Inflammatory Biomarkers Predictive of Psychopathology in Children With Physical Illness

While evidence shows that children with chronic physical illness are at increased risk for psychopathology, the causal mechanisms linking physical and mental illness early in life remain unconfirmed.

Given a lack of longitudinal studies investigating inflammatory responses in the context of child psychopathology, and none that specifically sample children with chronic physical illness, this study evaluated associations between inflammatory biomarkers and psychopathology in children with chronic physical illness over a 48-month period.

Data come from 128 children enrolled in the Multimorbidity in Children and Youth across the Life-course (MY LIFE) study who provided baseline dried blood samples for biomarker analysis and completed the 48-month assessment (mean age 11.0 years, 50.0% male). Psychopathology was measured using parent and child reports on the Emotional Behavioural Scales. Dried blood samples were assayed using the Bio-Plex 200 system. Linear mixed models, adjusted for age and sex, estimated associations between inflammatory biomarkers and child psychopathology over time.

No differences in biomarker concentrations across physical illnesses were found, except for interleukin (IL)-1β, which showed lower levels in the neurological subgroup (χ² = 13.27, p = 0.04). Elevated levels of granulocyte colony-stimulating factor (G-CSF) were associated with higher parent-reported internalizing symptoms (β = 0.09 [0.04]), whereas elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) was associated with child-reported (β = 1.83 [0.46]) and parent-reported total symptoms (β = 1.52 [0.69]), as well as child-reported internalizing (β = 1.35 [0.28]) and parent-reported externalizing symptoms (β = 0.72 [0.30]). Elevated IL-6 was associated with lower child-reported total symptoms (β = -0.87 [0.27]) and parent-reported externalizing symptoms (β = -0.35 [0.16]) over time.

Findings are not definitive evidence of a causal mechanism for physical-mental comorbidity in children but are consistent with reports in other populations. The predictive power of G-CSF, GM-CSF, and IL-6 supports the need for broader blood panels and routine mental health assessment, particularly for children on treatments that disrupt regulatory inflammatory pathways.