PMID- 34076732
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20240226
IS  - 1432-1246 (Electronic)
IS  - 0340-0131 (Print)
IS  - 0340-0131 (Linking)
VI  - 94
IP  - 8
DP  - 2021 Nov
TI  - Workplace bullying increases the risk of anxiety through a stress-induced 
      beta2-adrenergic receptor mechanism: a multisource study employing an animal model, 
      cell culture experiments and human data.
PG  - 1905-1915
LID - 10.1007/s00420-021-01718-7 [doi]
AB  - 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 
      beta(2)-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.
CI  - (c) 2021. The Author(s).
FAU - Rajalingam, Dhaksshaginy
AU  - Rajalingam D
AUID- ORCID: 0000-0002-4647-5437
AD  - Department of Psychosocial Science, University of Bergen, Bergen, Norway. 
      dhaksshaginy.rajalingam@uib.no.
FAU - Nymoen, Ingeborg
AU  - Nymoen I
AD  - National Institute of Occupational Health, Oslo, Norway.
FAU - Nyberg, Henriette
AU  - Nyberg H
AD  - National Institute of Occupational Health, Oslo, Norway.
FAU - Nielsen, Morten Birkeland
AU  - Nielsen MB
AD  - Department of Psychosocial Science, University of Bergen, Bergen, Norway.
AD  - National Institute of Occupational Health, Oslo, Norway.
FAU - Einarsen, Stale Valvatne
AU  - Einarsen SV
AD  - Department of Psychosocial Science, University of Bergen, Bergen, Norway.
FAU - Gjerstad, Johannes
AU  - Gjerstad J
AD  - Department of Psychosocial Science, University of Bergen, Bergen, Norway.
AD  - National Institute of Occupational Health, Oslo, Norway.
LA  - eng
GR  - 250127/The Norwegian Research council and the University of Bergen/
GR  - 237777/The Norwegian research council and the National Institute of Occupational 
      Health/
PT  - Journal Article
DEP - 20210602
PL  - Germany
TA  - Int Arch Occup Environ Health
JT  - International archives of occupational and environmental health
JID - 7512134
RN  - 0 (ADRB2 protein, human)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Anxiety/*genetics
MH  - Behavior, Animal
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Dexamethasone/pharmacology
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Models, Animal
MH  - Norepinephrine/blood/pharmacology
MH  - Occupational Stress/*psychology
MH  - Rats, Long-Evans
MH  - Rats, Sprague-Dawley
MH  - Receptors, Adrenergic, beta-2/*genetics
MH  - Social Interaction
MH  - Stress, Psychological/blood/genetics
MH  - Workplace/psychology
MH  - Young Adult
MH  - Rats
PMC - PMC8490242
OTO - NOTNLM
OT  - Anxiety
OT  - Bullying
OT  - Human
OT  - Rat
OT  - Social stress
OT  - rs1042714
COIS- The authors declare no conflicts of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/06/02
CRDT- 2021/06/02 12:22
PHST- 2020/11/19 00:00 [received]
PHST- 2021/03/23 00:00 [accepted]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/06/02 12:22 [entrez]
PHST- 2021/06/02 00:00 [pmc-release]
AID - 10.1007/s00420-021-01718-7 [pii]
AID - 1718 [pii]
AID - 10.1007/s00420-021-01718-7 [doi]
PST - ppublish
SO  - Int Arch Occup Environ Health. 2021 Nov;94(8):1905-1915. doi: 
      10.1007/s00420-021-01718-7. Epub 2021 Jun 2.