Authors
Haixia Zheng, Bart Ford, Lily A Heritage, Ebrahim Haroon, Wesley K Thompson, Chun Chieh Fan, T Kent Teague, Martin P Paulus, Jonathan Savitz, Steve Cole
Published in
Brain, behavior, and immunity. Pages 107015. Sep 18, 2026. Epub Sep 18, 2026.
Abstract
Cytomegalovirus (CMV) establishes lifelong infection and promotes an immunosenescent T cell profile characterized by depletion of naïve cells and expansion of terminally differentiated effector memory cells re-expressing CD45RA (TEMRA). We examined whether CMV-related T cell differentiation was associated with brain structure and depressive symptoms in two complementary cohorts. In a neuroimaging cohort of 129 adults, higher CD4+ TEMRA percentages was associated with lower parahippocampal volume (β = -0.27, 95% CI [-0.42, -0.11], pFDR = 0.022). However, no T cell measure significantly mediated the association between CMV serostatus and parahippocampal volume after FDR correction. In a population-based sample of 5,759 older adults from the Health and Retirement Study, higher CD4+ TEMRA:naïve ratios, reflecting relative expansion of TEMRA cells and depletion of naïve CD4+ T cells, were associated with greater depressive symptom severity across three assessments from 2016 to 2020 (β = 0.097, 95% CI [0.074, 0.119], pFDR < 0.001). Structural equation models indicated significant indirect associations between CMV seropositivity and depressive symptoms through the CD4+ TEMRA:naïve ratio and CD4+ naïve cells. These findings link CMV-related T cell differentiation to reduced parahippocampal volume and increased depressive symptoms. Larger longitudinal studies integrating immunophenotyping, neuroimaging, and clinical outcomes in the same participants are needed to test this proposed pathway.
PMID:
42759819
Bibliographic data and abstract were imported from PubMed on 19 Sep 2026.
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