title: The longitudinal association of the diurnal cortisol rhythm with internalizing and externalizing problems in pre-schoolers. The Generation R Study.
abstract: BACKGROUND
  Studies investigating the association between diurnal cortisol rhythm and behavioural problems in young children have yielded inconsistent results. We tested the hypothesis that variations in diurnal cortisol rhythm in pre-schoolers are already related to problem behaviour early in life with a cross-sectional and longitudinal design.
  
  
  METHODS
  This study was embedded in Generation R, a population-based cohort from foetal life onwards. Parents collected saliva samples from their infant at 5 moments during 1 day. In 322 infants aged 12-20 months, we determined the diurnal cortisol rhythm by calculating the area under the curve (AUC), the cortisol awakening response (CAR), and the diurnal slope. Problem behaviour was assessed at ages 1.5 and 3 years with the Child Behavior Checklist/1.5-5 years.
  
  
  RESULTS
  No cross-sectional associations between the cortisol composite measures and problem behaviour were found at 1.5 years. However, cortisol predicted change in internalizing problems as assessed from 1.5 to 3 years, but not change in externalizing problems. Children with higher AUC levels, flatter slopes and a more positive CAR at baseline were more likely to score higher on the Internalizing Problems scale (β per nmol/L AUC: 0.08, 95% CI: 0.00; 0.17, p=0.04; β per nmol/L/h slope: 0.57, 95% CI: 0.17; 0.98, p=0.006; β per nmol/L CAR: 0.04, 95% CI: 0.01; 0.08, p=0.02) at follow-up.
  
  
  CONCLUSIONS
  Variations in diurnal cortisol rhythm are associated with change in internalizing problems in pre-schoolers. The results suggest that variations in diurnal cortisol patterns early in life precede internalizing problems.
authors.affiliation: The Generation R Study Group, Erasmus MC-University Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Nathalie S
authors.initials: NS
authors.lastname: Saridjan
authors.affiliation: The Generation R Study Group, Erasmus MC-University Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Fleur P
authors.initials: FP
authors.lastname: Velders
authors.affiliation: The Generation R Study Group, Erasmus MC-University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands; Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands. Electronic address: h.tiemeier@erasmusmc.nl.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
mesh_terms: D002653:Child Behavior Disorders / Q000175:diagnosis* / Q000503:physiopathology; D002675:Child, Preschool; D002940:Circadian Rhythm / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012463:Saliva / Q000737:chemistry
chemical_list: D006854:Hydrocortisone
keywords: Cohort; Cortisol; Diurnal rhythm; HPA axis; Infants; Longitudinal; Problem behaviour