Interaction between the BDNF gene rs16917237 polymorphism and job stress on job burnout of Chinese university teachers.

BACKGROUND: Job burnout is related to both environmental and genetic factors. However, previous studies on job burnout in teachers have mainly focused on potential stressors in the environment, while ignoring genetic factors. Brain-derived neurotrophic factor (BNDF) may be a pathogenic factor involved in burnout symptoms. Therefore, this study further investigated the relationship between the BNDF gene polymorphism, job stress and job burnout in Chinese university teachers. METHODS: Using a cross-sectional design, 361 faculty and staff members from a university in Beijing were enrolled. Job stress was measured with the Work Stress Scale. Job burnout was measured by the Chinese version of the Maslach Burnout Inventory which has three dimensions, namely emotional exhaustion (EE), cynicism (CY), and reduced personal accomplishment (PA). The BDNF gene rs16917237 polymorphism was genotyped in all participants. RESULTS: CY score was associated with education level (p < 0.01), and PA score was associated with age (p < 0.05). Job stress was positively correlated with EE (r = 0.776), CY (r = 0.457), and PA (r = 0.163) (all p < 0.01). After controlling for gender, age and education level, the BDNF gene rs16917237 polymorphism did not affect job burnout, but it interacted with job stress to influence EE and CY (both p < 0.05), indicating that individuals with TT genotype were more susceptible to higher levels of job stress, resulting in job burnout symptoms. CONCLUSIONS: Our results suggest that the BDNF gene rs16917237 TT genotype may be a risk factor for job burnout in Chinese university teachers.

The prevalence of nurse burnout and its association with telomere length pre and during the COVID-19 pandemic.

BACKGROUND: Burnout is a work-related stress syndrome characterized by emotional exhaustion, depersonalization, and reduced personal accomplishment. Nurse burnout is related to nurses' deteriorating mental health and poorer patient care quality and thus, is a significant concern in healthcare. The Coronavirus Disease 2019 (COVID-19) pandemic has swept the world and distressed the healthcare systems. Because of the body's stress mechanism, it is vital to examine the current prevalence of nurse burnout and understand it at a biological level, using an epigenetic biomarker, telomere length. PURPOSE: To determine the prevalence of burnout among nurses in the Peri-Operative and Labor & Delivery settings pre and during the COVID-19 pandemic and to examine the effects of burnout on absolute telomere length. METHODS: This is a cross-sectional study assessing the prevalence of nurses' burnout and the relationships between nurses' burnout and telomere length. Due to the COVID-19 pandemic, we had to stop the study during the mid of data collection. Even though the study was not designed to capture changes before and during the pandemic, we analyzed two groups' data before and during the pandemic. The study took place in a US hospital. Nurses in the hospital's Operating Room, Post-Anesthesia Care Unit, and Labor & Delivery Unit participated in the study. Maslach Burnout Inventory survey and nurses' demographics were administered online. Telomere length was measured via finger-prick blood. RESULTS: 146 nurses participated in the study, with 120 participants' blood samples collected. The high-level burnout rate was 70.5%. Correlation analysis did not reveal a direct correlation between nurse burnout and telomere length. However, in a multiple regression analysis, the final model contained the burnout subscale of emotional exhaustion, years as an RN, and work unit's nursing care quality. There was a low degree of departure from normality of the mean absolute telomere length in the pre-pandemic group and a substantial degree of departure in the during-pandemic group. CONCLUSIONS: Nurse burnout is a prevalent phenomenon in healthcare, and this study indicates that nurses currently experience high levels of burnout. Nurses' cellular biomarker, telomere length, is shorter in the group of nurses during the COVID-19 pandemic than before. Appropriate measures should be implemented to decrease nurses' burnout symptoms and improve nurses' psychological and physical health. Nurses, especially those younger than 60, report higher burnout symptoms, particularly emotional exhaustion. This study indicates the need for intervention to promote nurses' health during the pandemic and beyond. If not appropriately managed, nurse burnout may continue to be a significant issue facing the healthcare system.

The relationship between occupational stress and job burnout in coal miners: Interactions between GCCR and SLC6A4 gene polymorphisms and the environment.

OBJECTIVE: To understand the current situation of job burnout among coal miners in Xinjian. The effects of occupational stress, GCCR and SLC6A4 gene polymorphisms, and gene-environment interactions on job burnout in coal miners were analyzed. This study provides a scientific basis for formulating health strategies to combat job burnout in the future. METHODS: The job burnout scale and job content questionnaire (JCQ) were used to investigate the general situation of job burnout among coal miners and its influencing factors. The imLDRTM multiple SNP typing kit was used to type 300 samples (150 samples from the burnout case group and 150 from the control group). The relationship between the occurrence of job burnout, and the GCCR and SLC6A4 genes was analyzed. RESULTS: There were significant differences in the rate of burnout among miners of different sexes, ages, working years, shifts, working types, and marital status (P < 0.05). The difference in occupational stress between the different job burnout groups was statistically significant (P < 0.05). The GG genotype at rs41423247 increased the risk of burnout (OR=3.224, 95% CI:1.425-7.294). Similarly, compared to the TT genotype at rs11080122, the CC genotype increased the susceptibility of job burnout (OR =2.614, 95% CI:1.047-6.527). The results of gene-environment interaction regression analyses showed that the interaction between rs41423247, rs17209237, and occupational stress increased the risk of job burnout (OR = 5.049, 95% CI = 2.371-10.750). CONCLUSION: In addition to demographic characteristics, occupational stress was also a risk factor for job burnout. The interaction between rs41423247 and rs17209237 of the GCCR gene and occupational stress increased the risk of job burnout.

The relationship between job stress and job burnout moderated by BDNF rs6265 polymorphism.

RATIONALE: Job stress can lead to job burnout, and BDNF polymorphism has been found to be involved in its psychopathological mechanism. Research needs a better understanding of the important role of gene × environment (i.e., BDNF polymorphism × job stress) interaction on job burnout. OBJECTIVE: This study aimed to explore how BDNF rs6265 polymorphism may moderate the relationship between job stress and job burnout. METHODS: Three hundred forty-one healthy participants (187 males and 154 females) from a Chinese university were included. The present study used a standardized questionnaire including demographic characteristics, job stress assessed by the House and Rizzo's Work Stress Scale, and job burnout assessed by the Maslach Burnout Inventory-General Survey. The BDNF rs6265 polymorphism was genotyped. RESULTS: Job stress showed a positive correlation with emotional exhaustion (p < 0.001), cynicism (p < 0.001), and reduced personal accomplishment (p < 0.01). The main effects of BDNF rs6265 polymorphism on emotional exhaustion and cynicism were significant [F(1,333) = 5.136, p = 0.024; F(1,333) = 4.175, p = 0.042, respectively]. The interaction between job stress and BDNF rs6265 on cynicism was significant (△ R2 = 0.013, p = 0.014) after controlling for age, sex, education, and position, indicating that individuals with BDNF rs6265 TT genotype showed higher level of cynicism when in high job stress. CONCLUSIONS: The results provided evidence for the association of BDNF gene rs6265 polymorphism, job stress, and their interaction with job burnout. Individuals with TT genotype in BDNF rs6265 might be susceptible to stressful situations, which would lead to cynicism.

Burnout in university faculty: An interaction between subjective sleep quality and the OXTR rs2268498 polymorphism.

BACKGROUND: Job burnout is a stress-related syndrome influenced by both genetic and environmental factors. Poor sleep quality acting as a stressor may lead to job burnout. The oxytocin receptor gene (OXTR) related to stress reactivity may also exert an effect on job burnout. We aimed to explore the effect of sleep quality, a functional OXTR rs2268498 polymorphism, and their interaction on job burnout in the Chinese population, which has not been explored yet. METHODS: A preliminary study was performed using a cross-sectional design. The Pittsburgh Sleep Quality Index (PSQI) and the Malash Burnout Inventory (MBI) were measured from 575 healthy subjects. The OXTR rs2468498 polymorphism was genotyped in 376 subjects. RESULTS: There were significant main effects of sleep quality (p<0.05), but not of the OXTR rs2468498 genotype on burnout. Interestingly, the interaction between sleep quality and the rs2468498 genotype was significant (p<0.05). In the poor sleep group, the C allele (C/C and T/C) carriers showed higher Emotional Exhaustion level than T homozygotes, while in the good sleep group, the C allele carrier showed a lower Emotional Exhaustion level. LIMITATIONS: This study covered subjects from only one university and the sample size for genotyping was relatively small. As we analyzed only the OXTR rs2268498 polymorphism, this study could not reveal the effects of the cerebrospinal oxytocin concentration and the haplotypes. CONCLUSIONS: Our findings suggest that the OXTR polymorphism modulates the influence of subjective sleep quality on burnout. We conclude that the C allele of the OXTR rs2468498 polymorphism plays a susceptible role in job burnout.

Interaction between job stress, serum BDNF level and the BDNF rs2049046 polymorphism in job burnout.

BACKGROUND: Some studies have shown that long-term exposure to job stress could result in burnout, and BDNF polymorphism may play an important role in its psychopathological mechanism. However, the inter-relationships between the job-related stress, serum BDNF level, BDNF genotype and job burnout have not been examined. This study was to explore the job stress × BDNF rs2049046 interaction and the role of serum BDNF level in job burnout in a Chinese Han population. METHODS: Using a cross-sectional design, 205 healthy subjects were recruited from a public institution in Beijing and assessed for job stress using the House and Rizzo's Work Stress Scale, and job burnout using the Maslach Burnout Inventory (MBI). The BDNF rs2049046 polymorphism was genotyped and serum BDNF (sBDNF) levels were assayed in all of subjects. RESULTS: The correlations between the job stress score and two burnout subscale scores (emotional exhaustion and cynicism) were significant (both p < 0.001), but not with professional efficacy. There were no significant main effects of the BDNF rs2049046 genotype on burnout, and no significant correlation was observed between sBDNF levels and job burnout. However, the interaction between the job stress and the BDNF rs2049046 genotype (F = 2.709, df = 2, 183, p = 0.032) or between the job stress and sBDNF levels on burnout was significant (t = -2.132, p = 0.035). To be specific, the individuals with the BDNF rs2049046 AT genotype showed a greater susceptibility to the burnout cynicism compared to AA homozygote only in medium-stress group (F = 4.327, df = 1,117, p = 0.015). The individuals who had lower sBDNF showed higher burnout level than those who had higher sBDNF in low-stress group. CONCLUSIONS: Our findings suggest that the BDNF system may interact with job stress to affect burnout, showing that interaction between BDNF rs2049046 and job stress or the interaction between BDNF levels with work stress on certain burnout dimensions.

Interactive effects of corticotropin-releasing hormone receptor 1 gene and work stress on burnout in medical professionals in a Chinese Han population.

BACKGROUND: Burnout is a worked-related stress syndrome caused by long-term exposure to a stressful environment. Dysregulation of the hypothalamic- pituitary- adrenal (HPA) axis may be involved in both stress and burnout; an evaluation of genetic polymorphisms which alter activity in the HPA may be predictive of how likely an environment is to produce burnout. METHODS: Using a cross-sectional design, this study examined whether corticotrophin-releasing hormone receptor 1 (CRHR1) gene polymorphism rs110402 is a risk factor for burnout; further, it explores whether the interaction of stress × CRHR1 gene predicts burnout in the healthcare workers in a Chinese Han population. House and Rizzo's work stress scale, Sources of Pressure Scale and Maslach Burnout Inventory-General Survey were administered to 712 participants from a large general hospital in Beijing. The CRHR1 rs110402 polymorphism was genotyped in 376 participants. RESULTS: Our results showed significant positive inter-correlations between stressor, work stress and depressive scores (all p < 0.001) with only one exception. Males, younger age and higher educational level were associated with burnout (all p < 0.05). The presence of the CRHR1 rs110402 genotype was not correlated with the presence of job stress or burnout. However, we found statistically significant interaction between CRHR1 rs110402 and job stress on burnout (p < 0.05). Individuals homozygous for the A allele reported significantly higher emotional exhaustion than G allele carriers in the high stress group. LIMITATIONS: The sample was only chosen from the medical professions, and the sample size was relatively small. Only one polymorphism in CRHR1 gene was analyzed, while only about half of the total individuals were genotyped. CONCLUSIONS: Our results suggest a close relationship between work-related stress and burnout and that the A allele of the CRHR1 rs110402 polymorphism may enhance feelings of emotional exhaustion when experiencing work-related stress.

Serotonin transporter gene (5-HTT) rs6354 polymorphism, job-related stress, and their interaction in burnout in healthcare workers in a Chinese hospital.

OBJECTIVE: Many studies have reported that long-term exposure to job-related stress can lead to burnout, which may be influenced by genetic and environmental factors. Burnout correlates with depression. This study investigated whether one tag polymorphism rs6354 in 5-HTT gene modulated the influence of job-related stress on burnout in the medical professionals in a Chinese Han population, which to our best knowledge has not been explored. METHODS: Seven hundred twelve subjects were recruited from a general hospital and measured for burnout symptoms using the Maslach Burnout Inventory (MBI), the stress using the House and Rizzo's Work Stress Scale, and the stressors using the Evers, Frese, and Cooper's Sources of Pressure Scale. The 5-HTT rs6354 polymorphism was genotyped in 376 subjects. RESULTS: The majority of correlations between the work stress score or the six stressor scores and three burnout subscores were significant (all p < 0.05). There was no significant main effect of the 5-HTT rs6354 genotype on burnout symptoms; however, there was a statistically significant interaction between 5-HTT rs6354 and work stress on burnout (F = 5.08, df = 2, 369, p = 0.007). In the low stress group, G allele carriers had significantly higher burnout level than TT homozygote (F = 11.60, df = 1, 48, p < 0.001). On the contrary, in the high stress group, G allele carriers exhibited significantly lower burnout level compared to TT homozygote (F = 3.86, df = 1, 103, p = 0.025). CONCLUSIONS: Our findings suggest that the 5-HTT rs6354 polymorphism may modulate the influence of job-related stress on burnout by adjusting serotonin transporter function and neurotransmission, showing that individuals with TT genotype displayed a greater susceptibility to both the detrimental effects of higher stress and the beneficial effects of lower stress compared to those with G allele, which supports the differential-susceptibility hypothesis.

Stress, burnout and depression: A systematic review on DNA methylation mechanisms.

Despite that burnout presents a serious burden for modern society, there are no diagnostic criteria. Additional difficulty is the differential diagnosis with depression. Consequently, there is a need to dispose of a burnout biomarker. Epigenetic studies suggest that DNA methylation is a possible mediator linking individual response to stress and psychopathology and could be considered as a potential biomarker of stress-related mental disorders. Thus, the aim of this review is to provide an overview of DNA methylation mechanisms in stress, burnout and depression. In addition to state-of-the-art overview, the goal of this review is to provide a scientific base for burnout biomarker research. We performed a systematic literature search and identified 25 pertinent articles. Among these, 15 focused on depression, 7 on chronic stress and only 3 on work stress/burnout. Three epigenome-wide studies were identified and the majority of studies used the candidate-gene approach, assessing 12 different genes. The glucocorticoid receptor gene (NR3C1) displayed different methylation patterns in chronic stress and depression. The serotonin transporter gene (SLC6A4) methylation was similarly affected in stress, depression and burnout. Work-related stress and depressive symptoms were associated with different methylation patterns of the brain derived neurotrophic factor gene (BDNF) in the same human sample. The tyrosine hydroxylase (TH) methylation was correlated with work stress in a single study. Additional, thoroughly designed longitudinal studies are necessary for revealing the cause-effect relationship of work stress, epigenetics and burnout, including its overlap with depression.

An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

Genetic and environmental influences on the association between performance-based self-esteem and exhaustion: A study of the self-worth notion of burnout.

In the self-worth model, burnout is considered to be a syndrome of performance-based self-esteem (PBSE) and experiences of exhaustion. Studies have shown that PBSE and burnout indices such as Pines' Burnout Measure (BM) are associated. Whether these variables have overlapping etiologies has however not been studied before. Genetic and environmental components of covariation between PBSE and exhaustion measured with Pines' BM were examined in a bivariate Cholesky model using data from 14,875 monozygotic and dizygotic Swedish twins. Fifty-two per cent of the phenotypic correlation (r = 0.41) between PBSE and Pines' BM was explained by genetics and 48% by environmental factors. The findings of the present study strengthen the assumption that PBSE should be considered in the burnout process as proposed by the self-worth conception of burnout. The present results extend our understanding of the link between this contingent self-esteem construct and exhaustion and provide additional information about the underlying mechanisms in terms of genetics and environment. This finding corroborates the assumed syndrome view on burnout, while it also suggests an altered view of how the syndrome emerges and how it can be alleviated.

Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

The covariation between burnout and sick leave due to mental disorders is explained by a shared genetic liability: a prospective swedish twin study with a five-year follow-up.

BACKGROUND: This study aims to assess whether the associations between burnout and sick leave due to stress-related mental disorders, other mental disorders, and somatic conditions are influenced by familial (genetic and shared environmental) factors. METHODS: In this prospective cohort study, 23,611 Swedish twins born between 1959 and 1985, who answered a web-based questionnaire, including the Pines Burnout Measure 2004-2006, were included. Registry data on sick leave spells from the response date until December 31, 2010 were obtained from the Swedish Social Insurance Agency. Logistic regression analysis was performed to assess odds ratios with 95% confidence intervals for the association between burnout and sick leave for the whole sample, while conditional logistic regression of the same-sex discordant twin pairs was used to estimate the association between burnout and sick leave, adjusting for familial confounding. The Bivariate Cholesky models were used to assess whether the covariation between burnout and sick leave was explained by common genetic and/or shared environmental factors. RESULTS: Burnout was a risk factor for sick leave due to stress-related and other mental disorders, and these associations were explained by familial factors. The phenotypic correlation between burnout and sick leave due to somatic conditions was 0.07 and the association was not influenced by familial factors. The phenotypic correlations between burnout and sick leave due to stress-related (0.26) and other mental disorders (0.30) were completely explained by common genetic factors. CONCLUSIONS: The association between burnout and sick leave due to stress-related and other mental disorders seems to be a reflection of a shared genetic liability.

Work-home interference and burnout: a study based on Swedish twins.

OBJECTIVE: This study sets out to investigate the impact of work-home interference on burnout in women and men, while taking genetic and family environmental factors into account. METHODS: A total of 4446 Swedish twins were included in the study. The effects of work-home conflict (WHC) and home-work conflict (HWC) on burnout between and within pairs were analyzed with co-twin control analyses. RESULTS: Both WHC and HWC were significantly associated with burnout. Genetic factors may be involved in the association between HWC and burnout in women. Familial factors were not involved for WHC and burnout, neither for women nor for men. CONCLUSIONS: This study shows the importance to encounter WHC per se to prevent burnout. Because of genetic confounding in HWC and burnout in women, preventive efforts may also take into account individual characteristics.

Dexamethasone stimulated gene expression in peripheral blood indicates glucocorticoid-receptor hypersensitivity in job-related exhaustion.

Work-related stress can lead to various health problems ranging from job-related exhaustion to psychiatric and somatic diseases. Biomarkers of job-related exhaustion could help to improve our understanding of the biological mechanisms and might be useful to guide prevention and treatment strategies. The present study included 12 male cases suffering from job-related exhaustion and 12 matched healthy controls. Severity of exhaustion was assessed with the Maslach Burnout Inventory (MBI) and the Shirom-Melamed Burnout Measure (SMBM). Whole genome expression profiles derived from whole blood cells (baseline and following glucocorticoid-receptor (GR) stimulation with 1.5mg dexamethasone p.o.) and corresponding plasma cortisol levels were analyzed. All cases participated in regular aerobic exercise for 12 consecutive weeks and were then re-assessed at follow-up for exhaustion symptoms as well as for cortisol levels and gene expression profiles. At baseline, we found increased basal cortisol levels and an enhanced suppression of plasma cortisol concentrations following dexamethasone in cases suffering from job-related exhaustion. Gene expression analysis revealed that 1.6-fold more transcripts were significantly regulated by dexamethasone in cases as compared to controls. At follow-up after 12 weeks of regular exercise training which was accompanied by significantly improved exhaustion severity scores, cortisol levels and gene expression profiles of cases normalized to the levels observed in controls. In conclusion, we detected GR-induced neuroendocrine and gene expression changes in cases suffering from job-related exhaustion which are in line with an increased sensitivity of GR function. This GR dysregulation normalized with symptom recovery.

The importance of genetic and shared environmental factors for the associations between job demands, control, support and burnout.

Within occupational health research, one of the most influential models is the Job Demands-Control-Support model. Numerous studies have applied the model to different domains, with both physical and psychological health outcomes, such as burnout. The twin design provides a unique and powerful research methodology for examining the effects of environmental risk factors on burnout while taking familial factors (genetic and shared environment) into account. The aim of the present study was to investigate the impact of familial factors on the associations of burnout with job demands, control and support. A total of 14,516 individuals from the Swedish Twin Registry, who were born between 1959 and 1986, and who participated in the Study of Twin Adults: Genes and Environment (STAGE) by responding to a web-based questionnaire in 2005, were included in the analyses. Of these, there were 5108 individuals in complete same-sex twin pairs. Co-twin control analyses were performed using linear mixed modeling, comparing between-pairs effects and within-pair effects, stratified also by zygosity and sex. The results indicate that familial factors are of importance in the association between support and burnout in both women and men, but not between job demands and burnout. There are also tendencies towards familial factors being involved in the association between control and burnout in men. These results offer increased understanding of the mechanisms involved in the associations between work stress and burnout.

Genome-wide scan of job-related exhaustion with three replication studies implicate a susceptibility variant at the UST gene locus.

Job-related exhaustion is the core dimension of burnout, a work-related stress syndrome that has several negative health consequences. In this study, we explored the molecular genetic background of job-related exhaustion. A genome-wide analysis of job-related exhaustion was performed in the GENMETS subcohort (n = 1256) of the Finnish population-based Health 2000 study. Replication analyses included an analysis of the strongest associations in the rest of the Health 2000 sample (n = 1660 workers) and in three independent populations (the FINRISK population cohort, n = 10 753; two occupational cohorts, total n = 1451). Job-related exhaustion was ascertained using a standard self-administered questionnaire (the Maslach Burnout Inventory (MBI)-GS exhaustion scale in the Health 2000 sample and the occupational cohorts) or a single question (FINRISK). A variant located in an intron of UST, uronyl-2-sulfotransferase (rs13219957), gave the strongest statistical evidence in the initial genome-wide study (P = 1.55 × 10(-7)), and was associated with job-related exhaustion in all the replication sets (P < 0.05; P = 6.75 × 10(-7) from the meta-analysis). Consistent with studies of mood disorders, individual common genetic variants did not have any strong effect on job-related exhaustion. However, the nominally significant signals from the allelic variant of UST in four separate samples suggest that this variant might be a weak risk factor for job-related exhaustion. Together with the previously reported associations of other dermatan/chondroitin sulfate genes with mood disorders, these results indicate a potential molecular pathway for stress-related traits and mark a candidate region for further studies of job-related and general exhaustion.

Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort.

BACKGROUND: Shift-working nurses are exposed to a stressful work environment, which puts them at an increased risk for burnout and depression. We explored the effect of environmental stress on serotonin transporter gene (SLC6A4) promoter methylation among nurses from high and low work stress environments. METHODOLOGY: Using bisulfite sequencing, we investigated the methylation status of five CpG residues of a CpG-rich region in the promoter of SLC6A4 by comparing female shift working nurses from a high work stress environment (n = 24) to low work stress environment (n = 25). We also analyzed the association of 5-HTTLPR polymorphism at 5' end of SLC6A4. Work stress was assessed by the Karasek's Model and possible signs of burnout or depression were measured by the Maslach Burnout Index General Survey and Beck Depression Index. Methylation levels were assessed by bisulfite sequencing of DNA extracted from peripheral blood leucocytes. Restriction enzyme treatment followed by standard PCR was used to identify 5-HTTLPR genotypes. PRINCIPAL FINDINGS: We found that nurses in the high stress environment had significantly lower promoter methylation levels at all five CpG residues compared to nurses in the low stress environment (p<0.01). There was no significant interaction of 5-HTTLPR genotype and work stress with methylation (p = 0.58). In unadjusted (bivariate) analysis, burnout was not significantly associated to methylation levels. However, when mutually adjusted for both, burnout and work stress were significant contributors (p = 0.038 and p<0.0001 respectively) to methylation levels. CONCLUSIONS: Our findings show that environmental stress is concurrent with decreased methylation of the SLC6A4 promoter. This may lead to increased transcriptional activity of the gene, increased reuptake of serotonin from synaptic clefts, and termination of the activity of serotonin. This could present a possible coping mechanism for environmental stress in humans that could eventually increase risk for disturbed functional capability and experience of depressed mood in long-term stress.

Genetic susceptibility to burnout in a Swedish twin cohort.

Most previous studies of burnout have focused on work environmental stressors, while familial factors so far mainly have been overlooked. The aim of the study was to estimate the relative importance of genetic influences on burnout (measured with Pines Burnout Measure) in a sample of monozygotic (MZ) and dizygotic (DZ) Swedish twins. The study sample consisted of 20,286 individuals, born 1959-1986 from the Swedish twin registry who participated in the cross-sectional study of twin adults: genes and environment. Probandwise concordance rates (the risk for one twin to be affected given that his/her twin partner is affected by burnout) and within pair correlations were calculated for MZ and DZ same--and opposite sexed twin pairs. Heritability coefficients i.e. the proportion of the total variance attributable to genetic factors were calculated using standard biometrical model fitting procedures. The results showed that genetic factors explained 33% of the individual differences in burnout symptoms in women and men. Environmental factors explained a substantial part of the variation as well and are thus important to address in rehabilitation and prevention efforts to combat burnout.

Val/Met polymorphism of the COMT gene moderates the association between job strain and early atherosclerosis in young men.

OBJECTIVE: Several studies support job strain as a risk factor for coronary heart disease (CHD) but null findings also exist. Individual differences in innate stress vulnerability might in part explain the mixed findings. COMT gene influences dopamine transmission and dopaminergic activity might moderate effects of stress on CHD risk. We examine whether COMT Val158Met polymorphism moderates the association between job strain and atherosclerosis. METHODS: Participants (mean age 32.5) were 347 women and 353 men from the population-based Young Finns study. Preclinical atherosclerosis was measured using carotid intima-media thickness (IMT) ultrasound. RESULTS: COMT polymorphism moderated the job strain-IMT association in men. Job strain was associated with higher IMT in Val/Val carriers but not among others. CONCLUSIONS: Our findings support a general model in which the interaction between genotype and job strain is assumed to predispose to increased atherosclerotic processes.