T-cell subset phenotypes in patients with bipolar disorder or schizophrenia with history of childhood maltreatment

Abstract

Introduction: History of Childhood Maltreatment (CM) has repeatedly been associated with an increased risk of developing bipolar disorders (BD) or schizophrenia (SZ). The impact of severe stress induced by CM is thought to be mediated by increased inflammation reflected by deregulated levels of circulating pro- and anti-inflammatory cytokines. However, little is known about the potential impact of exposition to CM on lymphocyte subpopulations or the role of pre-existing infections on the impact of CM. We thus explored the role of CM and the impact of past exposure to infections on lymphocyte subpopulation.as these could be important avenues to better understand the impact of severe stress in major mood and psychotic disorders. Patients and Methods: 118 adult patients with SZ and 152 with BD were included in the analysis. History of CM was assessed using the Childhood Trauma Questionnaire (CTQ), current and past psychiatric symptomatology were evaluated. Circulating lymphocytes subsets were analyzed using flow cytometry-based analysis. Past exposure to common infectious stigma including toxoplasma, Cytomegalovirus (CMV) and Ebstein-Barr Virus (EBV) were measured by solid phase-enzyme microplate and ELISA immunoassays. Relationship between CM, biological phenotypes and clinical phenotypes were analyzed using univariate and multivariate analyses. Results: We found that patients with BD and CM, as compared to those without, had higher levels of CD3+CD8+ cytotoxic T cells and CMV antibodies along decreased levels of CD45RA+CCR7+CD8+ naïve CD8 T cells, and a more severe clinical profile. We also observed that levels of CMV antibodies were inversely associated with the CD3+CD8+ lymphocyte subset level.Patients with SZ and CM have decreased levels of CD14+ monocytes. Accumulation of types of maltreatment is associated with increased Body Mass Index and CMV autoantibodies as well as decreased levels of CD14+ monocytes. Conclusion: We observed that adult patients with BD or SZ having been exposed to CM exhibit specific immune cell subset profiles, clinical features and stigma of past infections. Altogether, our findings, especially in the context of BD, allows us to suggest a possible interplay between CM and CMV infectious events possibly inducing premature aging and cellular senescence, two events already known to be associated with psychiatric conditions. Longitudinal studies of patients exposed to maltreatment are warranted to replicate, predict and anticipate the specific needs of these patients.