Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

BACKGROUND:Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. METHODOLOGY/PRINCIPAL FINDINGS:Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n=89) and controls (n=88) showing a small but significant increase of CRP levels in the patients. CONCLUSIONS/SIGNIFICANCE:MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured

Domains of Chronic Stress, Lifestyle Factors, and Allostatic Load in Middle-Aged Mexican-American Women

Abstract available at publisher's website

Predictors of mental health in female teachers

Objective: Teaching profession is characterised by an above-average rate of psychosomatic and mental health impairment due to work-related stress. The aim of the study was to identify predictors of mental health in female teachers. Material and Methods: A sample of 630 female teachers (average age 47±7 years) participated in a screening diagnostic inventory. Mental health was surveyed with the General Health Questionnaire GHQ-12. The following parameters were measured: specific work conditions (teacher-specific occupational history), scales of the Effort-Reward-Imbalance (ERI) Questionnaire as well as cardiovascular risk factors, physical complaints (BFB) and personal factors such as inability to recover (FABA), sense of coherence (SOC) and health behaviour. Results: First, mentally fit (MH+) and mentally impaired teachers (MH-) were differentiated based on the GHQ-12 sum score (MH+: < 5; MH-: ≥ 5); 18% of the teachers showed evidence of mental impairment. There were no differences concerning work-related and cardiovascular risk factors as well as health behaviour between MH+ and MH-. Binary logistic regressions identified 4 predictors that showed a significant effect on mental health. The effort-reward-ratio proved to be the most relevant predictor, while physical complaints as well as inability to recover and sense of coherence were identified as advanced predictors (explanation of variance: 23%). Conclusion: Contrary to the expectations, classic work-related factors can hardly contribute to the explanation of mental health. Additionally, cardiovascular risk factors and health behaviour have no relevant influence. However, effort-reward-ratio, physical complaints and personal factors are of considerable influence on mental health in teachers. These relevant predictors should become a part of preventive arrangements for the conservation of teachers' health in the future

Human mineralocorticoid receptor (MR) gene haplotypes modulate MR expression and transactivation: implication for the stress response

Stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in secretion of corticosteroids which facilitate behavioural adaptation. These effects exerted by corticosteroids are mediated by two brain corticosteroid receptor types, the mineralocorticoid receptor (MR), with a high affinity already occupied under basal conditions and the glucocorticoid receptor (GR), with a low affinity only activated during stress. Here, we studied MR gene haplotypes constituted by the two single nucleotide polymorphisms MR-2G/C (rs2070951) and MRI180V (rs5522). The haplotypes showed differences in cortisol-induced gene transcription and protein expression while the structural variant MRI180V did not affect ligand binding. Moreover, in a well characterized cohort of 166 school teachers these haplotypes have been associated with perceived chronic stress (Trier Inventory for the Assessment of Chronic Stress, TICS) and, in a subgroup of 47 subjects, with ACTH, cortisol and heart rate responses to acute psychosocial stress (Trier Social Stress Test, TSST). MR haplotypes were significantly associated with the TICS scales "excessive demands at work" and "social overload". Subjects homozygous for haplotype MR-2C/MRI180, which in vitro showed highest expression and transactivational activity, displayed the highest salivary cortisol (p<0.001), plasma cortisol (p=0.010), plasma ACTH (p=0.003) and heart rate (p=0.018) responses. It is concluded that the investigated MR haplotypes modulate cortisol-induced gene transcription in vitro. Moreover, these haplotypes may contribute to individual differences in perceived chronic stress as well as neuroendocrine and cardiovascular stress responses.Stress-related psychiatric disorders across the life spa

Association of a polymorphism in the H6PD gene and basal cortisol secretion, body fat mass and leptin level (Assoziation eines Polymorphismus im H6PD Gen mit basaler Cortisolsekretion, Fettmasse und Leptinwerten)

The hypothalamus-pituitary-adrenal (HPA) axix is vital for an organism's response to physical or psychosocial stimulation. Chronic dysregulation of HPA axis activity is related to several psychiatric and psychosomatic disorders. Cortisol, the end product of this endocrine system, affects a multitude of systems in the body, including the HPA axis itself and it also has an influence on behavior. The intracellular availability of cortisol is crucial for the regulation of this endocrine system. The enzyme hexose-6-phosphat-dehydrogenase (H6PDH) affects cortisol availability via its influenec on 11?-hydroxysteroid dehydrogenase type I (11?-HSDI)-activity, which regenerates cortisol from inactive cortisone. 116 healthy males (33 monozygotic &amp; 25 dizygotic twin pairs) were studied to estimate the association between a polymorphism in the exon 5 of the H6PD gene (R435Q, GA) and adrenocortical responses to psychosocial stress, basal salivary cortisol levels and body composition. Compared with subjects with the more frequent H6PD genotypers the homozygous AA-carriers displayed a significantly decreased cortisol awakening rise (CAR) as well as lower daytime cortisol levels. In response to stress, the AA-carriers exhibited a trend towards lower cortisol and ACH responses compared with GG- and GA-carriers. In addition, significantly higher levels of leptin and amount of body fat were observed in AA-carriers. We hypothesize that the R453Q polymorphism in the H6PD gene might influence intracellular cortisol availability and thus affect HPA axis regulation.<br/

Laparoscopic liver resection in Caroli disease: a single-centre case series

Background: Liver resection is the treatment of choice for patients with localised Caroli disease. While liver resection was traditionally performed as open procedure, this case series aims to evaluate the safety and efficacy of minimally invasive, laparoscopic liver surgery in these patients. Methods: A systematic review of electronic case files of patients seen between April 2015 and December 2017 at the Department of Surgery, Charité University Hospital Berlin, was conducted. Patients with Caroli disease in whom laparoscopic liver resection had been performed were identified and analysed in this single-centre case series. Results: Seven patients who underwent laparoscopic liver surgery for Caroli syndrome were identified and presented with a median age of 49 (range = 44–66) years, of which four (57%) were female. Preoperatively, six patients were classified as the American Society of Anaesthesiologists (ASA) 2 and one patient as ASA 3. Two operations were performed as single-incision laparoscopic surgery, whereas the others were done as multi-incision laparoscopic surgery. One patient required a conversion to an open procedure. The length of operation varied between patients, ranging from 128 to 758 min (median = 355). The length of stay in the intensive care unit ranged from 0 to 2 days. Two patients presented with post-operative complications (Clavien–Dindo Grade ≥3a), whereas no patient died. In histopathological analysis, all patients demonstrated characteristic findings of Caroli disease and no cholangiocarcinoma was found. Conclusion: These results indicate that minimally invasive, laparoscopic liver surgery is a safe and efficacious treatment option for patients with Caroli disease who require liver resection