community sample (N = 1274). Clinical diagnoses, the Patient Health Questionnaire depression (PHQ-9) and somatization modules (PHQ-15), the Generalized Anxiety Disorder Scale (GAD-7), the Liebowitz Social Anxiety Scale (LSAS), and the Short-Form-12 Health Survey (SF-12) were used in the clinical sample. In the community sample, participants filled out socio-demographic and health related questions and short versions of the PHQ (PHQ-2, GAD-2, panic item). Internal consistency, test-retest reliability, sensitivity to change, discriminant validity, and convergent validity were examined. Receiver operating characteristic curve analyses were performed to determine cut-off scores. Population based norms were computed from the community sample. Results We found internal consistencies between 0.80 and 0.83. Test-retest correlation was Rho = 0.61; sensitivity to change was comparable to the LSAS. Correlations indicated good convergent and discriminant validity of the mini-SPIN. Strict measurement invariance can be assumed regarding age and gender. Receiver operating characteristic curve analysis suggested a cut-off of 6 or higher for a probable diagnosis of SAD. Conclusions The German version of the mini-SPIN is a reliable and valid instrument. Its brevity makes it valuable for screening and assessing changes of social anxiety in clinical and epidemiological studies.

Abstract Background To estimate the burden of diseases, it is important to consider patient-reported outcomes including Quality of Life (QoL). The aim of this study is to provide population-based reference data for the National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25), stratified by sex and age. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74. The baseline examination was conducted between 2007 and 2012. To overcome known shortcomings of the NEI VFQ-25, we calculated the previously proposed visual functioning scale and the socio-emotional scale based on Rasch-transformed person-level data. We present mean values, standard deviations and percentiles for age decades stratified by sex. We used a linear regression model to assess the influence of age, sex, socioeconomic status, distance-corrected visual acuity (better-seeing eye) and the absolute difference in distance-corrected visual acuity of both eyes on vision-related QoL. Results NEI VFQ-25 data are available from 12,231 participants (82%). Both the long-form visual functioning scale (LFVFS) and the long-form socio-emotional scale (LFSES) showed a clear age dependency, with an average LFVFS score of 92.8 for men and 90.5 for women in the youngest age group and 85.7 and 83.4 in the oldest age group, and a LFSES score of 98.3 for men and 98.1 in women in the youngest and 94.7 and 94.5 in the oldest decade. The largest difference was observed between the youngest age group (35–44 years) and the 45–54 years group. Men tended to have slightly higher scores than women. In the multivariable linear regression analysis, age (per 5 years −0.42), female sex (−1.57), worse distance-corrected visual acuity of the better eye (per 0.1 increase in logMAR −2.92) and the difference between both eyes (per 0.1 increase in logMAR −0.87) were associated with a reduced LFVFS score (all p

Aim of the study was the development and validation of the psychometric properties of a six-item bi-factorial instrument for the assessment of social support (emotional and tangible support) with a population-based sample. A cross-sectional data set of N = 15,010 participants enrolled in the Gutenberg Health Study (GHS) in 2007-2012 was divided in two sub-samples. The GHS is a population-based, prospective, observational single-center cohort study in the Rhein-Main-Region in western Mid-Germany. The first sub-sample was used for scale development by performing an exploratory factor analysis. In order to test construct validity, confirmatory factor analyses were run to compare the extracted bi-factorial model with the one-factor solution. Reliability of the scales was indicated by calculating internal consistency. External validity was tested by investigating demographic characteristics health behavior, and distress using analysis of variance, Spearman and Pearson correlation analysis, and logistic regression analysis. Based on an exploratory factor analysis, a set of six items was extracted representing two independent factors. The two-factor structure of the Brief Social Support Scale (BS6) was confirmed by the results of the confirmatory factor analyses. Fit indices of the bi-factorial model were good and better compared to the one-factor solution. External validity was demonstrated for the BS6. The BS6 is a reliable and valid short scale that can be applied in social surveys due to its brevity to assess emotional and practical dimensions of social support.

OBJECTIVES:Little is known about patient characteristics as predictors for outcome in manualized short term psychodynamic psychotherapy (PDT). No study has addressed which patient variables predict outcome of PDT for social anxiety disorder. RESEARCH DESIGN AND METHODS:In the largest multicenter trial on psychotherapy of social anxiety (SA) to date comparing cognitive therapy, PDT and wait list condition N = 230 patients were assigned to receive PDT, of which N = 166 completed treatment. Treatment outcome was assessed based on diverse parameters such as endstate functioning, remission, response, and drop-out. The relationship between patient characteristics (demographic variables, mental co-morbidity, personality, interpersonal problems) and outcome was analysed using logistic and linear regressions. RESULTS:Pre-treatment SA predicted up to 39 percent of variance of outcome. Only few additional baseline characteristics predicted better treatment outcome (namely, lower comorbidity and interpersonal problems) with a limited proportion of incremental variance (5.5 to 10 percent), while, e.g., shame, self-esteem or harm avoidance did not. CONCLUSIONS:We argue that the central importance of pre-treatment symptom severity for predicting outcomes should advocate alternative treatment strategies (e.g. longer treatments, combination of psychotherapy and medication) in those who are most disturbed. Given the relatively small amount of variance explained by the other patient characteristics, process variables and patient-therapist interaction should additionally be taken into account in future research. TRIAL REGISTRATION:Controlled-trials.com/ISRCTN53517394.

BACKGROUND:While noise annoyance has become recognized as an important environmental stressor, its association to mental health has hardly been studied. We therefore determined the association of noise annoyance to anxiety and depression and explored the contribution of diverse environmental sources to overall noise annoyance. PATIENTS AND METHODS:We investigated cross-sectional data of n = 15.010 participants of the Gutenberg Health Study (GHS), a population-based, prospective, single-center cohort study in Mid-Germany (age 35 to 74 years). Noise annoyance was assessed separately for road traffic, aircraft, railways, industrial, neighborhood indoor and outdoor noise ("during the day"; "in your sleep") on 5-point scales ("not at all" to "extremely"); depression and anxiety were assessed by the PHQ-9, resp. GAD-2. RESULTS:Depression and anxiety increased with the degree of overall noise annoyance. Compared to no annoyance, prevalence ratios for depression, respectively anxiety increased from moderate (PR depression 1.20; 95%CI 1.00 to 1.45; PR anxiety 1.42; 95% CI 1.15 to 1.74) to extreme annoyance (PR depression 1.97; 95%CI 1.62 to 2.39; PR anxiety 2.14; 95% CI 1.71 to 2.67). Compared to other sources, aircraft noise annoyance was prominent affecting almost 60% of the population. INTERPRETATION:Strong noise annoyance was associated with a two-fold higher prevalence of depression and anxiety in the general population. While we could not relate annoyance due to aircraft noise directly to depression and anxiety, we established that it was the major source of annoyance in the sample, exceeding the other sources in those strongly annoyed. Prospective follow-up data will address the issue of causal relationships between annoyance and mental health.

Smoking is a major risk factor for cardiovascular diseases and has been implicated in the regulation of the G protein-coupled receptor 15 (GPR15) by affecting CpG methylation. The G protein-coupled receptor 15 is involved in angiogenesis and inflammation. An effect on GPR15 gene regulation has been shown for the CpG site CpG3.98251294. We aimed to analyze the effect of smoking on GPR15 expression and methylation sites spanning the GPR15 locus. DNA methylation of nine GPR15 CpG sites was measured in leukocytes from 1291 population-based individuals using the EpiTYPER. Monocytic GPR15 expression was measured by qPCR at baseline and five-years follow up. GPR15 gene expression was upregulated in smokers (beta (ß) = −2.699, p-value (p) = 1.02 × 10−77) and strongly correlated with smoking exposure (ß = −0.063, p = 2.95 × 10−34). Smoking cessation within five years reduced GPR15 expression about 19% (p = 9.65 × 10−5) with decreasing GPR15 expression over time (ß = 0.031, p = 3.81 × 10−6). Additionally, three novel CpG sites within GPR15 affected by smoking were identified. For CpG3.98251047, DNA methylation increased steadily after smoking cessation (ß = 0.123, p = 1.67 × 10−3) and strongly correlated with changes in GPR15 expression (ß = 0.036, p = 4.86 × 10−5). Three novel GPR15 CpG sites were identified in relation to smoking and GPR15 expression. Our results provide novel insights in the regulation of GPR15, which possibly linked smoking to inflammation and disease progression.

ObjectivesWhile a bidirectional relationship between diabetes and depression has been established, there is little knowledge if the associations are due to somatic-affective or cognitive-affective dimensions of depression.Research design and methodsIn a population-based, representative survey of 15.010 participants we therefore studied the associations of the two dimensions of depression with diabetes and health care utilization among depressed and diabetic participants. Depression was assessed by the Patient Health Questionnaire PHQ-9.ResultsWe found a linear and consistent association between the intensity of depression and the presence of diabetes increasing from 6.9% in no or minimal depression to 7.6% in mild, 9% in moderate and 10.5% in severe depression. There was a strong positive association between somatic-affective symptoms but not with cognitive-affective symptoms and diabetes. Depression and diabetes were both independently related to somatic health care utilisation.ConclusionsDiabetes and depression are associated, and the association is primarily driven by the somatic-affective component of depression. The main limitation of our study pertains to the cross-sectional data acquisition. Further longitudinal work on the relationship of obesity and diabetes should differentiate the somatic and the cognitive symptoms of depression.

Cell-free DNA (cfDNA) in body tissues or fluids is extensively investigated in clinical medicine and other research fields. In this article we provide a direct quantitative real-time PCR (qPCR) as a sensitive tool for the measurement of cfDNA from plasma without previous DNA extraction, which is known to be accompanied by a reduction of DNA yield. The primer sets were designed to amplify a 90 and 222 bp multi-locus L1PA2 sequence. In the first module, cfDNA concentrations in unpurified plasma were compared to cfDNA concentrations in the eluate and the flow-through of the QIAamp DNA Blood Mini Kit and in the eluate of a phenol-chloroform isoamyl (PCI) based DNA extraction, to elucidate the DNA losses during extraction. The analyses revealed 2.79-fold higher cfDNA concentrations in unpurified plasma compared to the eluate of the QIAamp DNA Blood Mini Kit, while 36.7% of the total cfDNA were found in the flow-through. The PCI procedure only performed well on samples with high cfDNA concentrations, showing 87.4% of the concentrations measured in plasma. The DNA integrity strongly depended on the sample treatment. Further qualitative analyses indicated differing fractions of cfDNA fragment lengths in the eluate of both extraction methods. In the second module, cfDNA concentrations in the plasma of 74 coronary heart disease patients were compared to cfDNA concentrations of 74 healthy controls, using the direct L1PA2 qPCR for cfDNA quantification. The patient collective showed significantly higher cfDNA levels (mean (SD) 20.1 (23.8) ng/ml; range 5.1-183.0 ng/ml) compared to the healthy controls (9.7 (4.2) ng/ml; range 1.6-23.7 ng/ml). With our direct qPCR, we recommend a simple, economic and sensitive procedure for the quantification of cfDNA concentrations from plasma that might find broad applicability, if cfDNA became an established marker in the assessment of pathophysiological conditions.

Despite their high prevalence, sleep disorders often remain unrecognized and untreated because of barriers to assessment and management. The aims of the present study were to examine associations of complaints of sleep disturbances with cardiovascular disease, related risk factors, and inflammation in the community and to determine the contribution of sleep disturbances to self-perceived physical health.The sample consists of n = 10.000 participants, aged 35 to 74 years of a population based community sample in Germany. Cross-sectional associations of complaints of sleep disturbances with cardiovascular risk factors and disease, biomarkers of inflammation, depression, anxiety, and physical health status were analyzed.19% of our sample endorsed clinically significant sleep disturbances. In the unadjusted analyses severity of sleep disturbances increased with female sex, low socioeconomic status, living without a partnership, cardiovascular disease, depression, anxiety, poor physical health, increased levels of C-reactive protein and fibrinogen. After multivariate adjustment robust associations with coronary heart disease, myocardial infarction and dyslipidemia remained. Complaints of sleep disturbances were strong and independent contributors to self-perceived poor physical health beyond depression, anxiety and medical disease burden.Given the high prevalence of complaints of sleep disturbances and their strong impact on health status, increased efforts should be undertaken for their identification and treatment.

BACKGROUND: Disembodiment is a core feature of depersonalization disorder (DPD). Given the narratives of DPD patients about their disembodiment and emotional numbing and neurobiological findings of an inhibition of insular activity, DPD may be considered as a mental disorder with specific impairments of interoceptive awareness and body perception. METHODS: We investigated cardioceptive accuracy (CA) of DPD patients (n=24) as compared to healthy controls (n=26) with two different heartbeat detection tasks ("Schandry heartbeat counting task" and "Whitehead heartbeat discrimination task"). Self-rated clearness of body perception was measured by questionnaire. RESULTS: Contrary to our hypothesis, DPD patients performed similarly to healthy controls on the two different heartbeat detection tasks, and they had equal scores regarding their self-rated clearness of body perception. There was no correlation of the severity of "anomalous body experiences" and depersonalization with measures of interoceptive accuracy. Only among healthy controls CA in the Schandry task was positively correlated with self-rated clearness of body perception. Depersonalization was unrelated to severity of depression or anxiety, while depression and anxiety were highly correlated. Anxiety and depression did not modify the associations of depersonalization with interoceptive accuracy. CONCLUSIONS: Our main findings highlight a striking discrepancy of normal interoception with overwhelming experiences of disembodiment in DPD. This may reflect difficulties of DPD patients to integrate their visceral and bodily perceptions into a sense of their selves. This problem may be considered an important target for psychotherapeutic treatment approaches.

BACKGROUND: Initial evidence suggests that depressive symptoms are more frequent in patients with atrial fibrillation. Data from the general population are limited. METHODS AND RESULTS: In 10,000 individuals (mean age 56±11 years, 49.4% women) of the population-based Gutenberg Health Study we assessed depression by the Patient Health Questionnaire (PHQ-9) and a history of depression in relation to manifest atrial fibrillation (n = 309 cases). The median (25th/75th percentile) PHQ-9 score of depressive symptoms was 4 (2/6) in atrial fibrillation individuals versus 3 (2/6) individuals without atrial fibrillation, P(X2-Test) = 0.32. Multivariable regression analyses of the severity of depressive symptoms in relation to atrial fibrillation in cardiovascular risk factor adjusted models revealed a relation of PHQ-9 values and atrial fibrillation (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08; P = 0.023). The association was stronger for the somatic symptom dimension of depression (OR 1.08, 95% CI 1.02-1.15; P = 0.0085) than for cognitive symptoms (OR 1.05, 95% CI 0.98-1.11; P = 0.15). Results did not change markedly after additional adjustment for heart failure, partnership status or the inflammatory biomarker C-reactive protein. Both, self-reported physical health status, very good/good versus fair/bad, (OR 0.54, 95% CI 0.41-0.70; P

BACKGROUND: Patients with depersonalization disorder (DPD) typically complain about emotional detachment. Previous studies found reduced autonomic responsiveness to emotional stimuli for DPD patients as compared to patients with anxiety disorders. We aimed to investigate autonomic responsiveness to emotional auditory stimuli of DPD patients as compared to patient controls. Furthermore, we examined the modulatory effect of mindful breathing on these responses as well as on depersonalization intensity. METHODS: 22 DPD patients and 15 patient controls balanced for severity of depression and anxiety, age, sex and education, were compared regarding 1) electrodermal and heart rate data during a resting period, and 2) autonomic responses and cognitive appraisal of standardized acoustic affective stimuli in two conditions (normal listening and mindful breathing). RESULTS: DPD patients rated the emotional sounds as significantly more neutral as compared to patient controls and standardized norm ratings. At the same time, however, they responded more strongly to acoustic emotional stimuli and their electrodermal response pattern was more modulated by valence and arousal as compared to patient controls. Mindful breathing reduced severity of depersonalization in DPD patients and increased the arousal modulation of electrodermal responses in the whole sample. Finally, DPD patients showed an increased electrodermal lability in the rest period as compared to patient controls. CONCLUSIONS: These findings demonstrated that the cognitive evaluation of emotional sounds in DPD patients is disconnected from their autonomic responses to those emotional stimuli. The increased electrodermal lability in DPD may reflect increased introversion and cognitive control of emotional impulses. The findings have important psychotherapeutic implications.

A current model suggested that the somatic symptom dimension accounts for the adverse effect of depression in patients with coronary heart disease (CHD). In order to test this model we sought to determine in a large population-based sample how symptom dimensions of depression are associated with CHD, biomarkers and traditional risk factors. The associations of cognitive and somatic symptom dimensions of depression with CHD, risk factors, endothelial function, and biomarkers of inflammation and myocardial stress were analyzed cross-sectionally in a sample of n = 5000 Mid-Europeans aged 35-74 years from the Gutenberg Health Study (GHS). Only the somatic symptom dimension of depression was associated with CHD, biomarkers (inflammation, vascular function) and cardio-vascular risk factors. When multivariable adjustment was applied by demographic and cardiovascular risk factors, the weak associations of the somatic symptom dimension with the biomarkers disappeared. However, the associations of the somatic symptom dimension with CHD, myocardial infarction, obesity, dyslipidemia and family history of myocardial infarction remained. Both dimensions of depression were independently associated with a previous diagnosis of depression and distressed personality (type D). Thus, our results partly confirm current models: Somatic, but not cognitive-affective symptom dimensions are responsible for the association between depression and CHD, inflammation, vascular function and cardiovascular risk factors in the general population. However, our findings challenge the assumptions that somatic depression might be due to inflammation or vascular dysfunction as consequence of progressed atherosclerotic disease. They rather emphasize a close interplay with life-style factors and with a family history of MI.