Bulk RNA sequencing for analysis of post COVID-19 condition in adolescents and young adults.

BACKGROUND: Post COVID-19 condition (PCC) is a complication of SARS-COV-2 infection and can lead to long-term disability. METHODS: The present study was designed to analyse the gene expression patterns of PCC through bulk RNA sequencing of whole blood and to explore the potential molecular mechanisms of PCC. Whole blood was collected from 80 participants enrolled in a prospective cohort study following SARS-CoV-2 infected and non-infected individuals for 6 months after recruitment and was used for bulk RNA sequencing. Identification of differentially expressed genes (DEG), pathway enrichment and immune cell deconvolution was performed to explore potential biological pathways involved in PCC. RESULTS: We have found 13 differentially expressed genes associated with PCC. Enriched pathways were related to interferon-signalling and anti-viral immune processes. CONCLUSION: The PCC transcriptome is characterized by a modest overexpression of interferon-stimulated genes, pointing to a subtle ongoing inflammatory response.

Expression of ANK3 moderates the association between childhood trauma and affective traits in severe mental disorders.

Exposure to early life trauma increases the risk of psychopathology later in life. Here we investigated if ANK3 mRNA levels influence the relationship between childhood trauma experiences and clinical characteristics in mental disorders. A sample of 174 patients with bipolar disorder and 291 patients with schizophrenia spectrum disorder were included. Patients were diagnosed using the Structured Clinical Interview for DSM-IV, and childhood trauma was assessed using the childhood trauma questionnaire. Age at illness onset and number of psychotic and affective episodes were assessed from interview and medical records. Current depressive symptoms were measured using the calgary depression scale for schizophrenia and the inventory for depressive symptomatology. ANK3 expression was analyzed in whole blood using the Illumina HumanHT-12 v4 Expression BeadChip. Analyses were carried out with the Process adjusted for confounders. Within the total sample, patients with both high ANK3 expression and with the most severe childhood sexual abuse had more manic/hypomanic episodes and an earlier age at onset of the first episode. ANK3 mRNA levels also moderated the relationship between emotional neglect and manic/hypomanic episodes. Our results suggest that ANK3 expression levels moderate the association between specific types of childhood trauma and affective traits in mental disorders.

Stress-induced headache in the general working population is moderated by the NRCAM rs2300043 genotype.

OBJECTIVES: Earlier findings suggest that social stress such as abusive supervision may promote pain. In the present study we examine the possible moderating role of genetic variability in the NRCAM gene in this process. METHODS: The data were collected through a national survey drawn from the National Central Employee Register by Statistics Norway. A total of 1,205 individuals returned both the questionnaire and the saliva kit. Abusive supervision was scored by a 5-item version of the Tepper's 2,000 scale. Headache was measured on a four-category scale; 'not bothered,' 'a little bothered,' 'considerably bothered', 'seriously bothered'. Genotyping with regards to NRCAM rs2300043 was carried out using Taqman assay. Ordinal logistic regression was used to analyse the data. RESULTS: For males exposed to abusive supervision, those carrying the rs2300043 CC genotype reported the highest levels of headache. Women showed a trend towards the opposite pattern. Women with the rs2300043 CC genotype seem to have a weaker effect of abusive supervision regarding reported headache than their male counterparts with the CC genotype when exposed to abusive supervision. CONCLUSIONS: The present results indicated that the association between abusive supervision and headache in men with the NRCAM rs2300043 C allele was stronger than in other men. This suggests that the NRCAM genotype in men is important for the tolerance of social stress e.g., repeated negative acts from a superior. In contrast, a trend, though non-significant, towards the opposite pattern was observed in women. Our result suggests that the NRCAM genotype in men manifestly affects stress-induced pain such as headache.

The impact of follower leadership position on transformational leadership as moderator of the association between work-related ambiguity and job satisfaction.

This two-part study examined if the buffering effect of transformational leadership on the association between work-related ambiguity and job satisfaction is contingent upon whether a follower holds a formal leadership position him/herself. Data from two separate surveys were employed: Study 1: A sample of 845 respondents from Belgium. Study 2: A national probability sample of 1,608 Norwegian employees. Study 1 showed that task ambiguity had a significant negative relation with job satisfaction, but that transformational leadership did only buffer the association between task ambiguity and job satisfaction among employees holding a formal position as a supervisor or manager. Study 2 extended Study 1 by adjusting for age and job tenure of subordinates as a confounding variable. Study 2 confirmed that transformational leadership had a significantly stronger impact on the observed association between role ambiguity and job satisfaction among respondents holding a supervisor or manager position. In conclusion, when considering job satisfaction as an outcome of work-related ambiguity, transformational leadership is mainly beneficial for followers holding a formal supervisor or manager position themselves. Our findings thereby question assumptions about the general effectiveness of transformational leadership.

Mapping of pituitary stress-induced gene regulation connects Nrcam to negative emotions.

Environmental stressors such as repeated social defeat may initiate powerful activation of subconscious parts of the brain. Here, we examine the consequences of such stress (induced by resident-intruder paradigm) on the pituitary gland. In male stressed vs. control rats, by RNA- and bisulfite DNA sequencing, we found regulation of genes involved in neuron morphogenesis and communication. Among these, Neuronal cell adhesion molecule (Nrcam) showed reduced transcription and reduced DNA methylation in a region corresponding to intron 1 in human NRCAM. Also, genetic variability in this area was associated with altered stress response in male humans exposed to repeated social defeat in the form of abusive supervision. Thus, our data show that the pituitary gene expression may be affected by social stress and that genetic variability in NRCAM intron 1 region influences stress-induced negative emotions. We hope our shared datasets will facilitate further exploration of the motions triggered by social stressors.

Patterns of pain complaints and insomnia symptoms are associated with abusive supervision in the Norwegian working population: a latent class analysis.

OBJECTIVES: Previous findings suggest that abusive supervision, i.e., subordinates' perceptions of their supervisor's behaviours as hostile (excluding physical aggression), may increase the risk of health complaints. In addition, recent data suggest that the FKBP5 genotype rs9470080 important in the regulation of cortisol release, influences the same outcome. Adding to this complexity, different health complaints often co-occur. The present study aimed to (1) uncover patterns of pain complaints and insomnia symptoms by using latent class analysis, (2) determine whether abusive supervision or FKBP5 rs9470080 was associated with these patterns, and (3) examine the interaction between abusive supervision and FKBP5 genotype regarding pain and insomnia symptoms. METHODS: The data was collected through a national probability survey of 5,000 employees drawn from the National Central Employee Register by Statistics Norway. Abusive supervision was measured by a 5-item version of the Tepper's 2000 scale. Pain and insomnia symptoms were measured by 5 items reflecting pain and 3 items reflecting insomnia. The FKBP5 rs9470080 genotyping was carried out using TaqMan assay. RESULTS: A total of 1,226 participants returned the questionnaire and the saliva kit sample. Based on these the latent class analyses revealed four classes based on response patterns of pain and insomnia symptoms. In the regression analysis, abusive supervision was a significant predictor for the response patterns. However, neither the FKBP5 nor the interaction between abusive supervision and FKBP5 showed significant contributions. CONCLUSIONS: In conclusion, awareness of the association between abusive supervision and the revealed four pain- and insomnia subgroups, and what separates them, may be important for prognosis and an optimal follow-up for those affected.

Spinal pain in employees exposed to abusive supervision: Evidence of a sex and CRHR1 CTC haplotype interaction.

Previous findings suggest that exposure to social stress in the form of abusive supervision may increase the risk of musculoskeletal disorders. In the present study, we examined the link between abusive supervision, the CRHR1 genotype and spinal pain. The data were collected through a national survey drawn from the National Central Employee Register by Statistics Norway. A total of 1226 individuals returned both the questionnaire and the saliva kit. Abusive supervision was measured by a 5-item version of the Tepper's 2000 scale. Spinal pain was measured by 3 items (neck-, upper and low back pain). Genotyping with regard to CRHR1 rs242941, rs242939 and rs1876828 was carried out using Taqman assay, and Phase v.2.1.1 was used to define the CRHR1 allele combinations. The analyses revealed that abusive supervision was associated with spinal pain. In particular, we observed a strong effect of abusive supervision on spinal pain in female +CTC/+CTC carriers (p = 0.002). Moreover, using +CTC/+CTC as a reference, +CTC/-CTC and -CTC/-CTC both showed protective effects (p = 0.024, p = 0.002, respectively). Also, our data demonstrated a clear sex and CRHR1 CTC haplotype interaction (p = 0.013). No such gene-environment interaction was seen in men. Our data demonstrated that the CRHR1 CTC haplotype may exacerbate the effect of abusive supervision on spinal pain in female employees. Hence, the present study supports the theory that both gender and the CRHR1 genotype, may moderate the pain responses to social stressors.

Workplace bullying increases the risk of anxiety through a stress-induced ß2-adrenergic receptor mechanism: a multisource study employing an animal model, cell culture experiments and human data.

OBJECTIVES: Several studies show that severe social stressors, e.g., in the form of exposure to workplace bullying in humans, is associated with negative mental health effects such as depression and anxiety among those targeted. However, the understanding of the underlying biological mechanisms that may explain the relationship between exposure to bullying and such negative health outcomes is scarce. The analyses presented here focus on understanding the role of the ß2-adrenergic receptors (ADRB2) on this association. METHODS: First, a resident-intruder paradigm was used to investigate changes in circulating norepinephrine (NE) in rat serum induced by repeated social defeat and its relationship with subsequent social behavior. Second, the direct effects of the stress-hormones NE and cortisol, i.e., synthetic dexamethasone (DEX), on the ADRB2 expression (qPCR) and monocyte chemoattractant protein-1 (MCP-1) release (immunoassay) was examined in cultured EL-1 cells. Third, in a probability sample of 1052 Norwegian employees, the 9-item short version of the Negative Acts Questionnaire-Revised (S-NAQ) inventory, Hopkins Symptom Checklist and genotyping (SNP TaqMan assay) were used to examine the association between social stress in the form of workplace bullying and anxiety moderated by the ADRB2 genotype (rs1042714) in humans. RESULTS: The present study showed a clear association between reduced social interaction and increased level of circulating NE in rats previously exposed to repeated social defeat. Parallel cell culture work, which was performed to examine the direct effects of NE and DEX on ADRB2, demonstrated ADRB2 downregulation and MCP-1 upregulation in cultured EL-1 cells. Genotyping with regard to the ADRB2 genotype; rs1042714 CC vs CG/GG, on human saliva samples, showed that individuals with CC reported more anxiety following exposure to bullying behaviors as compared to the G carriers. CONCLUSION: We conclude that workplace bullying promotes anxiety and threaten well-being through an ADRB2 associated mechanism.

Associations between exposure to workplace bullying and insomnia: a cross-lagged prospective study of causal directions.

OBJECTIVE: Workplace bullying has been established as a significant correlate of sleep problems. However, little is known regarding the causal direction between bullying and sleep. The aim of this study was to examine temporal relationships between bullying and symptoms of insomnia. METHODS: Reciprocal and prospective associations between exposure to workplace bullying and symptoms of insomnia were investigated in a national probability sample comprising 1149 Norwegian employees. Data stemmed from a two-wave full panel survey study with a 6-month time interval between the baseline and follow-up assessments. Models with stabilities, forward-, reverse-, and reciprocal associations were tested and compared using Structural Equation Modelling. Analyses were adjusted for age, gender, and the stability in the outcome variables over time. Workplace bullying was assessed with the nine-item Short Negative Acts Questionnaire. Insomnia was assessed with a previously validated three item scale reflecting problems with sleep onset, sleep maintenance, and early morning awakening. RESULTS: The forward association model, which showed that exposure to workplace bullying prospectively increased levels of insomnia (b = 0.08; p < 0.001), had best fit with the data [CFI = 0.94; TLI = 0.93; RMSEA = 0.049 (0.046-0.052)]. The reverse association model where insomnia influences risk of being subjected to bullying was not supported. CONCLUSION: Workplace bullying is a risk factor for later insomnia. There is a need for further studies on moderating and mediating variables that can explain how and when bullying influence sleep.

Low Back Pain With Persistent Radiculopathy; the Clinical Role of Genetic Variants in the Genes SOX5, CCDC26/GSDMC and DCC.

In a recently published genome-wide association study (GWAS) chronic back pain was associated with three loci; SOX5, CCDC26/GSDMC and DCC. This GWAS was based on a heterogeneous sample of back pain disorders, and it is unknown whether these loci are of clinical relevance for low back pain (LBP) with persistent radiculopathy. Thus, we examine if LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy is associated with the selected single nucleotide polymorphisms (SNPs); SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. In this prospective cohort study, subjects admitted to a secondary health care institution due to an acute episode of LBP with radiculopathy, reported back pain, leg pain, and Oswestry Disability Index (ODI), were genotyped and followed up at 12 months (n = 338). Kruskal-Wallis H test showed no association between the SNPs and back pain, leg pain or ODI. In conclusion, LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy, is not associated with the selected SNPs; SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. This absent or weak association suggests that the SNPs previously associated with chronic back pain are not useful as prognostic biomarkers for LBP with persistent radiculopathy.

The association between selected genetic variants and individual differences in experimental pain.

OBJECTIVES: The underlying mechanisms for individual differences in experimental pain are not fully understood, but genetic susceptibility is hypothesized to explain some of these differences. In the present study we focus on three genetic variants important for modulating experimental pain related to serotonin (SLC6A4 5-HTTLPR/rs25531 A>G), catecholamine (COMT rs4680 Val158Met) and opioid (OPRM1 rs1799971 A118G) signaling. We aimed to investigate associations between each of the selected genetic variants and individual differences in experimental pain. METHODS: In total 356 subjects (232 low back pain patients and 124 healthy volunteers) were genotyped and assessed with tests of heat pain threshold, pressure pain thresholds, heat pain tolerance, conditioned pain modulation (CPM), offset analgesia, temporal summation and secondary hyperalgesia. Low back pain patients and healthy volunteers did not differ in regards to experimental test results or allelic frequencies, and were therefore analyzed as one group. The associations were tested using analysis of variance and the Kruskal-Wallis test. RESULTS: No significant associations were observed between the genetic variants (SLC6A4 5-HTTLPR/rs25531 A>G, COMT rs4680 Val158Met and OPRM1 rs1799971 A118G) and individual differences in experimental pain (heat pain threshold, pressure pain threshold, heat pain tolerance, CPM, offset analgesia, temporal summation and secondary hyperalgesia). CONCLUSIONS: The selected pain-associated genetic variants were not associated with individual differences in experimental pain. Genetic variants well known for playing central roles in pain perception failed to explain individual differences in experimental pain in 356 subjects. The finding is an important contribution to the literature, which often consists of studies with lower sample size and one or few experimental pain assessments.

Leadership Style, Headache, and Neck Pain: The Moderating Role of the Catechol-O-Methyltransferase (COMT) Genotype.

OBJECTIVE: Leadership styles can influence subordinates' health. We investigated how the gene encoding the Catechol-O-Methyltransferase (COMT) enzyme (ie, COMT rs4680 Val158Met) influenced effects of abusive supervision and transformational leadership on subordinates' headache and neck pain. METHODS: Multiple group structural equation modeling (SEM) was employed to test associations of leadership with subordinates' pain 6 months after in a representative sample of the Norwegian working population (n = 996). Genotyping was performed by TaqMan technology. RESULTS: Abusive supervision was associated with increased risk, and transformational leadership with decreased risk, of headache and neck pain. Both leadership styles exhibited more pronounced effects in individuals with the Met/Met genotype. CONCLUSION: Met/Met employees were relatively vulnerable to adversity, but also relatively responsive to constructive leadership. Many workers may benefit more from constructive leadership than population-averaged associations might suggest.

The influence of age, gender and the FKBP5 genotype on subjective health complaints in the Norwegian working population.

OBJECTIVE: In the present study we examined the potential association between age, gender, the genetic variant FKBP5 rs9470080 and subjective health complaints. METHODS: The data were collected through a three-wave nationally representative survey of 1060 Norwegian employees drawn from the Norwegian Central Employee Register by Statistics Norway. The follow-up period was six months. Subjective health complaints were scored by eight items reflecting; headache, neck pain, mid- and low back pain, stomach cramps or intestinal discomfort, problems with sleep onset or maintenance and early morning awakening. Genotyping with regard to FKBP5 rs9470080, previously linked to cortisol sensitivity, was carried out using Taqman assay. RESULTS: The baseline data showed that in women, levels of subjective health complaints were highest among those above 50 years of age. Moreover, in women the rs9470080 CC variant at baseline was associated with higher levels of subjective health complaints. However, the effect size was not large, and no relationships were demonstrated between age or genotype and subjective health complaints in men. Also, the study variables were not related to any changes in the levels of subjective health complaints during the follow-up period. CONCLUSION: We conclude that our biology such as age and sex, but also single genetic variants found in non-sex chromosomes, may be important in understanding the mechanisms underlying subjective health complaints in the general working population.

Repeated social defeat promotes persistent inflammatory changes in splenic myeloid cells; decreased expression of ß-arrestin-2 (ARRB2) and increased expression of interleukin-6 (IL-6).

BACKGROUND: Previous studies suggest that persistent exposure to social stress in mammals may be associated with multiple physiological effects. Here, we examine the effects of social stress in rats, i.e. repeated social defeat, on behavior, hypothalamic-pituitary-adrenal (HPA)-axis and immune system. METHODS: A resident-intruder paradigm, where an intruder rat was exposed to social stress by a dominant resident rat for 1 hour each day for 7 consecutive days was used. The day after the last stress exposure in the paradigm the data were analyzed. Variation in social interaction was observed manually, whereas locomotion was analyzed off-line by a purpose-made software. Gene expression in the pituitary gland, adrenal gland and myeloid cells isolated from the spleen was measured by qPCR. RESULTS: The exposure to social stress induced decreased weight gain and increased locomotion. An increased nuclear receptor subfamily group C number 1 (NR3C1) expression in the pituitary gland was also shown. In myeloid cells harvested from the spleen, we observed decreased expression of the ß2-adrenergic receptor (ADRB2) and ß-arrestin-2 (ARRB2), but increased expression of interleukin-6 (IL-6). Subsequent analyses in the same cells showed that ARRB2 was negatively correlated with IL-6 following the stress exposure. CONCLUSION: Our results show that that the experience of social stress in the form of repeated social defeat in rats is a potent stressor that in myeloid cells in the spleen promotes persistent inflammatory changes. Future research is needed to examine whether similar inflammatory changes also can explain the impact of social stress, such as bullying and harassment, among humans.

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.Lay summaryUsing an animal model of social stress, we identified miR-146a, miR-30c and miR-223 as potentially important gene regulatory molecules that may be involved in the stress response. Interestingly, human genotypes affecting the expression of mature miR-30c and miR-223 had a moderating effect on the association between exposure to bullying and pain. Subjects with the miR-30c rs928508 GG genotype had a significantly stronger association between exposure to bullying behaviors and pain than other subjects. The same was observed in men with the miR-223 rs3848900 G genotype, as compared to other men.

Up-regulation of circulating microRNA-17 is associated with lumbar radicular pain following disc herniation.

BACKGROUND: Previous studies suggest that regulatory microRNAs (miRs) may modulate neuro-inflammatory processes. The purpose of the present study was to examine the role of miR-17 following intervertebral disc herniation. METHODS: In a cohort of 97 patients with leg pain and disc herniation verified on MRI, we investigated the association between circulating miR-17 and leg pain intensity. A rat model was used to examine possible changes in miR-17 expression in nucleus pulposus (NP) associated with leak of NP tissue out of the herniated disc. The functional role of miR-17 was addressed by transfection of miR-17 into THP-1 cells (human monocyte cell line). RESULTS: An association between the level of miR-17 in serum and the intensity of lumbar radicular pain was shown. Up-regulation of miR-17 in the rat NP tissue when applied onto spinal nerve roots and increased release of TNF following transfection of miR-17 into THP-1 cells were also observed. Hence, our data suggest that miR-17 may be involved in the pathophysiology underlying lumbar radicular pain after disc herniation. CONCLUSIONS: We conclude that miR-17 may be associated with the intensity of lumbar radicular pain after disc herniation, possibly through a TNF-driven pro-inflammatory mechanism.

Persistent lumbar radicular and low back pain; impact of genetic variability versus emotional distress.

OBJECTIVE: Earlier studies documenting the effect of candidate genes on recovery have seldom taken into consideration the impact of emotional distress. Thus, we aimed to assess the modifying effect of emotional distress on genetic variability as a predictor for pain recovery in lumbar radicular (LRP) and low back pain (LBP). RESULTS: The study population comprised 201 patients and mean age was 41.7 years. The significant association between MMP9 rs17576 (B = 0.71, 95% CI 0.18 to 1.24, p = 0.009) and pain recovery remained statistically significant after adjusting for pain intensity at baseline, age, gender, smoking, body mass index, pain localization and emotional distress (B = 0.68, 95% CI 0.18 to 1.18, p = 0.008). In contrast, the association between OPRM1 (B = - 0.85, 95% CI - 1.66 to - 0.05, p = 0.038) and pain recovery was abolished in the multivariate analysis (B = - 0.72, 95% CI - 1.46 to 0.02, p = 0.058). Hence, MMP9 rs17576 and emotional distress independently seem to predict persistent back pain. The predictive effect of OPRM1 rs179971 with regard to the same outcome is probably dependent on other factors including emotional processing. Trial registration The Regional Committee for Medical Research and Ethics reference number 2014/1754.

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.

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.

Cross-cultural Adaptation and Validation of the Norwegian Short-form McGill Pain Questionnaire-2 in Low Back-related Leg Pain.

STUDY DESIGN: A prospective observational study with translation and psychometric analyses of a questionnaire. OBJECTIVE: Cross-cultural adaptation of the Short-Form McGill Pain Questionnaire-2 into Norwegian. SUMMARY OF BACKGROUND DATA: The different versions of the McGill Pain Questionnaire (MPQ) have been important and influential tools for pain assessment. To more reliably assess qualities of both neuropathic and non-neuropathic pain, the Short-Form MPQ was revised in 2009 (SF-MPQ-2), including seven additional descriptors. No Norwegian adaptation of the SF-MPQ-2 has been performed. METHODS: A translation of the SF-MPQ-2 was performed based on established guidelines. Forward-translations were compared and discussed in an expert workgroup. A synthesis was achieved by consensus. A backward translation was reviewed and consolidated with the forward translations to confirm linguistic equivalence. A prefinal version was tested in eight patients, who were interviewed to evaluate acceptability and comprehension of the questionnaire. Minor changes were implemented. The questionnaire was externally proofread. The final Norwegian version (NSF-MPQ-2) was tested for content and construct validity and internal consistency reliability in a population with low back-related leg pain. RESULTS: The backward translation was in good accordance with the original version. The prefinal version showed excellent acceptability and comprehension in initial patient-testing. The NSF-MPQ-2 showed satisfactory content and construct validity, including responsiveness to change, and acceptable internal consistency reliability as measured by Cronbach's alpha. A confirmatory factor analysis showed poor fit for the established four-factor structure, especially regarding the neuropathic subscale. CONCLUSION: The NSF-MPQ-2 showed excellent acceptability and comprehension, satisfactory content and construct validity, including responsiveness to change, and internal consistency reliability as measured by Cronbach's alpha. However, a confirmatory factor analysis raised concerns regarding the factor-structure in the present population. Until more evidence emerges for the four-factor solution we suggest the NSF-MPQ-2 should be used as a single measure. LEVEL OF EVIDENCE: 3.