Interaction of childhood trauma with BDNF and FKBP5 gene polymorphisms in predicting burnout in general occupational groups.

Both the BDNF gene rs6265 and the FKBP5 gene rs1360780 polymorphisms are independently associated with adult psychotic-like experiences, when exposed to high childhood abuse; however, it remains unclear whether the relationship between childhood abuse and burnout is moderated by these two single nucleotide polymorphisms (SNPs). Furthermore, there is an interaction between glucocorticoid receptor transcriptional activity and BDNF signaling. Therefore, we investigated the interaction of these two SNPs with childhood trauma in predicting burnout. We recruited 990 participants (mean age 33.06 years, S.D. = 6.31) from general occupational groups and genotyped them for rs6265 and rs1360780. Burnout, childhood trauma, resilience, and job stress were measured through a series of rating scales. Gene-by-environment and gene-by-gene-by-environment interactions were examined using linear hierarchical regression and PROCESS macro in SPSS. Covariates included demographics and resilience. We found that rs6265 moderated the association between job stress and emotional exhaustion. Both rs6265 and rs1360780 moderated the association between childhood abuse and cynicism. There was significant interaction of childhood abuse × rs6265 × rs1360780 on emotional exhaustion and reduced personal accomplishment, so that rs6265 CC genotype and rs1360780 TT genotype together predicted higher levels of emotional exhaustion under high childhood abuse, while rs6265 TT genotype and rs1360780 CC genotype together exerted a resilient effect on reduced personal accomplishment in the face of childhood abuse. Our findings suggest that the rs6265 CC genotype and rs1360780 TT genotype may jointly contribute to increased risk of burnout under childhood trauma.

Genotype-genotype interactions of the OXTR gene polymorphisms are associated with self-reported daytime dysfunction, sleep latency and personal distress.

The oxytocin receptors located in the corticotropin-releasing factor neurons of the paraventricular nucleus are stimulated by oxytocin. Oxytocin functions as the regulator of the corticotropin-releasing factor system and in turn promotes sleep quality. The objective of this study was to examine the main and genotype-genotype interactive effects of the oxytocin receptor gene (OXTR) polymorphisms on sleep quality. A total of 324 participants were randomly recruited from a university in Beijing, China. Sleep quality was measured with the Pittsburgh Sleep Quality Index. The OXTR single-nucleotide polymorphisms (rs2254298, rs2268498, rs13316193, rs2268490 and rs2268491) were genotyped. The results showed that gender and age were associated with various empathy traits (all p < 0.001). The Pittsburgh Sleep Quality Index was positively correlated with the Personal Distress subscale of empathy (p < 0.001). Both rs2254298 and rs2268491 interacted with rs13316193 to influence daytime dysfunction and Personal Distress (all p < 0.05), indicating that in individuals with rs13316193 CC/CT genotype, those with rs2254298 AA/AG or rs2268491 TT/TC genotypes displayed higher daytime dysfunction and Personal Distress scores than those with rs2254298 GG or rs2268491 CC genotypes. Conversely, among the individuals with rs2254298 GG or rs2268491 CC genotypes, the rs13316193 C allele carriers had lower daytime dysfunction and Personal Distress scores than rs13316193 TT homozygotes. There was also a significant interaction between rs2268490 and rs2268498 on the sleep latency dimension of the Pittsburgh Sleep Quality Index. Our findings reveal for the first time the genotype-genotype interactions of the OXTR gene on sleep quality, which may open new research avenues for studying psychopathology involving sleep problems.

Genetic polymorphisms in the 5-HT and endocannabinoid systems moderate the association between childhood trauma and burnout in the general occupational population.

BACKGROUND: Interactions between the serotonin (5-HT) and endocannabinoid (eCB) systems have been reported in the psychopathology of stress-related symptoms, while their interplay in regulating the relationship between childhood trauma and burnout remains unclear. In this study, we investigated the interaction of childhood trauma with genetic polymorphisms in these two systems in predicting burnout. METHODS: Burnout, childhood trauma, and job stress were assessed using rating scales in 992 general occupational individuals. Genetic polymorphisms including HTR2A rs6313, 5-HTT rs6354 and FAAH rs324420, were genotyped. Linear hierarchical regression analysis and PROCESS macro in SPSS were used to examine two- and three-way interactions. RESULTS: There were significant interactions of job stress × HTR2A rs6313 and childhood abuse × FAAH rs324420 on reduced personal accomplishment. Moreover, we found significant three-way interactions of childhood abuse × FAAH rs324420 × HTR2A rs6313 on cynicism and reduced personal accomplishment, childhood abuse × FAAH rs324420 × 5-HTT rs6354 on emotional exhaustion, and childhood neglect × FAAH rs324420 × 5-HTT rs6354 on reduced personal accomplishment. These results suggest that the FAAH rs324420 A allele carriers, when with some specific genetic polymorphisms of 5-HT system, would show more positive associations between childhood trauma and burnout. CONCLUSIONS: Genetic polymorphisms in the 5-HT and eCB systems may jointly moderate the impact of childhood trauma on burnout.

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.

Interaction between the BDNF rs11030101 genotype and job stress on cognitive empathy.

BACKGROUND: Empathy refers to an individual's ability to experience the emotional and cognitive processes of another person during social interactions. Although many studies have examined the effects of genetic variation on emotional empathy, little is currently known about whether genetic factors may influence cognitive empathy. This study investigated the relationship between BDNF rs11030101 genotype, job stress, and empathy, especially cognitive empathy, in a Chinese Han population. METHODS: A cross-sectional design was used and 340 participants were recruited from a university in Beijing. Interpersonal Reactivity Index (IRI) was used to measure empathy. Job stress was measured using House and Rizzo's Job Stress Scale. The BDNF rs11030101 was genotyped in all participants. RESULTS: Gender and age were associated with various IRI subscales (p < 0.001). After controlling for gender, age and education level, BDNF rs11030101 genotype had no main effect on all empathy subscales (p > 0.05). Job stress was negatively associated with Perspective Taking (p = 0.006) and positively associated with Personal Distress (p < 0.001). In addition, the BDNF rs11030101 genotype modulated the relationship between job stress and Fantasy (p = 0.013), indicating that T allele carriers had higher Fantasy scores at higher job stress and lower Fantasy scores at lower job stress than AA homozygotes. This interaction was only present in women. LIMITATIONS: The sample size and single-nucleotide polymorphism are limited, and the cross-sectional design should be improved. CONCLUSIONS: Female university faculty with the BDNF rs11030101 T allele may utilize higher emotional job demands, thereby fostering their cognitive empathy.

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.

Interaction between job stress and the BDNF Val66Met polymorphism affects depressive symptoms in Chinese healthcare workers.

BACKGROUND: Chronic exposure to job-related stress can lead to depression and BDNF polymorphism may play an important role in this process. The role of the stress × BDNF Val66Met interaction in depression has been studied widely using childhood stress, but few studies have utilized chronic stress in adulthood as a moderator. This study was to examine the chronic stress × BDNF Val66Met interaction in job-related depression in the healthcare workers in a Chinese Han population, which has not been reported yet. METHODS: Using a cross-sectional design, 243 doctors and nurses were recruited from a general hospital in Beijing, and were assessed for depression with Self-rating Depression Scale (SDS), and the stress using the House and Rizzo's Work Stress Scale. The BDNF Val66Met polymorphism was genotyped. RESULTS: There was a significant positive association between job stress and depressive scores (p < 0.001). No significant main effect of the BDNF Val66Met genotype on depressive symptoms was observed (p > 0.05). A statistically significant interaction between BDNF Val66Met and job stress on depressive symptoms was found (p < 0.05); individuals with Val/Val genotype showed a higher SDS score than Met allele carriers only in the low-stress group, without significant differences in SDS score between the BDNF Val66Met subgroups in medium- or high-stress group. LIMITATIONS: Limitations include cross-sectional study design, the small sample size only in healthcare workers and only one polymorphism in BDNF gene was analyzed. CONCLUSIONS: Our results suggest a close relationship between job-related stress and depression, and the interaction of the BDNF Val66Met polymorphism and chronic stress in adulthood may impact the depressive symptoms.

Serum ApoB levels in depressive patients: associated with cognitive deficits.

Cognitive deficits have been regarded as one of the most significant clinical symptoms of depressive disorder. Accumulating evidence has shown that apolipoprotein B (ApoB) levels, which are responsible for inducing neurodegeneration, may be involved in cognitive deficits. This study examines cognitive deficits, and the correlation of serum ApoB levels with cognitive deficits of depressive disorder. 90 depressive patients and 90 healthy controls with matched age and gender were recruited. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Serum ApoB levels in depressive patients were measured by immunoturbidimetric method. Our results showed that depressive patients had lower scores of cognition including RBANS total score and subscales of language and delayed memory (all, p < 0.001) than healthy controls after controlling for the variables. The differences in cognitive functions also passed Bonferroni corrections. Serum ApoB levels were negatively correlated with delayed memory score in depressive patients (r = -0.30, p = 0.01). Furthermore, stepwise multivariate regression analysis indicated that serum ApoB levels independently contributed to delayed memory in depressive patients (t = -2.68, p = 0.01). Our findings support that serum ApoB levels may be involved in delayed memory decline in depressive patients. Depressive patients also experience greater cognitive deficits, especially in delayed memory and language than healthy controls.

[Study on oxidative function injury of Al exposure on primary cultured neuron mitochondria].

OBJECTIVE: To study the possible mechanism of Al neurotoxicity, we evaluated the oxidative function injury of mitochondria in the primary cultured neurons that were exposed to various concentrations of AlCl3. METHODS: Neurons from newborn SD rats were primarily cultured. Then they were exposed to AlCl3 of 0 micromol/L, 50 micromol/L, 100 micromol/L, and 500 micromol/L. The neuron death rate, mitochondria enzyme activity, mitochondria reactive oxygen species (ROS) and mitochondria membrane potential (MMP) were tested then. RESULTS: When the concentration of AlCl3 increased (0 micromol/L, 50 micromol/L, 100 micromol/L, 500 micromol/L), the death rate increased (10.53%, 11.99%, 12.03%, 25.00%), mitochondria enzyme activity decreased (0.56, 0.47, 0.42, 0.32), ROS increased (17.12, 19.71, 29.67, 45.46) and MMP decreased(8.03, 8.02, 4.69, 3.01). CONCLUSION: Al exposure could cause mitochondria oxidative function injury in the primarily cultured rats, which may be the one of the possible mechanism of Al toxicity.

The novel oxidative stress marker thioredoxin is increased in first-episode schizophrenic patients.

Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in various stages of schizophrenia. Serum TRX levels were determined using ELISA from 60 never-medicated first-episode and 66 medicated chronic schizophrenia patients and 66 healthy control subjects matched for age and gender. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed that group comparison between first-episode and chronic patients and control groups revealed significantly increased serum TRX only in first-episode patients. Increased levels of TRX in patients experiencing an acute stage schizophrenic episode was also significantly higher compared to chronic schizophrenic patients on antipsychotic medication. Serum TRX was also positively correlated with positive symptoms of schizophrenia. Our results suggest oxidative stress occurs in an acute stage of schizophrenic episode and may have an important role in pathogenesis and symptomology of schizophrenia. Lower TRX levels in chronic patients treated with antipsychotics may have implications for treatment outcome.