The 5-HTTLPR rs25531 LALA-genotype increases the risk of insomnia symptoms among shift workers

Background Previous studies indicate that shift work tolerance may be associated with individual factors including genetic variability in the gene encoding the serotonin transporter 5-HTT (SLC6A4). The present study aimed to explore the interaction between work schedule (shift work versus non-shift work), genetic variability in SLC6A4 and insomnia symptoms. Methods The study was based on a national probability sample survey of 987 Norwegian employees drawn from The Norwegian Central Employee Register by Statistics Norway. Insomnia symptoms were assessed by three items reflecting problems with sleep onset, sleep maintenance, and early morning awakenings. Genotyping concerning SLC6A4 (the 5-HTTLPR S versus L and the SNP rs25531 A versus G) was carried out using a combination of gel-electrophoresis and TaqMan assay. Results Using the LALA genotype as a reference a main effect of the SS genotype (B = 0.179; 95% CI = 0.027–0.330) was found. In addition, a main effect of work schedule (0 = non shift, 1 = shift work) was found (B = 0.504; 95% CI = 0.185–0.823). The genotype x work schedule interaction was significant for all genotypes; SLA (B = −0.590; 95% CI = −0.954–0.216), LALG (B = −0.879; 95% CI = −1.342–0.415), SLG (B = −0.705; 95% CI = −1.293–0.117) and SS (B = −0.773; 95% CI = −1.177–0.369) indicating higher insomnia symptom scores among LALA-participants compared to participants with other genotypes when working shifts. Conclusions The ability to cope with shift work is associated with the combination of the SLC6A4 variants 5-HTTLPR and SNP rs25531. Our findings demonstrated that the LALA-genotype increases the risk of insomnia symptoms among shift workers.acceptedVersio

Exposure to workplace bullying, distress, and insomnia. The moderating role of the miR-146a genotype

Several lines of evidence show that systematic exposure to negative social acts at the workplace i.e., workplace bullying, results in symptoms of depression and anxiety among those targeted. However, little is known about the association between bullying, inflammatory genes and sleep problems. In the present study, we examined the indirect association between exposure to negative social acts and sleep through distress, as moderated by the miR-146a genotype. The study was based on a nationally representative survey of 1179 Norwegian employees drawn from the Norwegian Central Employee Register by Statistics Norway. Exposure to workplace bullying was measured with the 9-item version of Negative Acts Questionnaire – Revised (NAQ-R) inventory. Seventeen items from Hopkins Symptom Checklist (HSCL-25) was used to measure distress. Insomnia was assessed with three items reflecting problems with sleep onset, maintenance of sleep and early morning awakening. Genotyping with regard to miR146a rs2910164, previously linked to inflammatory processes, was carried out using Taqman assay. The data revealed that individuals systematically exposed to negative social acts at the workplace reported higher levels of sleep problems than non-exposed individuals. Moreover, the relationship between distress induced by exposure to negative social acts and insomnia was significantly stronger for individuals with the miR-146a GG genotype. Thus, the miR-146a genotype moderated the association between distress and insomnia among individuals exposed to negative social acts. The present report support the hypothesis that inflammation could play a role in stress-induced insomnia among individuals exposed to workplace bullying.publishedVersio

Exposure to workplace bullying, microRNAs and pain. Evidence of a moderating effect of miR-30c rs928508 and miR-223 rs3848900

Prolonged exposure to bullying behaviors may give rise to symptoms such as anxiety, depression and chronic pain. Earlier data suggest that these symptoms often are associated with stress-induced low-grade systemic inflammation. Here, using data from both animals and humans, we examined the moderating role of microRNAs (miRNAs, miRs) in this process. In the present study, a resident-intruder paradigm, blood samples, tissue harvesting and subsequent qPCR analyses were used to screen for stress-induced changes in circulating miRNAs in rats. The negative acts questionnaire (NAQ), TaqMan assays and a numeric rating scale (NRS) for pain intensity were then used to examine the associations among bullying behaviors, relevant miRNA polymorphisms and pain in a probability sample of 996 Norwegian employees. In rats, inhibited weight gain, reduced pituitary POMC expression, adrenal Nr3c1 mRNA downregulation, as well as increased miR-146a, miR-30c and miR-223 in plasma were observed following 1 week of repeated exposure to social stress. When following up the miRNA findings from the animal study in the human working population, a stronger relationship between NAQ and NRS scores was observed in subjects with the miR-30c GG genotype (rs928508) compared to other subjects. A stronger relationship between NAQ and NRS scores was also seen in men with the miR-223 G genotype (rs3848900) as compared to other men. Our findings show that social stress may induce many physiological changes including changed expression of miRNAs. We conclude that the miR-30c GG genotype in men and women, and the miR-223 G genotype in men, amplify the association between exposure to bullying behaviors and pain.publishedVersio

Serum amyloid A1 and pregnancy zone protein in pregnancy complications and correlation with markers of placental dysfunction

BACKGROUND: Hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, and chronic hypertension), diabetes mellitus, and placental dysfunction confer an increased risk of long-term maternal cardiovascular disease. Preeclampsia is also associated with acute atherosis that involves lesions of uteroplacental spiral arteries, resembling early stages of atherosclerosis. Serum amyloid A1 is involved in hypercoagulability and atherosclerosis and may aggregate into amyloid—aggregations of misfolded proteins. Pregnancy zone protein may inhibit amyloid aggregation. Amyloid is involved in Alzheimer's disease and cardiovascular disease; it has been identified in preeclampsia, but its role in preeclampsia pathophysiology is unclear. OBJECTIVE: We hypothesized that serum amyloid A1 would be increased and pregnancy zone protein decreased in hypertensive disorders of pregnancy and diabetic pregnancies and that serum amyloid A1 and pregnancy zone protein would correlate with placental dysfunction markers (fetal growth restriction and dysregulated angiogenic biomarkers) and acute atherosis. STUDY DESIGN: Serum amyloid A1 is measurable in both the serum and plasma. In our study, plasma from 549 pregnancies (normotensive, euglycemic controls: 258; early-onset preeclampsia: 71; late-onset preeclampsia: 98; gestational hypertension: 30; chronic hypertension: 9; diabetes mellitus: 83) was assayed for serum amyloid A1 and pregnancy zone protein. The serum levels of angiogenic biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor were available for 547 pregnancies, and the results of acute atherosis evaluation were available for 313 pregnancies. The clinical characteristics and circulating biomarkers were compared between the pregnancy groups using the MannWhitney U, chi-squared, or Fisher exact test as appropriate. Spearman’s rho was calculated for assessing correlations. RESULTS: In early-onset preeclampsia, serum amyloid A1 was increased compared with controls (17.1 vs 5.1 mg/mL, P<.001), whereas pregnancy zone protein was decreased (590 vs 892 mg/mL, P=.002). Pregnancy zone protein was also decreased in diabetes compared with controls (683 vs 892 mg/mL, P=.01). Serum amyloid A1 was associated with placental dysfunction (fetal growth restriction, elevated soluble fmslike tyrosine kinase-1 to placental growth factor ratio). Pregnancy zone protein correlated negatively with soluble fms-like tyrosine kinase-1 to placental growth factor ratio in all study groups. Acute atherosis was not associated with serum amyloid A1 or pregnancy zone protein. CONCLUSION: Proteins involved in atherosclerosis, hypercoagulability, and protein misfolding are dysregulated in early-onset preeclampsia and placental dysfunction, which links them and potentially contributes to future maternal cardiovascular disease

Exposure to Workplace Bullying, Distress, and Insomnia: The Moderating Role of the miR-146a Genotype

Several lines of evidence show that systematic exposure to negative social acts at the workplace i.e., workplace bullying, results in symptoms of depression and anxiety among those targeted. However, little is known about the association between bullying, inflammatory genes and sleep problems. In the present study, we examined the indirect association between exposure to negative social acts and sleep through distress, as moderated by the miR-146a genotype. The study was based on a nationally representative survey of 1179 Norwegian employees drawn from the Norwegian Central Employee Register by Statistics Norway. Exposure to workplace bullying was measured with the 9-item version of Negative Acts Questionnaire – Revised (NAQ-R) inventory. Seventeen items from Hopkins Symptom Checklist (HSCL-25) was used to measure distress. Insomnia was assessed with three items reflecting problems with sleep onset, maintenance of sleep and early morning awakening. Genotyping with regard to miR-146a rs2910164, previously linked to inflammatory processes, was carried out using Taqman assay. The data revealed that individuals systematically exposed to negative social acts at the workplace reported higher levels of sleep problems than non-exposed individuals. Moreover, the relationship between distress induced by exposure to negative social acts and insomnia was significantly stronger for individuals with the miR-146a GG genotype. Thus, the miR-146a genotype moderated the association between distress and insomnia among individuals exposed to negative social acts. The present report support the hypothesis that inflammation could play a role in stress-induced insomnia among individuals exposed to workplace bullying

Intervertebral disc herniation, spinal nociceptive signaling and proinflammatory mediators

Lumbar disc herniation may affect the spinal nerve roots through mechanical pressure, but may also induce a local inflammatory response. Therefore, in an animal model mimicking the clinical situation after intervertebral disc herniation, the spinal nociceptive signaling and the gene expression changes in nucleus pulposus (NP) and dorsal root ganglion (DRG) tissue were studied. In addition, the effect of minocycline on the spinal nociceptive signaling and on the changes in gene expression in NP tissue was investigated. Electrophysiological recordings showed that NP applied onto the dorsal nerve roots of female Lewis rats induced a significant increase in spinal nociceptive signaling. Minocycline, when applied together with NP, attenuated this increase, without having any persistent effect on nociceptive activity by itself. Furthermore, qPCR analysis of the NP tissue exposed to the dorsal nerve roots showed an increase in the gene expression of IL-1ß, Csf1 and CD68. The upregulation of IL-1ß and Csf1 suggests that NP has a pro-inflammatory effect, underlying the pro-nociceptive process after disc herniation. In addition, the upregulation of CD68 indicates phagocytic activation of NP cells following contact with the nerve roots. We also demonstrated an upregulation of FKN and its receptor CX3CR1 in NP tissue. This upregulation indicates a new mechanism for NP in the induction and/or maintenance of pain hypersensitivity. In the DRG, after NP was exposed to the dorsal nerve roots, the gene expression of TNFα, FKN and CX3CR1 was also upregulated. It is likely that this upregulation affects the excitability of primary afferent nerve fibers. This could be related to the positive feedback loop involving satellite glial cells and neurons. Minocycline inhibited the increase in gene expression of IL-1ß, Csf1, CD68, FKN and CX3CR1 in NP tissue, demonstrating an inhibitory effect on these cells, possibly through MAPK p38 inhibition. The present study suggests that disc herniation increases the excitability in nociceptive pathways, possibly through a mechanism involving both NP cells and satellite glial cells

Hyperexcitability in Spinal WDR Neurons following Experimental Disc Herniation Is Associated with Upregulation of Fractalkine and Its Receptor in Nucleus Pulposus and the Dorsal Root Ganglion

Introduction. Lumbar radicular pain following intervertebral disc herniation may be associated with a local inflammatory response induced by nucleus pulposus (NP) cells. Methods. In anaesthetized Lewis rats, extracellular single unit recordings of wide dynamic range (WDR) neurons in the dorsal horn and qPCR were used to explore the effect of NP application onto the dorsal nerve roots (L3–L5). Results. A clear increase in C-fiber response was observed following NP conditioning. In the NP tissue, the expression of interleukin-1β (IL-1β), colony stimulating factor 1 (Csf1), fractalkine (CX3CL1), and the fractalkine receptor CX3CR1 was increased. Minocycline, an inhibitor of microglial activation, inhibited the increase in neuronal activity and attenuated the increase in IL-1β, Csf1, CX3L1, and CX3CR1 expression in NP tissue. In addition, the results demonstrated an increase in the expression of TNF, CX3CL1, and CX3CR1 in the dorsal root ganglions (DRGs). Conclusion. Hyperexcitability in the pain pathways and the local inflammation after disc herniation may involve upregulation of CX3CL1 signaling in both the NP and the DRG

The 5-HTTLPR rs25531 LALA-genotype increases the risk of insomnia symptoms among shift workers

Background Previous studies indicate that shift work tolerance may be associated with individual factors including genetic variability in the gene encoding the serotonin transporter 5-HTT (SLC6A4). The present study aimed to explore the interaction between work schedule (shift work versus non-shift work), genetic variability in SLC6A4 and insomnia symptoms. Methods The study was based on a national probability sample survey of 987 Norwegian employees drawn from The Norwegian Central Employee Register by Statistics Norway. Insomnia symptoms were assessed by three items reflecting problems with sleep onset, sleep maintenance, and early morning awakenings. Genotyping concerning SLC6A4 (the 5-HTTLPR S versus L and the SNP rs25531 A versus G) was carried out using a combination of gel-electrophoresis and TaqMan assay. Results Using the LALA genotype as a reference a main effect of the SS genotype (B = 0.179; 95% CI = 0.027–0.330) was found. In addition, a main effect of work schedule (0 = non shift, 1 = shift work) was found (B = 0.504; 95% CI = 0.185–0.823). The genotype x work schedule interaction was significant for all genotypes; SLA (B = −0.590; 95% CI = −0.954–0.216), LALG (B = −0.879; 95% CI = −1.342–0.415), SLG (B = −0.705; 95% CI = −1.293–0.117) and SS (B = −0.773; 95% CI = −1.177–0.369) indicating higher insomnia symptom scores among LALA-participants compared to participants with other genotypes when working shifts. Conclusions The ability to cope with shift work is associated with the combination of the SLC6A4 variants 5-HTTLPR and SNP rs25531. Our findings demonstrated that the LALA-genotype increases the risk of insomnia symptoms among shift workers

The 5-HTTLPR rs25531 LALA-genotype increases the risk of insomnia symptoms among shift workers

Background Previous studies indicate that shift work tolerance may be associated with individual factors including genetic variability in the gene encoding the serotonin transporter 5-HTT (SLC6A4). The present study aimed to explore the interaction between work schedule (shift work versus non-shift work), genetic variability in SLC6A4 and insomnia symptoms. Methods The study was based on a national probability sample survey of 987 Norwegian employees drawn from The Norwegian Central Employee Register by Statistics Norway. Insomnia symptoms were assessed by three items reflecting problems with sleep onset, sleep maintenance, and early morning awakenings. Genotyping concerning SLC6A4 (the 5-HTTLPR S versus L and the SNP rs25531 A versus G) was carried out using a combination of gel-electrophoresis and TaqMan assay. Results Using the LALA genotype as a reference a main effect of the SS genotype (B = 0.179; 95% CI = 0.027–0.330) was found. In addition, a main effect of work schedule (0 = non shift, 1 = shift work) was found (B = 0.504; 95% CI = 0.185–0.823). The genotype x work schedule interaction was significant for all genotypes; SLA (B = −0.590; 95% CI = −0.954–0.216), LALG (B = −0.879; 95% CI = −1.342–0.415), SLG (B = −0.705; 95% CI = −1.293–0.117) and SS (B = −0.773; 95% CI = −1.177–0.369) indicating higher insomnia symptom scores among LALA-participants compared to participants with other genotypes when working shifts. Conclusions The ability to cope with shift work is associated with the combination of the SLC6A4 variants 5-HTTLPR and SNP rs25531. Our findings demonstrated that the LALA-genotype increases the risk of insomnia symptoms among shift workers