The Association between the Immune Proteome and Brain Function and Socioemotional Development in 5-Year-Old Children

Early childhood, especially the age of five, represents a critical developmental period of rapid brain and socioemotional development. Despite growing evidence of immune processes in brain development, most research has focused on prenatal exposure or adult populations and has examined a limited number of classical inflammatory markers. Therefore, the broader relationship between the peripheral immune system, functional brain organization, and socioemotional development in young children remain unexplored. This thesis aimed to explore associations between the peripheral immune proteome, functional brain connectivity, and socioemotional functioning in typically developing 5-year-old children. A multidisciplinary, cross-sectional approach was used, by integrating socioemotional assessments using Strengths and Difficulties Questionnaire (SDQ), immune proteomics, and functional magnetic resonance imaging (fMRI) in 5-year-old children from the FinnBrain Birth Cohort Study. Associations between immune proteome and both socioemotional functioning and brain connectivity were examined using data-driven feature selection methods. This included partial correlation analysis and elastic net regression, which were used to identify candidate immune proteins. Associations with brain function were examined using functional connectome harmonics entropy to capture global connectivity patterns, and voxel-wise analyses of regional homogeneity (ReHo) to assess local functional connectivity. Data-driven analyses identified HSD11B1 as showing the strongest association with socioemotional functioning. Notably, the commonly studied inflammatory markers from prior literature, on the other hand, demonstrated no significant associations. fMRI analyses identified TNFRSF11B, VEGFD, CCL4, CCL26 and AGER from which TNFRSF11B showed most robust associations with global functional network organization. Voxel-wise analyses further revealed TNFRSF11B and CCL26 to be negatively associated with local functional connectivity within frontal and cerebellar regions. These results demonstrate novel links between the immune proteome, brain function and socioemotional development, indicating that immune-brain associations in early childhood are selective and pathway-specific, extending beyond classical inflammatory markers. While these findings reflect a distributed influence on normative brain development, they remain associative rather than causal due to cross-sectional study design and should be replicated and further examined in longitudinal studies to clarify underlying mechanisms and developmental trajectories.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2026

Author dc:creator

• Lahtela, Noora

• Immune proteome
• Neurodevelopment
• Functional connectivity
• Socioemotional development
• Early childhood
• Neuroimmune interactions

Statement dc:rights

• In Copyright 1.0

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/634468

OAI identifier oai:identifier

oai:helda.helsinki.fi:10138/634468