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Inflammatory markers (IL-6 and CRP) in childhood and their association with brain structure and psychotic experiences

Kate Merritt1, Edward R Palmer2, Pedro Luque Laguna3

  • 1University College London, Division of Psychiatry, 4th Floor, Maple House, 149 Tottenham Court Road, London W1T 7BN, UK.

Brain, Behavior, and Immunity
|January 10, 2026
PubMed

Insights

Childhood inflammation, measured by C-reactive protein (CRP) and interleukin-6 (IL-6), impacts adult brain grey matter. Elevated CRP was linked to larger frontal gyrus volume in those with psychotic experiences, suggesting a psychosis-specific inflammatory pathway.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Immunology

Background:

  • Inflammation is a known risk factor for psychosis.
  • Childhood levels of C-reactive protein (CRP) and interleukin-6 (IL-6) are linked to increased risk of psychotic experiences (PEs) and disorders.
  • Mechanisms connecting inflammation and psychosis are not fully understood.

Purpose of the Study:

  • To investigate the association between childhood CRP and IL-6 levels and adult brain grey matter volume at age 20.
  • To determine if this association differs between individuals with and without PEs.
  • To explore potential disease-specific inflammatory pathways in psychosis.

Main Methods:

  • Utilized data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.
  • Acquired MRI scans at age 20 in participants with PEs (n=71) and controls (n=173).
  • Employed voxel-based morphometry to analyze the relationship between childhood inflammatory markers and adult grey matter volume, including interaction analyses based on PEs status.

Main Results:

  • Elevated childhood IL-6 was associated with smaller grey matter volume in several cortical regions (e.g., left supramarginal gyrus, right parahippocampal gyrus, left precuneus) in adulthood, regardless of PEs status.
  • A significant interaction between childhood CRP and PEs status was observed.
  • Elevated childhood CRP was associated with larger right superior frontal gyrus volume specifically in individuals with PEs, but not in controls.

Conclusions:

  • Childhood CRP levels influence adult grey matter volume differently based on the presence of PEs, suggesting a potential psychosis-specific inflammatory pathway.
  • Childhood IL-6 levels are associated with reduced grey matter volume in default mode network regions, indicating a more general effect on brain development irrespective of PEs.
  • Findings highlight the differential impact of specific inflammatory markers on brain structure in relation to psychosis risk.
Abstract

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