title: Neuroendocrine and immunological correlates of chronic stress in 'strictly healthy' populations.
abstract: BACKGROUND
  Chronic stress has been associated with detrimental or maladaptive neuroendocrine and immunological changes.
  
  
  OBJECTIVE
  We assessed the neuroendocrine and immunological correlates of a realistic chronic stress experienced by strictly healthy caregivers of Alzheimer's disease patients and age-matched controls.
  
  
  METHODS
  We screened 330 caregivers and 206 non-caregivers according to the 'strictly healthy' conditions established by the SENIEUR protocol. Forty-one strictly healthy caregivers (60.56 +/- 16.56 years) and 33 non-stressed controls (60.27 +/- 14.11 years) were selected for this study. Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at multiple points by radioimmunoassay. Peripheral T cell proliferation and cellular sensitivity to glucocorticoids (corticosterone and dexamethasone, DEX) were evaluated by colorimetric assays. We also examined the hypothalamic-pituitary-adrenal (HPA) axis response to the administration of a low-dose DEX in vivo.
  
  
  RESULTS
  The caregivers were significantly more stressed, anxious and depressed than non-caregivers (all p < 0.0001), in contrast to similar cortisol levels. Caregivers had reduced DHEAS levels (-32%, p < 0.0001), an increased cortisol/DHEAS ratio (39.7%, p < 0.0001) and impaired HPA axis response to DEX intake. Caregivers had a higher T cell proliferation (p < 0.0001) and increased sensitivity to glucocorticoids in vitro (p < 0.01) as compared to non-stressed controls.
  
  
  CONCLUSIONS
  Our results suggest that the maintenance of health in chronically stressed populations may be associated with both protective and detrimental neuroendocrine and immunological changes.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Instituto de Pesquisas Biomédicas and Faculdade de Biociências, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Cristina M Moriguchi
authors.initials: CM
authors.lastname: Jeckel
authors.forename: Rodrigo P
authors.initials: RP
authors.lastname: Lopes
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Berleze
authors.forename: Clarice
authors.initials: C
authors.lastname: Luz
authors.forename: Leandro
authors.initials: L
authors.lastname: Feix
authors.forename: Irani Iracema de Lima
authors.initials: II
authors.lastname: Argimon
authors.forename: Lilian M
authors.initials: LM
authors.lastname: Stein
authors.forename: Moisés E
authors.initials: ME
authors.lastname: Bauer
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000451:nursing / Q000523:psychology; D001008:Anxiety Disorders / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D017028:Caregivers / Q000523:psychology*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D015331:Cohort Studies; D015897:Comorbidity; D003687:Dehydroepiandrosterone / Q000378:metabolism; D003866:Depressive Disorder / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D007107:Immune System / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000276:immunology* / Q000503:physiopathology; D013315:Stress, Psychological / Q000453:epidemiology* / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D005938:Glucocorticoids; D003687:Dehydroepiandrosterone; D006854:Hydrocortisone