Early caregiving adversity is associated with elevated pro-inflammatory gene expression during adolescence

AI Summary

Adolescents with early caregiving adversity showed elevated pro-inflammatory NF-κB and reduced antiviral IRF transcription factor activity in circulating blood cells.
No group differences emerged on a priori downstream gene composites; differentially expressed transcripts originated mainly from CD16+ and CD16- monocytes.
Functional genomic RNA measures detect ELA-linked inflammatory regulation in adolescence and may be more sensitive than plasma proteins for early developmental trajectories.

TL;DR (AI Generated)

Though ELA has been consistently associated with elevated circulating markers of inflammation in varied adult populations, meta-analytic work has found mixed links between ELA and circulating protein markers of inflammation in adolescents, leaving the pathways by which the adult inflammatory phenotype emerges unclear.

Here we examined whether alterations in pro-inflammatory and Type I interferon (antiviral) gene expression in circulating immune cells (the Conserved Transcriptional Response to Adversity; CTRA) might provide a more sensitive measure of ELA-linked phenotypes in adolescents.

METHODS: We assessed pro-inflammatory (NF-κB) and anti-viral (Interferon Response Factor) transcription factor activity and downstream gene expression in peripheral blood samples from 18 internationally adopted youth who had experienced previous institutional caregiving (a profound form of ELA) and 34 comparison, non-adopted youth.

Basic summary

Brain Behav Immun. 2026 Nov 14:107270. doi: 10.1016/j.bbi.2026.107270. Online ahead of print.

ABSTRACT

BACKGROUND: Early life adversity (ELA) is thought to increase risk for poor health outcomes, in part through induction of a persistent pro-inflammatory phenotype. Though ELA has been consistently associated with elevated circulating markers of inflammation in varied adult populations, meta-analytic work has found mixed links between ELA and circulating protein markers of inflammation in adolescents, leaving the pathways by which the adult inflammatory phenotype emerges unclear. Here we examined whether alterations in pro-inflammatory and Type I interferon (antiviral) gene expression in circulating immune cells (the Conserved Transcriptional Response to Adversity; CTRA) might provide a more sensitive measure of ELA-linked phenotypes in adolescents.

RESULTS: Consistent with the CTRA, relative to comparison youth, youth with a history of ELA showed elevated pro-inflammatory (NF-κB) and decreased antiviral (IRF) transcription factor activity. We found no group differences on a priori downstream gene expression composites. Differentially expressed transcripts were preferentially derived from CD16 + and CD16- monocytes, responsible for coordinating the early inflammatory stages of immune responses.

CONCLUSIONS: These findings confirm ELA-linked inflammatory gene regulation in circulating blood cells during adolescence. Compared to plasma protein measures, functional genomic (RNA) measures of inflammation may provide more sensitive, early indexes of developmental trajectories of inflammation following adversity, prior to emergence of an adult ELA-linked inflammatory phenotype associated with disease.

PMID:43033945 | DOI:10.1016/j.bbi.2026.107270

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