Associations between T cells and attention problems in the general pediatric population: The Generation R study

Abstract

Objective:The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) is currently unclear. We hypothesized that chronic immune activation, as indexed by T and B cells, plays a role in the pathophysiology of attention problems. Therefore, we examined T and B cell subsets in a general pediatric population with information on attention problems. Methods:We included 756 10-year-old children from the Generation R populationbased cohort. Eleven-color flow cytometry was performed on peripheral blood samples to determine T and B cell subsets. The Child Behavior Checklist rated by parents was used to measure attention problems. Data were analyzed using linear regression analyses, adjusting for maternal and child covariates and co-occurring childhood psychopathology.Results: For T helper 1 (Th1) cells, one standard deviation (SD) increase was associated with 5.3% (95%CI 0.3; 10.5) higher attention problem scores. Furthermore, 1SD increase in CD8 + T cells was associated with 7.5% (95%CI 2.4; 12.7) higher attention problem scores. Within total CD8 + T cells, 1SD increase in naive or central memory cells was associated with 6.9% (95%CI 2.0; 12.1) and 6.4% (95%CI 1.5; 11.6) higher attention problem scores, respectively. No associations between Th2, Treg or B memory cells and attention problem scores were observed. Conclusion:Higher Th1 and cytotoxic T cell numbers are associated with higher attention problem scores independent of co-occurring psychopathology. This might indicate a possible role of a pro-inflammatory immune profile in childhood attention problems.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study

“…The presence of CD8+ lymphocytes is indicative of the onset of autoimmune mental and neurological conditions in pediatric acute-onset neuropsychiatric syndrome (PANS), predominantly diagnosed with ADHD ( 52 ). Childhood attention problems are heavily influenced by the pro-inflammatory immune spectrum, where an increased count of Th1 and cytotoxic T cells correlates with elevated attention problem scores, independent of simultaneous psychopathological conditions ( 53 ). Among all CD8 T cells, an elevation of 1SD in either naive or central memory cells correlated with an increase of 6.9% (95%CI: 2.0~12.1) and 6.4% (95%CI: 1.5~11.6) in scores for attention problems ( 53 ).…”

“…Childhood attention problems are heavily influenced by the pro-inflammatory immune spectrum, where an increased count of Th1 and cytotoxic T cells correlates with elevated attention problem scores, independent of simultaneous psychopathological conditions ( 53 ). Among all CD8 T cells, an elevation of 1SD in either naive or central memory cells correlated with an increase of 6.9% (95%CI: 2.0~12.1) and 6.4% (95%CI: 1.5~11.6) in scores for attention problems ( 53 ). The function of NKT cells in enhancing CD8 T-cell reactions and memory development in immunization, pathogenic infections, and tumor immunity in both mice and humans has been extensively studied ( 54 , 55 ).…”

Assessment of the natural killer cell, IFN-ƒ× and IL-10 blood levels in children with attention-deficit/hyperactivity disorder

“…7 Several immunological mechanisms, such as the brain's primary immune cells; glial cells, which are essential for synaptic pruning throughout neurodevelopment, and numerous immune signaling molecules, including cytokines and complement proteins, were shown to regulate and alter neurogenesis. 8 Microglia are the brain's primary resident immune cells. Microglial cells, when activated, emit pro-inflammatory cytokines and other substances including glutamate, which contribute to neuroinflammation.…”