title: Internalizing and externalizing behaviors predict elevated inflammatory markers in childhood.
abstract: BACKGROUND
  Children with behavior problems, such as internalizing or externalizing disorders, are at increased risk for poorer physical health in adulthood. Inflammation has been posited as a potential biological mediator underlying this association. However, it is unclear how early in development associations between behavior problems and inflammation may be detected, and whether associations are present for both internalizing and externalizing behaviors in pre-pubertal children.
  
  
  METHODS
  Using data from children in the Avon Longitudinal Study of Parents and Children, we examined associations between behavior problems at age 8 (assessed via the parent-report Strengths and Difficulties Questionnaire) and inflammatory markers assessed at age 10. Inflammatory markers included C-reactive protein (CRP; n=4069) and interleukin-6 (IL-6; n=4061). We further evaluated whether body mass index (BMI) mediated associations, and tested for potential reverse causality by considering whether age 10 inflammation was associated with changes from initial levels to age 12 behavior problems.
  
  
  RESULTS
  After adjusting for relevant covariates, age 8 externalizing behaviors were associated with elevated CRP at age 10, and age 8 internalizing and externalizing behaviors were associated with elevated IL-6 at age 10 (p's<0.05). We found no evidence that observed associations were mediated by BMI or that inflammatory markers at age 10 were associated with increased internalizing or externalizing behavior problems at age 12.
  
  
  CONCLUSIONS
  These findings document an association between behavior problems and elevated concentrations of CRP and IL-6 at 10 years. Heightened inflammation in childhood may be a pathway through which early behavior problems increase risk for adult chronic diseases.
authors.affiliation: Center on the Developing Child, Harvard University, Cambridge, MA, USA; Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Slopen
authors.forename: Laura D
authors.initials: LD
authors.lastname: Kubzansky
authors.forename: Karestan C
authors.initials: KC
authors.lastname: Koenen
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002652:Child Behavior / Q000502:physiology*; D002653:Child Behavior Disorders / Q000378:metabolism* / Q000523:psychology*; D004522:Educational Status; D005006:Ethnicity; D005260:Female; D006801:Humans; D007182:Income; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D007389:Internal-External Control; D008137:Longitudinal Studies; D008297:Male; D009035:Mothers; D012727:Sex Characteristics; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: Avon Longitudinal Study of Parents and Children (ALSPAC); Behavior problems; C-reactive protein; Externalizing behavior; Inflammation; Interleukin-6; Internalizing behavior