title: Glucocorticoid receptor pathway components predict posttraumatic stress disorder symptom development: a prospective study.
abstract: BACKGROUND
  Biological correlates of posttraumatic stress disorder (PTSD) have mostly been studied using cross-sectional or posttrauma prospective designs. Therefore, it remains largely unknown whether previously observed biological correlates of PTSD precede trauma exposure. We investigated whether glucocorticoid receptor (GR) pathway components assessed in leukocytes before military deployment represent preexisting vulnerability factors for development of PTSD symptoms.
  
  
  METHODS
  Four hundred forty-eight male soldiers were assessed before and 6 months after deployment to a combat zone. Participants were assigned to the PTSD or comparison group based on Self-Rating Inventory for PTSD scores after deployment. Logistic regression analysis was applied to predict development of a high level of PTSD symptoms based on predeployment GR number, messenger (m)RNA expression of GR target genes FKBP5, GILZ, and SGK1, plasma cortisol, and childhood trauma. We also investigated whether predeployment GR number and FKBP5 mRNA expression were associated with single nucleotide polymorphisms in the GR and FKBP5 genes, either alone or in interaction with childhood trauma.
  
  
  RESULTS
  Several GR pathway components predicted subsequent development of a high level of PTSD symptoms: predeployment high GR number, low FKBP5 mRNA expression, and high GILZ mRNA expression were independently associated with increased risk for a high level of PTSD symptoms. Childhood trauma also independently predicted development of a high level of PTSD symptoms. Additionally, we observed a significant interaction effect of GR haplotype BclI and childhood trauma on GR number.
  
  
  CONCLUSIONS
  Collectively, our results indicate that predeployment GR pathway components are vulnerability factors for subsequent development of a high level of PTSD symptoms.
authors.affiliation: Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van Zuiden
authors.forename: Elbert
authors.initials: E
authors.lastname: Geuze
authors.forename: Hanneke L D M
authors.initials: HL
authors.lastname: Willemen
authors.forename: Eric
authors.initials: E
authors.lastname: Vermetten
authors.forename: Mirjam
authors.initials: M
authors.lastname: Maas
authors.forename: Karima
authors.initials: K
authors.lastname: Amarouchi
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
mesh_terms: D054523:Adult Survivors of Child Abuse / Q000523:psychology*; D003130:Combat Disorders / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D006854:Hydrocortisone; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D014157:Transcription Factors; D000099159:Tacrolimus Binding Protein 5; C404226:TSC22D3 protein, human