title: Blunted HPA axis activity prior to suicide attempt and increased inflammation in attempters.
abstract: Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation is associated with increased risk for suicidal behavior. However, it is not clear whether such dysregulation exists prior to or is a consequence of attempt. Studies also show an activation of inflammatory responses in suicidal behavior but often combine attempters with those with ideation.
  
  
  
  The sample consisted of psychiatric inpatients, aged 15-30 years, admitted for suicide attempt (SA, n=38), inpatients admitted for suicidal ideation with no prior history of attempts (SI, n=40), and healthy controls (n=37). We compared SA, SI, and controls on hair cortisol concentrations (HCC), which provides retrospective levels of cortisol and thus prior to the attempt in SA. We also compared them on the expression of genes in the HPA axis and inflammatory pathways previously implicated in suicidal behavior (GR or NR3C1, SKA2, FKBP5, IL-1β, TNF-α); plasma C-Reactive Protein (CRP); and cellular measures of glucocorticoid receptor (GR) sensitivity and stimulated production of IL-6.
  
  
  
  We found lower HCC [β=-0.55, 95% CI (-0.96, -0.13), p=0.01, ES=-0.54] in first-time SA compared to SI and controls. In addition, SA showed lower GR or NR3C1 (α isoform) mRNA [β=-5.11, 95% CI (-10.9, 0.73), p=0.09, ES=-0.46], higher CRP [β=0.94, 95% CI (-0.004, 1.9), p=0.05, ES=0.60], and higher TNF-α mRNA [β=26.4, 95% CI (7.7, 45.2), p=0.006, ES=0.73].
  
  
  
  This is the first study to differentiate youth who attempt suicide from those with suicidal ideation on HCC and to show that low HCC precedes suicide attempt. Suicide attempters also showed a distinct biological profile on several markers in both the HPA axis and inflammatory pathways. Future longitudinal studies are needed to examine the ability of these biomarkers to predict suicidal behavior.
authors.affiliation: The Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: melhemnm@upmc.edu.
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Melhem
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Munroe
authors.affiliation: The Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Marsland
authors.affiliation: The Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Katarina
authors.initials: K
authors.lastname: Gray
authors.affiliation: The Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Brent
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Porta
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Antoine
authors.initials: A
authors.lastname: Douaihy
authors.affiliation: Department of Pscyhiatry, University of Colorado Denver Anschutz Medical Campus, Denver, CO, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Laudenslager
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: DePietro
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Rasim
authors.initials: R
authors.lastname: Diler
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Driscoll
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Gopalan
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006197:Hair / Q000737:chemistry; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D007297:Inpatients; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012189:Retrospective Studies; D059020:Suicidal Ideation; D013406:Suicide, Attempted; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein; D006854:Hydrocortisone
keywords: Gene expression; Hair cortisol; Ideation; Inflammation; Suicide attempt; Youth