Salivary cytokine cluster moderates the association between caregivers perceived stress and emotional functioning in youth

Brain Behav Immun. 2021 May;94:125-137. doi: 10.1016/j.bbi.2021.02.025. Epub 2021 Mar 2.


Some individuals exposed to early life stress show evidence of enhanced systemic inflammation and are at greater risk for psychopathology. In the current study, caregivers and their offspring (0-17 years) were recruited at a pediatric clinic visit at the University of California, San Francisco (UCSF). Mothers and seven-year-old children from the Growing Up inSingaporeTowards healthy Outcomes (GUSTO) prospective birth cohort were used as a replication cohort. Caregivers perceived stress was measured to determine potential intergenerational effects on the children's functioning and inflammation levels. Children's emotional functioning in the UCSF cohort was evaluated using the Pediatric Quality of Life (PedsQL) inventory. Child emotional and behavioral functioning was measured using the Child Behavior Checklist (CBCL) in GUSTO. Saliva was collected from the children and salivary levels of IL-6, IL-1β, IL-8 and TNF-α were measured using an electrochemiluminescent cytokine multiplex panel. Child IL-6, IL-1β, IL-8 cytokine levels were clustered into low, average, and high cytokine cluster groups using hierarchical cluster analysis. We did not find that salivary cytokine clusters were significantly associated with children's emotional or behavioral function. However, cytokine clusters did significantly moderate the association between increased caregiver perceived stress and reduced child emotional functioning (UCSF cohort) and increased Attention-Deficit-Hyperactivity (ADH) problems (GUSTO cohort, uncorrected Cohen's F2 = 0.02). Using a cytokine clustering technique may be useful in identifying those children exposed to increased caregiver perceived stress that are at risk of emotional and attention deficit hyperactivity problems.

Keywords: Attention deficit hyperactivity (ADH); Caregiver perceived stress; Cytokines; Depression; Emotional functioning; Hierarchical cluster analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adolescent Health
  • Caregivers*
  • Child
  • Child Health
  • Child, Preschool
  • Cytokines*
  • Emotions*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Mental Health
  • Prospective Studies
  • Quality of Life
  • Saliva
  • Stress, Psychological*


  • Cytokines