PMID- 28664925
OWN - NLM
STAT- MEDLINE
DCOM- 20180516
LR  - 20181113
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 42
IP  - 11
DP  - 2017 Oct
TI  - Evidence for Immune Activation and Resistance to Glucocorticoids Following 
      Childhood Maltreatment in Adolescents Without Psychopathology.
PG  - 2272-2282
LID - 10.1038/npp.2017.137 [doi]
AB  - Early-life stress (ELS) increases the risk for psychopathology. Immune and 
      endocrine changes have been reported in adults and are associated with 
      maladaptation of stress-responsive systems. Here we investigated the effects of 
      ELS on endocrine and immune pathways in adolescents without psychopathology. 
      Thirty adolescents with a history of childhood maltreatment and 27 adolescents 
      without ELS history were recruited. Blood and hair samples were obtained from all 
      participants. Lymphocytes were isolated and stimulated in vitro. Flow cytometry 
      was used to evaluate lymphocyte subsets, Th1/Th2/Th17 cytokines, 
      mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-kappaB) 
      signaling pathways, as well as lymphocyte sensitivity to dexamethasone. 
      Brain-derived neurotrophic factor (BDNF) and hair cortisol were assessed with 
      enzyme-linked immunosorbent assays (ELISAs). Adolescents with a history of ELS 
      had increased percentages of T-cell activation markers (CD3+CD4+CD25+ and 
      CD3+CD69+) and senescent T cells (CD8+CD28- and CD4+CD28-), as well as decreased 
      percentages of NK (CD3-CD56+) and NK T cells (CD3+CD56+). Following stimulation, 
      lymphocytes of ELS+ adolescents produced significantly more IL-2, IL-4, IFN-gamma, 
      and IL-17 and engaged more MAPK ERK and NF-kappaB signaling. ELS was associated with 
      increased hair cortisol levels in parallel with increased lymphocyte resistance 
      to dexamethasone and low plasma BDNF levels. These data provide the first 
      indication of the presence of immune activation and pro-inflammatory profiles in 
      healthy adolescents exposed to ELS, which could contribute to increased 
      vulnerability of trauma-related psychopathology later in life. The underlying 
      mechanisms of this impairment may include the enhanced activation of both MAPK 
      and NF-kappaB signaling in parallel to partial resistance to glucocorticoids.
FAU - do Prado, Carine Hartmann
AU  - do Prado CH
AD  - Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical 
      Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
FAU - Grassi-Oliveira, Rodrigo
AU  - Grassi-Oliveira R
AUID- ORCID: 0000-0001-9911-5921
AD  - Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical 
      Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
AD  - Developmental Cognitive Neuroscience Lab (DCNL), Brain Institute of Rio Grande do 
      Sul (InsCer), PUCRS, Porto Alegre, Brazil.
FAU - Daruy-Filho, Ledo
AU  - Daruy-Filho L
AD  - Developmental Cognitive Neuroscience Lab (DCNL), Brain Institute of Rio Grande do 
      Sul (InsCer), PUCRS, Porto Alegre, Brazil.
FAU - Wieck, Andrea
AU  - Wieck A
AD  - Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical 
      Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
FAU - Bauer, Moises Evandro
AU  - Bauer ME
AD  - Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical 
      Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
AD  - Faculty of Biosciences, PUCRS, Porto Alegre, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20170630
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytokines)
RN  - 0 (Glucocorticoids)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adolescent
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Child Abuse/psychology/*rehabilitation
MH  - Cytokines/*metabolism
MH  - Female
MH  - Glucocorticoids/*metabolism
MH  - Hair/metabolism
MH  - Humans
MH  - Hydrocortisone/metabolism
MH  - Lymphocytes/*metabolism
MH  - Male
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Signal Transduction/genetics/*physiology
PMC - PMC5603807
EDAT- 2017/07/01 06:00
MHDA- 2018/05/17 06:00
PMCR- 2018/10/01
CRDT- 2017/07/01 06:00
PHST- 2016/10/24 00:00 [received]
PHST- 2017/06/22 00:00 [revised]
PHST- 2017/06/24 00:00 [accepted]
PHST- 2017/07/01 06:00 [pubmed]
PHST- 2018/05/17 06:00 [medline]
PHST- 2017/07/01 06:00 [entrez]
PHST- 2018/10/01 00:00 [pmc-release]
AID - npp2017137 [pii]
AID - 10.1038/npp.2017.137 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2017 Oct;42(11):2272-2282. doi: 10.1038/npp.2017.137. 
      Epub 2017 Jun 30.