2026-04-17T23:40:40Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/92342024-12-13T10:42:15Zcom_2072_378071com_2072_378040col_2072_378097

Premature T cell aging in major depression: A double hit by the state of disease and cytomegalovirus infection Simon, Maria S. Ioannou, Magdalini Arteaga Henriquez, Gara Wijkhuijs, Annemarie Berghmans, Raf Musil, Richard Institut Català de la Salut [Simon MS, Musil R] Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians-University, Munich, Germany. [Ioannou M] Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, GZ, Netherlands. [Arteaga-Henríquez G] Servei de Psiquiatria, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain. [Wijkhuijs A] Department of Immunology, Erasmus Medical Center, Rotterdam, GD, Netherlands. [Berghmans R] Advanced Practical Diagnostics BVBA, Turnhout, Belgium Vall d'Hebron Barcelona Hospital Campus Depressió psíquica Cèl·lules - Envelliment Infeccions per citomegalovirus PSYCHIATRY AND PSYCHOLOGY::Mental Disorders::Mood Disorders::Depressive Disorder::Depressive Disorder, Major PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Senescence DISEASES::Virus Diseases::DNA Virus Infections::Herpesviridae Infections::Cytomegalovirus Infections PSIQUIATRÍA Y PSICOLOGÍA::trastornos mentales::trastornos del humor::trastorno depresivo::trastorno depresivo mayor FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::senescencia celular ENFERMEDADES::virosis::infecciones por virus ADN::infecciones por Herpesviridae::infecciones por Citomegalovirus Childhood trauma; Major depressive disorder; T cytotoxic cell Trauma infantil; Trastorn depressiu major; cèl·lula T citotòxica Trauma infantil; Trastorno depresivo mayor; célula T citotóxica Introduction Previous research indicates that premature T cell senescence is a characteristic of major depressive disorder (MDD). However, known senescence inducing factors like cytomegalovirus (CMV) infection or, probably, childhood adversity (CA) have not been taken into consideration so far. Objective Differentiation and senescent characteristics of T cells of MDD patients were investigated in relation to healthy controls (HC), taking the CMV seropositivity and CA into account. Methods 127 MDD and 113 HC of the EU-MOODSTRATIFICATION cohort were analyzed. Fluorescence activated cell sorting (FACS) analysis was performed to determine B, NK, and T cell frequencies. In a second FACS analysis, naïve, effector memory (Tem), central memory (Tcm), effector memory cells re-expressing RA (TEMRA), as well as CD28+ and CD27+ memory populations, were determined of the CD4+ and CD8+ T cell populations in a subsample (N = 35 MDD and N = 36 HC). CMV-antibody state was measured by IgG ELISA and CA by the Childhood Trauma Questionnaire. Results We detected a CMV-antibody positivity in 40% of MDD patients (35% HC, n. s.) with seropositive MDD cases showing a higher total childhood trauma score. Second, a higher inflation of memory CD4+ T helper cells in CMV seronegative patients as compared to seronegative HC and reduced numbers of naïve CD4+ T helper cells in CMV seropositive patients (not in CMV seropositive HC) were found. Third, a higher inflation of memory CD8+ T cytotoxic cells in CMV seropositive cases as compared to CMV seropositive HC, particularly of the TEMRA cells, became apparent. Higher percentages of CD4+ TEMRA and late stage CD27−CD28− TEMRA cells were similar in both HC and MDD with CMV seropositivity. Overall, apportioning of T cell subpopulations did not differ between CA positive vs negative cases. Conclusions MDD patients show several signs of a CMV independent “MDD specific” premature T cell aging, such as a CMV independent increase in CD4+ T memory cells and a latent naïve CD4 T-cell reduction and a latent CD8+ T-cell increase. However, these two latent T cell senescence abnormalities only become evident with CMV infection (double hit). This work was supported by the European Commission: EU 7th Framework program (grant number EU-FP7-CP-IP-2008-222963) and Horizon 2020 (grant number H2020-SC1-2016-2017/H2020-SC1-2017-Two-Stage-RTD) grants were received by HAD, Erasmus Medical Center Rotterdam. The funding source had no role in the study design, the data collection, the analysis and interpretation of data, the manuscript writing, and in the decision to submit the article for publication. 2023-03-23T13:13:12Z 2023-03-23T13:13:12Z 2023-05 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Simon MS, Ioannou M, Arteaga-Henríquez G, Wijkhuijs A, Berghmans R, Musil R, et al. Premature T cell aging in major depression: A double hit by the state of disease and cytomegalovirus infection. Brain Behav Immun Health. 2023 May;29:100608. 2666-3546 https://hdl.handle.net/11351/9234 10.1016/j.bbih.2023.100608 36909830 http://hdl.handle.net/11351/9234 eng Brain, Behavior, & Immunity - Health;29 https://doi.org/10.1016/j.bbih.2023.100608 info:eu-repo/grantAgreement/EC/FP7/222963 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Elsevier Scientia