Use of metabolomics and proteomics to reveal pathophysiological pathways in anxiety disorders.

With a frequent occurrence of approximately 10.6% in adult populations, anxiety disorders are among the most common mental health problems worldwide. Although anxiety disorders are rather prevalent, their underlying biochemical mechanisms remain unclear. As a functional endpoint of all biological events, the metabolome represents the most precise and direct molecular expression of a phenotype. Combining metabolic information with proteome data, systems biology can draw an even more comprehensive picture of the biological processes. Here, we provide a review summarizing the results from human as well as animal studies analyzing metabolic and proteomic traits in different tissues for associations with anxiety. In addition, we give an overview of animal studies that applied a systems biology approach using metabolic as well as proteomic data to identify anxiety-related pathways

Prospective association between self-reported life satisfaction and mortality: Results from the MONICA/KORA Augsburg S3 survey cohort study.

Background: To identify factors which determine high life satisfaction (LS) and to analyse the prognostic influence of LS on mortality. Methods: Data collection was conducted on 2,675 participants, age 25-74 years, as part of the MONICA Augsburg Project 1994-95. Multivariate logistic regression analyses were used to determine factors associated with high LS (measured with one item, 6-level Likert scale, where "high" = very satisfied/most of the time very satisfied with ones personal life). After 12 years mean follow-up, a total of 245 deaths occurred. We calculated age-and sex-adjusted incident mortality rates per 10,000. Hazard ratios (HRs) were estimated from Cox proportional hazards models. Results: Independent determinants of LS were income, health-perception, and social support, as well as somatisation, anger or depressive symptoms (all p < 0.05). Participants with higher LS (n = 721, 27%) benefited the most with respect to absolute mortality risk reduction (higher LS = 67; mid = 98; low = 140 per 10,000). The sex-stratified analyses indicated an independent association of higher LS and survival for men (HR 0.55; 95% CI 0.37 - 0.81) but not for women.Conclusions: Baseline assessment demonstrated that psychological, social and life-style factors, but not somatic co-morbidities, were relevant determinants of LS. Moreover, the analysis showed that men with higher LS have a substantial long-term survival benefit. The observed association between LS and mortality may be attributed to common underlying causes such as social network integration and/or self-rated health

Distribution and determinants of functioning and disability in aged adults - results from the German KORA-Age study.

Background: Today industrialized countries face a burgeoning aged population. Thus, there is increasing attention on the functioning and disabilities of aged adults as potential determinants of autonomy and independent living. However, there are few representative findings on the prevalence and determinants of disability in aged persons in the German population. The objective of our study is to examine the frequency, distribution and determinants of functioning and disability in aged persons and to assess the contribution of diseases to the prevalence of disability. Methods: Data originate from the MONICA/KORA study, a population-based epidemiological cohort. Survivors of the original cohorts who were 65 and older were examined by telephone interview in 2009. Disability was assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI). Minimal disability was defined as HAQ-DI > 0. Logistic regression was used to adjust for potential confounders and additive regression to estimate the contribution of diseases to disability prevalence. Results: We analyzed a total of 4117 persons (51.2% female) with a mean age of 73.6 years (SD = 6.1). Minimal disability was present in 44.7% of all participants. Adjusted for age and diseases, disability was positively associated with female sex, BMI, low income, marital status, physical inactivity and poor nutritional status, but not with smoking and education. Problems with joint functions and eye diseases contributed most to disability prevalence in all age groups. Conclusions: In conclusion, this study could show that there are vulnerable subgroups of aged adults who should receive increased attention, specifically women, those with low income, those over 80, and persons with joint or eye diseases. Physical activity, obesity and malnutrition were identified as modifiable factors for future targeted interventions

Depression: Ein nach wie vor unterschätztes Risiko für die Entwicklung und Progression der koronaren Herzerkrankung.

Die Bedeutung der Depression als Risikofaktor bei der Entstehung und Progression der koronaren Herzerkrankung (KHK) und mögliche Pathomechanismen sind Gegenstand der vorliegenden Arbeit. Zur Abschätzung der Vorhersage kardiovaskulärer Ereignisse liegen vier Metaanalysen mit ≥100.000 eingeschlossenen Probanden aus Bevölkerungsstudien mit einem adjustierten relativen Risiko von 1.60–1.90 vor. Neben verhaltenswirksamen Effekten (Ernährung, Bewegung, Rauchen, mangelnde Medikamententreue) werden drei zentrale psychobiologische Pathomechanismen diskutiert. Hierzu zählt erstens eine Hyperregulation des autonomen Nervensystems mit erhöhter Herzfrequenzrate, überschießenden Herzfrequenzanstiegen und einer erniedrigten Herzfrequenzvariabilität. Zweitens: überschießende Stressantworten des endokrinen Systems (insbesondere der Hypophysen-Nebennieren-Achse (HPA-Achse) und drittens eine dauerhafte subklinische Erhöhung von Inflammationsparametern (Akute-Phase-Proteine; proinflammatorische Zytokine) mit Veränderungen des Gerinnungssystems (unter anderem durch Thrombozytenaktivierung). Eine anhaltende depressive Symptomatik erhöht auch das Risiko für die Entwicklung der endothelialen Dysfunktion, einer Vorstufe der Atherosklerose. Schließlich spielen gefährliche Nebenwirkungen von Antidepressiva eine Rolle

Impaired sleep predicts cognitive decline in old people: Findings from the prospective KORA Age study.

STUDY OBJECTIVES: To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. METHODS: Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. RESULTS: At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41-2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15-3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. CONCLUSIONS: DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function

Resilience moderates the association between chronic pain and depressive symptoms in the elderly.

BACKGROUND: Chronic pain is frequent in elderly people and, especially if widespread, associated with poor mental health. We investigated whether a resilient personality protects older adults against the adverse effects of chronic pain. METHODS: Pain status [no pain, chronic local pain (CLP) and chronic widespread pain (CWP)] was determined using the American College of Rheumatologists' criteria for widespread pain in a cross-sectional sample of 724 participants aged 68-92 years drawn from the population-based KORA-Age study in Southern Germany. Depressive symptoms and resilience were assessed via the scales GDS-15 and RS-5. The relation between pain, resilience and depressive symptoms was modelled using logistic and quantile regression. RESULTS: CLP prevalence and CWP prevalence were 57.5% and 12.3%, respectively. Confounder-adjusted logistic regression indicated a fourfold risk of depressed mood (GDS-15 ≥ 5) in CWP, vs. no pain (OR = 4.08, 95% CI 1.90-8.74). However, in quantile regression, the adverse effect of CWP was significantly attenuated by resilience when looking at the GDS-15 score lower quartile (p = 0.011) and median (p = 0.011). This effect appeared to be mainly driven by participants aged 75-84 years. Confounder adjustment reduced the effect of CLP on depressive symptoms to non-significance, and effect modification by resilience was undetectable in regression models of CLP. CONCLUSIONS: Resilience was protective in the association of CWP with depressive symptoms in this analysis. Older adults with CWP may potentially benefit from interventions supporting resilience. Prospective research should investigate the protective role of resilience in the potentially self-perpetuating relation between chronic pain and depressed affect. WHAT DOES THIS STUDY ADD?: The association of chronic widespread pain with depressive symptoms in the elderly population is attenuated by resilience

Clustering of negative affectivity and social inhibition in the community: Prevalence of type D personality as a cardiovascular risk marker.

OBJECTIVE: To explore the prevalence of Type D personality-the combination of negative affectivity and social inhibition-in the general population and its relationship to other cardiovascular risk factors, including psychopathological symptoms. Type D personality has been identified as a prognostic risk factor for various cardiovascular disease conditions. METHODS: In a representative sample of 2698 individuals (aged 35-74 years), psychological, lifestyle, and somatic risk factors were investigated with laboratory testing, self-report measures, and a clinical interview. Type D was assessed with the German Type D Scale-14. RESULTS: The prevalence of Type D was 23.4% (95% confidence interval [CI], 21.2-25.6) in men and 26.9% (95% CI, 23.7-30.1) in women and, thus, in the range of classical risk factors (e.g., hypercholesterolemia). In age-adjusted analysis, Type D was associated with psychopathological symptoms, including depression and somatic symptom burden. With the exception of physical inactivity in both sexes, hypertension in women and hypercholesterolemia in men, Type D was not associated with classical cardiovascular risk factors. Multivariate analysis revealed depression, exhaustion, anxiety, and low self-rated health as associated with Type D in both sexes (odds ratios, 1.97-3.21 in men, 1.52-2.44 in women). CONCLUSIONS: A Type D personality disposition can be found in about a quarter of the general population, which is comparable to the prevalence of classical cardiovascular risk factors. In both sexes, an independent association to Type D appeared mainly in psychopathological symptoms. Type D constitutes a relevant and independent risk marker in the community and should receive attention in clinical practice

Mid-life job insecurity associated with subjective well-being in old age: Results from the population-based MONICA/KORA study.

OBJECTIVE: This study aimed to examine prospectively the influence of exposure to job insecurity during working life on subjective well-being (SWB) after retirement, an association which has not been studied to date. METHOD: Data were derived from the prospective population-based MONICA/KORA study conducted in southern Germany. Participants were recruited and data were collected during three independent surveys between 1984-1995 (T1) and followed up in 2009 (T2). The study sample consisted of 1801 employed participants (1146 male/ 655 female) aged 41-72 years at T1 and ≥65 years at T2, without missing data. Self-administered questionnaires and clinical examinations were used to assess job insecurity and risk factors at T1 and SWB at T2. Mean follow-up was 19.6 years. Logistic regression analyses were performed to determine the association of job insecurity with SWB after retirement. We accounted for an extensive set of sociodemographic, lifestyle-, health- and work-related risk factors. RESULTS: At T1, 39.5% of the participants reported job insecurity, which was associated with a 1.40-fold [95% confidence interval (95% CI) 1.08-1.82] risk of low SWB at T2 in models adjusted for sociodemographic and lifestyle- and health-related conditions at T1. Additional adjustment for a set of work-related risk factors at T1 had little effect on this association. CONCLUSIONS: Exposure to job insecurity at midlife was associated with low SWB in retirement, even after controlling for an extensive set of risk factors. This shows that the negative effects of unstable working conditions might persist well into retirement, long after cessation of employment

Metallothionein differentially affects the host response to Listeria infection both with and without an additional stress from cold-restraint.

Acute stress alters anti-bacterial defenses, but the neuroimmunological mechanisms underlying this association are not yet well understood. Metallothionein (MT), a cysteine-rich protein, is a stress response protein that is induced by a variety of chemical, biological, and psychological stressors, and MT has been shown to influence immune activities. We investigated MT’s role in the management of anti-bacterial responses that occur during stress, using a C57BL/6 (B6) strain that has targeted disruptions of the Mt1 and Mt2 genes (B6-MTKO), and a B6 strain that has additional copies of Mt (B6-MTTGN). The well-characterized listeriosis model was used to examine immune mechanisms that are altered by a 1-h stress treatment (cold-restraint, CR) administered just prior to bacterial infection. Intriguingly, MT gene doses both greater and lower than that of wild-type (WT) B6 mice were associated with improved host defenses against Listeria monocytogenes (LM). This augmented protection was diminished by CR stress in the MTKO mice, but transgenic mice with additional MT copies had no CR stress-induced increase in their listerial burden. During the transition from innate to adaptive immunity, on day 3 after infection, oxidative burst and apoptosis were assessed by flow cytometric methods, and cytokine transcription was measured by real-time quantitative PCR. MT gene expression and CR-stress affected the expression of IL-6 and TNFα. Additionally, these genetic and environmental modulations altered the generation of ROS responses as well as the number of apoptotic cells in livers and spleens. Although the level of MT altered the listerial response, MT expression was equally elevated by listerial infection with or without CR stress. These results indicate the ability of MT to regulate immune response mechanisms and demonstrate that increased amounts of MT can eliminate the immunosuppression induced by CR

Sex-related differences in the association of salivary cortisol levels and type 2 diabetes. Findings from the cross-sectional population based KORA-Age study.

BACKGROUND: Dysregulation in the cortisol secretion may have a role in the development of type 2 diabetes although conflicting evidence on the particular cortisol secretion patterns and type 2 diabetes demands further investigations. We aim to examine the association of cortisol levels and diurnal secretion patterns with prevalence of type 2 diabetes and HbA1c levels as well as the potential impact of sex and adiposity on this association. METHODS: A cross-sectional analysis was conducted among 757 participants (aged 65-90 years) of the population-based KORA (Cooperative Health Research in the Region of Augsburg)-Age study. Multivariate regression analyses were employed to examine the association between salivary cortisol (measured upon waking (M1), 30min after awakening (M2), and in the late night (LNSC)) and type 2 diabetes as well as glycated hemoglobin (HbA1c) with adjustments for potential confounders. RESULTS: In the total sample population, an elevated LNSC level was observed in type 2 diabetes patients compared to non-patients (P=0.04). In sex-stratified analyses, diabetic men showed a greater Cortisol Awakening Response (CAR) (P=0.02). Diabetic women had significantly elevated LNSC levels (P=0.04). HbA1c was positively associated with both CAR and LNSC levels but was negatively associated with M1 to LNSC ratio. CONCLUSION: In this aged population, type 2 diabetes is associated with dysregulated cortisol secretion characterized by distinct sex specific diurnal patterns