Cigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and ...smoking-related diseases. We performed a meta-analysis of transcriptome-wide gene expression using whole blood-derived RNA from 10,233 participants of European ancestry in six cohorts (including 1421 current and 3955 former smokers) to identify associations between smoking and altered gene expression levels. At a false discovery rate (FDR) <0.1, we identified 1270 differentially expressed genes in current vs. never smokers, and 39 genes in former vs. never smokers. Expression levels of 12 genes remained elevated up to 30 years after smoking cessation, suggesting that the molecular consequence of smoking may persist for decades. Gene ontology analysis revealed enrichment of smoking-related genes for activation of platelets and lymphocytes, immune response, and apoptosis. Many of the top smoking-related differentially expressed genes, including LRRN3 and GPR15, have DNA methylation loci in promoter regions that were recently reported to be hypomethylated among smokers. By linking differential gene expression with smoking-related disease phenotypes, we demonstrated that stroke and pulmonary function show enrichment for smoking-related gene expression signatures. Mediation analysis revealed the expression of several genes (e.g. ALAS2) to be putative mediators of the associations between smoking and inflammatory biomarkers (IL6 and C-reactive protein levels). Our transcriptomic study provides potential insights into the effects of cigarette smoking on gene expression in whole blood and their relations to smoking-related diseases. The results of such analyses may highlight attractive targets for treating or preventing smoking-related health effects.
In Germany, large, population-based cohort studies have been implemented in order to identify risk and protective factors for maintaining health across the life span. The purpose of this systematic ...review is to analyse findings from three large ongoing cohorts and to identify sex-specific prevalence rates, risk and protective factors for mental health. Published studies from the Cooperative Health Research in the Region Augsburg (KORA), the Study of Health in Pomerania (SHIP) and the Gutenberg Health Study (GHS)), representing the southern, north-eastern and middle parts of Germany, were identified through searches of the databases PubMed and Web of Science. A total of 52 articles was identified from the start of each cohort until June 2019. Articles reporting prevalence rates of mental health
= 22, explanatory factors for mental health
= 25, or both
= 5 were identified. Consistent across cohorts, higher prevalence rates of internalizing disorders were found for women and more externalizing disorders for men. Risk and protective factors for mental health included social factors, lifestyle, physical health, body mass index (BMI), diabetes, genetic and biological factors. In all areas, differences and similarities were found between women and men. The most evident were the sex-specific risk profiles for depression with mostly external risk factors for men and internal risk factors for women. Gender was not assessed directly, therefore we examined whether socioeconomic and family-related factors reflecting gender roles or institutionalized gender could be used as a proxy for gender. Overall, this systematic review shows differences and similarities in prevalence rates and determinants of mental health indicators between women and men. They underline the importance of focussing on sex specific approaches in mental health research and in the development of prevention measures. Current research on mental health still lacks focus on gender aspects. Therefore, an increased focus on sex and gender in mental health research is of great importance.
This review paper explores the potential psychiatric and psychological sequelae of vaccine-induced immune thrombotic thrombocytopenia, also called vaccine-induced immune thrombocytopenia, and ...thrombosis (VITT). In the absence of any literature to date we have extrapolated data from similar conditions, particularly data pertaining to the critical care population. We discuss both the direct and indirect effects of thrombosis, likely psychiatric and psychological challenges during recovery, and ethical issues around vaccination. We have also suggested a comprehensive guide to the psychiatric assessment and management of patients presenting with VITT with the aim of early identification of problems and maximizing rehabilitation potential and quality of life.
OBJECTIVETo investigate the association of enlarged perivascular spaces (ePVS) with cognition in elderly without dementia.
METHODSWe included 5 studies from the Uniform Neuro-Imaging of Virchow-Robin ...Space Enlargement (UNIVRSE) consortium, namely the Austrian Stroke Prevention Family Study, Study of Health in Pomerania, Rotterdam Study, Epidemiology of Dementia in Singapore study, and Risk Index for Subclinical Brain Lesions in Hong Kong study. ePVS were counted in 4 regions (mesencephalon, hippocampus, basal ganglia, and centrum semiovale) with harmonized rating across studies. Mini-Mental State Examination (MMSE) and general fluid cognitive ability factor (G-factor) were used to assess cognitive function. For each study, a linear regression model was performed to estimate the effect of ePVS on MMSE and G-factor. Estimates were pooled across studies with the use of inverse variance meta-analysis with fixed- or random-effect models when appropriate.
RESULTSThe final sample size consisted of 3,575 persons (age range 63.4–73.2 years, 50.6% women). Total ePVS counts were not significantly associated with MMSE score (mean difference per ePVS score increase 0.001, 95% confidence interval CI −0.007 to 0.008, p = 0.885) or G-factor (mean difference per ePVS score increase 0.002, 95% CI −0.001 to 0.006, p = 0.148) in age-, sex-, and education-adjusted models. Adjustments for cardiovascular risk factors and MRI markers did not change the results. Repeating the analyses with region-specific ePVS rendered similar results.
CONCLUSIONSIn this study, we found that ePVS counts were not associated with cognitive dysfunction in the general population. Future studies with longitudinal designs are warranted to examine whether ePVS contribute to cognitive decline.
To identify und support particular target groups for mental health prevention, we explore the links between shame and help-seeking intentions concerning mental health in different lifestyles (based ...on socioeconomic status as well as health-related behaviors). Lifestyles were operationalized by nine confirmatory, homogenous clusters of the sample. These clusters are based on individuals' similarities in sociodemographic aspects and health behavior. Analyses included t tests, Chi-square, ANOVA, regressions investigating in sociodemographic characteristics. Hierarchical linear models examining cross-sectional associations of shame and willingness to seek help for different lifestyles of participants of the Study of Health in Pomerania (SHIP-START-1 and SHIP-START-3, data collected 2002-2006 and 2014-2016; n = 1630). Hierarchical linear models showed small context effects for lifestyle-related associations of shame and willingness to seek help. For younger as well as male participants, lifestyles indicated different associations of shame and help-seeking intentions: Especially the lifestyles with unhealthy behaviors and high as well as low socioeconomic status resulted in higher shame being associated with low help-seeking intentions in case of mental illness. Lifestyle clusters might be a useful tool to identify marginalized groups with unhealthy behaviors, which should be addressed by interventions and prevention programs.
Previous studies suggested that exposure to traumatic events during childhood and adulthood and post-traumatic stress disorder (PTSD) are associated with a dysregulation of different neuroendocrine ...systems. However, the activity of the renin-angiotensin-aldosterone-system (RAAS) in relation to trauma/PTSD has been largely neglected.
Traumatization, PTSD, and plasma concentrations of renin and aldosterone were measured in 3092 individuals from the general population. Subgroups according to the status of traumatization ('without trauma'; 'trauma, without PTSD', 'PTSD') were formed and compared regarding renin and aldosterone concentrations. Additionally, we calculated the associations between the number of traumata, renin, and aldosterone concentrations. Finally, associations of PTSD with renin/aldosterone levels were controlled for the number of traumata ('trauma load').
Levels of renin, but not aldosterone, were increased in traumatized persons without PTSD (p = 0.02) and, even stronger, with PTSD (p < 0.01). Moreover, we found a dose-response relation between the number of traumata and renin levels (β = 0.065; p < 0.001). Regression analyses showed PTSD as a significant predictor of renin (β = 0.38; p < 0.01). This effect was only slightly attenuated when controlled for trauma load (β = 0.32; p < 0.01).
Our results suggest that traumatization has lasting and cumulative effects on RAAS activity. Finding elevated renin levels in PTSD independent from trauma load supports the concept of PTSD as a disorder with specific neuroendocrine characteristics. Alternatively, elevated renin levels in traumatized persons may increase the risk for developing PTSD. Our findings contribute to explain the relationship between traumatic stress/PTSD and physical disorders.
To investigate the role of epigenetics in statins' diabetogenic effect comparing DNA methylation (DNAm) between statin users and nonusers in an epigenome-wide association study in blood.
Five cohort ...studies' participants (
= 8,270) were classified as statin users when they were on statin therapy at the time of DNAm assessment with Illumina 450K or EPIC array or noncurrent users otherwise. Associations of DNAm with various outcomes like incident type 2 diabetes, plasma glucose, insulin, and insulin resistance (HOMA of insulin resistance HOMA-IR) as well as with gene expression were investigated.
Discovery (
= 6,820) and replication (
= 1,450) phases associated five DNAm sites with statin use: cg17901584 (1.12 × 10
), cg10177197 (3.94 × 10
), cg06500161 (2.67 × 10
), cg27243685 (6.01 × 10
), and cg05119988 (7.26 × 10
). Two sites were associated with at least one glycemic trait or type 2 diabetes. Higher cg06500161 methylation was associated with higher fasting glucose, insulin, HOMA-IR, and type 2 diabetes (odds ratio 1.34 95% CI 1.22, 1.47). Mediation analyses suggested that
methylation partially mediates the effect of statins on high insulin and HOMA-IR. Gene expression analyses showed that statin exposure and
methylation were associated with
downregulation, suggesting epigenetic regulation of
expression. Further, outcomes insulin and HOMA-IR were significantly associated with
expression.
This study sheds light on potential mechanisms linking statins with type 2 diabetes risk, providing evidence on DNAm partially mediating statins' effects on insulin traits. Further efforts shall disentangle the molecular mechanisms through which statins may induce DNAm changes, potentially leading to
epigenetic regulation.
Context:
Measurement of IGF-binding protein-3 (IGFBP-3) can aid the diagnosis of GH-related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I to IGFBP-3 ratio ...are associated with clinical end points like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals.
Objective:
The objective of the study was the establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I to IGFBP-3 ratio by newly developed automated immunoassays.
Setting:
This was a multicenter study with samples from 11 cohorts from the United States, Canada, and Europe.
Participants:
A total of 14 970 healthy subjects covering all ages from birth to senescence participated in the study.
Main Outcome Measures:
Concentrations of IGFBP-3 and the IGF-I to IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays were measured.
Results:
Both the concentration of IGFBP-3 and the IGF-I to IGFBP-3 ratio are mainly determined by age. IGFBP-3 concentrations increase until the age of 22 years, with a plateau being visible between 15 and 25 years. Determined by the high peripubertal peak in IGF-I, the peak in the IGF-I to IGFBP-3 ratio occurs already around the age of 15 years, with a slightly earlier and higher peak in females. Beyond the age of 60 years, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I to IGFBP-3 ratio remains significantly higher in males.
Conclusions:
We present an extensive set of assay-specific age- and sex-adjusted normative data for concentrations of IGFBP-3 and the molar IGF-I to IGFBP-3 ratio and demonstrate distinct sex specific differences across the life span.
White matter lesions (WML) emerge as a consequence of vascular injuries in the brain. While they are commonly observed in aging, associations have been established with neurodegenerative and ...neurological disorders such as dementia or stroke. Despite substantial research efforts, biological mechanisms are incomplete and biomarkers indicating WMLs are lacking. Utilizing data from the population-based
(SHIP), our objective was to identify plasma-circulating micro-RNAs (miRNAs) associated with WMLs, thus providing a foundation for a comprehensive biological model and further research. In linear regression models, direct association and moderating factors were analyzed. In 648 individuals, we identified
-miR-425-5p as directly associated with WMLs. In subsequent analyses,
-miR-425-5p was found to regulate various genes associated with WMLs with particular emphasis on the
gene. Furthermore, miR-425-5p was found to be involved in immunological processes. In addition, noteworthy miRNAs associated with WMLs were identified, primarily moderated by the factors of sex or smoking status. All identified miRNAs exhibited a strong over-representation in neurodegenerative and neurological diseases. We introduced
-miR-425-5p as a promising candidate in WML research probably involved in immunological processes. Mir-425-5p holds the potential as a biomarker of WMLs, shedding light on potential mechanisms and pathways in vascular dementia.
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