Burnout and sick leave due to mental disorders : heritability, comorbidity, risk factors and adverse outcomes

Common mental disorders are an increasing public health problem worldwide, and in Sweden the incidence of sick leave due to stress-related mental disorders has more than doubled since 2010. The aim of this thesis was to explore genetic and environmental aspects of burnout and sick leave due to stress-related and other mental disorders. Data from the population based Swedish Twin Registry’s questionnaire study STAGE (the Study of Twin Adults Genes and Environment) and population registers, including the MiDAS (MicroData for Analyses of the Social insurance) register, were used. Study I was cross-sectional and included 25 378 twins that responded to STAGE. A multivariate biometric twin model was used to assess to what degree the covariation between major depressive disorder, generalized anxiety disorder, and burnout, was explained by common genetic and environmental factors in women and men. A latent common factor explained that the covariation was influenced 58% by genetics and 42% by unique environment. Studies II-III were prospective and contained 23 611 and 11 729 STAGE responders respectively. Information from the MiDAS register was used to follow up for sick leave. In Study II logistic regression with co-twin control and a bivariate twin model was used to assess whether the associations between burnout and sick leave due to stress-related mental disorders, other mental disorders, and somatic conditions, was influenced by familial factors (genetics and shared environment). The phenotypic correlation between burnout and sick leave due to stress-related mental disorders (0.26), and between burnout and sick leave due to other mental disorders (0.30) was explained by genetic factors. The association between burnout and sick leave due to somatic conditions was modest and not influenced by familial factors. In Study III, logistic regression models were used to assess whether psychosocial work environment and health behaviors were risk factors for sick leave due to mental disorders and if the associations were influenced by familial factors. Job strain was a risk factor for sick leave due to mental disorders, after controlling for familial factors, while none of the health behaviors showed independent associations with sick leave due to mental disorders. Study IV was register based and contained 2202 individuals on sick leave due to a mental disorder 2005-2006, according to MiDAS, and their 2202 co-twins. Cox proportional hazards regression models with co-twin control was used to investigate the short and long term effect of sick leave due to mental disorders on the outcomes reoccurring sick leave, disability pension, and unemployment, while taking familial factors into account. The risk of reoccurring sick leave was more than 3 times higher for the first two years of follow up. The risk of disability pension was 12 times higher the first year and remained almost 3 times higher throughout the rest of the follow-up time. The twice as high risk for long-term unemployment was consistent over the up to 8-year follow-up time. In conclusion, burnout shares a genetic vulnerability with depression, anxiety, and sick leave due to mental disorders. Job strain is a risk factor for sick leave due to mental disorders regardless of familial predisposition. Sick leave due to mental disorders is a public health problem that may have serious consequences, both for individuals and to society as a whole

KwaZulu-Natal coastal erosion events of 2006/2007 and 2011: A predictive tool?

Severe coastal erosion occurred along the KwaZulu-Natal coastline between mid-May and November 2011. Analysis of this erosion event and comparison with previous coastal erosion events in 2006/2007 offered the opportunity to extend the understanding of the time and place of coastal erosion strikes. The swells that drove the erosion hotspots of the 2011 erosion season were relatively low (significant wave heights were between 2 m and 4.5 m) but of long duration. Although swell height was important, swell-propagation direction and particularly swell duration played a dominant role in driving the 2011 erosion event. Two erosion hotspot types were noted: sandy beaches underlain by shallow bedrock and thick sandy beaches. The former are triggered by high swells (as in March 2007) and austral winter erosion events (such as in 2006, 2007 and 2011). The latter become evident later in the austral winter erosion cycle. Both types were associated with subtidal shore-normal channels seaward of megacusps, themselves linked to megarip current heads. This 2011 coastal erosion event occurred during a year in which the lunar perigee sub-harmonic cycle (a ±4.4-year cycle) peaked, a pattern which appears to have recurred on the KwaZulu-Natal coast. If this pattern proves true, severe coastal erosion may be expected in 2015. Evidence indicates that coastal erosion is driven by the lunar nodal cycle peak but that adjacent lunar perigee sub-harmonic peaks can also cause severe coastal erosion. Knowing where and when coastal erosion may occur is vital for coastal managers and planners

A multi-country outbreak of Salmonella newport gastroenteritis in Europe associated with watermelon from Brazil, confirmed by whole genome sequencing:October 2011 to January 2012

In November 2011, the presence of Salmonella Newport in a ready-to-eat watermelon slice was confirmed as part of a local food survey in England. In late December 2011, cases of S. Newport were reported in England, Wales, Northern Ireland, Scotland, Ireland and Germany. During the outbreak, 63 confirmed cases of S. Newport were reported across all six countries with isolates indistinguishable by pulsed-field gel electrophoresis from the watermelon isolate. A subset of outbreak isolates were whole-genome sequenced and were identical to, or one single nucleotide polymorphism different from the watermelon isolate. In total, 46 confirmed cases were interviewed of which 27 reported watermelon consumption. Further investigations confirmed the outbreak was linked to the consumption of watermelon imported from Brazil. Although numerous Salmonella outbreaks associated with melons have been reported in the United States and elsewhere, this is the first of its kind in Europe. Expansion of the melon import market from Brazil represents a potential threat for future outbreaks. Whole genome sequencing is rapidly becoming more accessible and can provide a compelling level of evidence of linkage between human cases and sources of infection, to support public health interventions in global food markets

A multi-country outbreak of Salmonella Newport gastroenteritis in Europe associated with watermelon from Brazil, confirmed by whole genome sequencing: October 2011 to January 2012

In November 2011, the presence of Salmonella Newport in a ready-to-eat watermelon slice was confirmed as part of a local food survey in England. In late December 2011, cases of S. Newport were reported in England, Wales, Northern Ireland, Scotland, Ireland and Germany. During the outbreak, 63 confirmed cases of S. Newport were reported across all six countries with isolates indistinguishable by pulsed-field gel electrophoresis from the watermelon isolate. A subset of outbreak isolates were whole-genome sequenced and were identical to, or one single nucleotide polymorphism different from the watermelon isolate. In total, 46 confirmed cases were interviewed of which 27 reported watermelon consumption. Further investigations confirmed the outbreak was linked to the consumption of watermelon imported from Brazil. Although numerous Salmonella outbreaks associated with melons have been reported in the United States and elsewhere, this is the first of its kind in Europe. Expansion of the melon import market from Brazil represents a potential threat for future outbreaks. Whole genome sequencing is rapidly becoming more accessible and can provide a compelling level of evidence of linkage between human cases and sources of infection, to support public health interventions in global food markets

A Comparison of DSM-IV and DSM-5 Panel Members' Financial Associations with Industry: A Pernicious Problem Persists

Lisa Cosgrove and Sheldon Krimsky examine the new competing interest disclosure policy of the American Psychiatric Association (APA) and report that DSM panel members still have considerable financial conflicts of interest

Enriched Environment Increases PCNA and PARP1 Levels in Octopus vulgaris Central Nervous System: First Evidence of Adult Neurogenesis in Lophotrochozoa

Organisms showing a complex and centralized nervous system, such as teleosts, amphibians, reptiles, birds and mammals, and among invertebrates, crustaceans and insects, can adjust their behavior according to the environmental challenges. Proliferation, differentiation, migration, and axonal and dendritic development of newborn neurons take place in brain areas where structural plasticity, involved in learning, memory, and sensory stimuli integration, occurs. Octopus vulgaris has a complex and centralized nervous system, located between the eyes, with a hierarchical organization. It is considered the most "intelligent" invertebrate for its advanced cognitive capabilities, as learning and memory, and its sophisticated behaviors. The experimental data obtained by immunohistochemistry and western blot assay using proliferating cell nuclear antigen and poli (ADP-ribose) polymerase 1 as marker of cell proliferation and synaptogenesis, respectively, revealed cell proliferation in areas of brain involved in learning, memory, and sensory stimuli integration. Furthermore, we showed how enriched environmental conditions affect adult neurogenesis

Immunomodulatory effects of tick saliva on dermal cells exposed to \u3cem\u3eBorrelia burgdorferi\u3c/em\u3e, the agent of Lyme disease

Background: The prolonged feeding process of ixodid ticks, in combination with bacterial transmission, should lead to a robust inflammatory response at the blood-feeding site. Yet, factors present in tick saliva may down-regulate such responses, which may be beneficial to spirochete transmission. The primary goal of this study was to test the hypothesis that tick saliva, in the context of Borrelia burgdorferi, can have widespread effects on the production of immune mediators in skin. Methods: A cross-section of tick feeding on skin was examined histologically. Human THP-1 cells stimulated with B. burgdorferi and grown in the presence or absence of tick saliva were examined by human DNA microarray, cytokine bead array, sandwich ELISA, and qRT-PCR. Similar experiments were also conducted using dermal fibroblasts. Results: Tick feeding on skin showed dermal infiltration of histiocytes and granulocytes at the bite location. Changes in monocytic transcript levels during co-culture with B. burgdorferi and saliva indicated that tick saliva had a suppressive effect on the expression of certain pro-inflammatory mediators, such as IL-8 (CXCL8) and TLR2, but had a stimulatory effect on specific molecules such as the Interleukin 10 receptor, alpha subunit (IL-10RA), a known mediator of the immunosuppressive signal of IL-10. Stimulated cell culture supernatants were analyzed via antigen-capture ELISA and cytokine bead array for inflammatory mediator production. Treatment of monocytes with saliva significantly reduced the expression of several key mediators including IL-6, IL-8 and TNF-alpha. Tick saliva had an opposite effect on dermal fibroblasts. Rather than inhibiting, saliva enhanced production of pro-inflammatory mediators, including IL-8 and IL-6 from these sentinel skin cells. Conclusions: The effects of ixodid tick saliva on resident skin cells is cell type-dependent. The response to both tick and pathogen at the site of feeding favors pathogen transmission, but may not be wholly suppressed by tick saliva

Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = -0.59, p-value = 3.14 × 10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe