title: Sex differences in cortisol response to corticotropin releasing hormone challenge over puberty: Pittsburgh Pediatric Neurobehavioral Studies.
abstract: OBJECTIVE
  Consistent sex differences in regulation of the hypothalamic pituitary adrenocortical (HPA) axis have been shown in animal models and emerge over puberty. However, parallel work in humans is lacking despite implications for elucidating the emergence of sex differences in depression over puberty. We investigated sex differences in HPA response to corticotropin releasing hormone (CRH) challenge over puberty in a carefully screened normative sample.
  
  
  METHODS
  Participants were 68 healthy children (41% girls), ages 6-16, with no personal or family history of psychiatric disorder. Pubertal maturation was determined by Tanner staging. Following 24h of adaptation, 9-10 plasma cortisol samples were collected over 30-40 min pre-infusion baseline, 1 μg/kg CRH infusion, and 90-180 min post-infusion recovery. Thirty-seven participants completed 2+ CRH challenges allowing inclusion of cross-sectional and longitudinal data in all analyses. The influence of gender and pubertal maturation on parameters of cortisol response to CRH challenge was investigated using nonlinear mixed model methodology.
  
  
  RESULTS
  Girls showed increasing total cortisol output following CRH challenge over puberty, while boys showed little change in total cortisol output over puberty. Increased cortisol output in girls was explained by slower reactivity and recovery rates leading to prolonged time to reach peak cortisol and delayed return to baseline over puberty. Girls also showed increasing baseline cortisol over puberty, while boys showed declining baseline over puberty.
  
  
  CONCLUSIONS
  Results reveal subtle normative sex differences in the influence of pubertal maturation on HPA regulation at the pituitary level. This normative shift may tip the balance towards stress response dysregulation in girls at high risk for depression, and may represent one potential mechanism underlying elevated rates of depression among pubescent girls.
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Alpert Medical School and The Miriam Hospital, Providence, RI 02903, United States. lstroudri@gmail.com
authors.forename: Laura R
authors.initials: LR
authors.lastname: Stroud
authors.forename: George D
authors.initials: GD
authors.lastname: Papandonatos
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Williamson
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Dahl
mesh_terms: D000293:Adolescent; D002648:Child; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D009483:Neuropsychological Tests; D010372:Pediatrics / Q000379:methods; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011627:Puberty / Q000187:drug effects* / Q000378:metabolism; D012107:Research Design; D012727:Sex Characteristics
chemical_list: D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone