Workplace bullying increases the risk of anxiety through a stress-induced β2-adrenergic receptor mechanism: a multisource study employing an animal model, cell culture experiments and human data

Abstract

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 β2-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.

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

“…The difference between the data of mice and rats could be related to minor differences in the handling of the animals and the resident-intruder protocol, and a suggestion for standardized protocol has recently been published (Munshi et al, 2022). Anyhow, when we previously examined the SPD rats 24 h after the last stress exposure to discover persistent effects on social behavior or weight gain, we did not observe any ''resilient'' group based on social avoidance among the stress-exposed rats (Jacobsen et al, 2020;Rajalingam et al, 2021), as might be expected if we had carried out the experiment in inbreed mice (Nasca et al, 2019).…”

“…We have recently demonstrated that repeated social defeat (the resident-intruder paradigm) is a strong stressor that may induce behavioral changes associated with reduced weight gain and increased impulsivity or locomotion 24 h after the last experience of social defeat in rats (Jacobsen et al, 2020;Rajalingam et al, 2020). A correlation between reduced social behavior and increased plasma (nor)epinephrine in animals exposed to social stress has also been observed (Rajalingam et al, 2021). Thus, it seems plausible that such social stressors, i.e., the asymmetry of power (Rajalingam et al, 2020), may trigger long-term changes in the hypothalamus-pituitary-adrenal (HPA) axis and subsequent stress-related biological processes underlying fear and nervousness (Smith and Vale, 2006).…”

“…Previous findings suggest that environmental stressors, such as repeated social defeat (Jacobsen et al, 2020;Rajalingam et al, 2020), may be associated with fear and behavioral alterations (McKim et al, 2018;Wohleb et al, 2014). For example, repeated social defeat in social mammals triggers activation of subconscious parts of the brain, which in turn promotes nervousness (Rajalingam et al, 2021;Wohleb et al, 2014). In rats, exposure to social stress may be seen as momentary submissive supine posture, freeze or flight, and later vulnerability toward cued fear memory dysfunction (Mancini et al, 2021).…”

Association of Workplace Bullying with Suicide Ideation and Attempt Among Chinese Nurses During the COVID-19 Pandemic

“…When this psychological pain reaches the threshold of an individual, it can lead to suicide (Shneidman, 1993 ). In addition, repeated exposures to workplace bullying may cause a series of neuroendocrine and immunological changes, including increased activity of the hypothalamic–pituitary–adrenal axis and sympathetic nervous system (Reader et al, 2015 ; Rajalingam et al, 2021 ). Such repeated exposures may also elevate inflammatory markers (Jacobsen et al, 2018 ; Rajalingam et al, 2020 ), which may facilitate individual engagement in suicide ideation and attempts (Ernst et al, 2009 ; Van Heeringen & Mann, 2014 ).…”

Counteracting Workplace Bullying: A Qualitative Analysis of Employees’ Resistance Strategies Within the Service Industry

“…Workplace bullying results in depression, anxiety, low levels of self-esteem, and feelings of incompetence (Bernstein and Batchelor, 2002). In addition, workplace bullying has the capacity to trigger a neuro-immune mechanism causing severe anxiety and psychological consequences (Rajalingam et al, 2021), mental distress (Nielsen et al, 2020), insomnia (Nielsen et al, 2021), emotional exhaustion (Anasori et al, 2020), and psychological and post-traumatic stress disorders (Chenevert et al, 2022;Hong et al, 2022). Equivalently, the detrimental effects of bullying on organizational performance are significant.…”