Meta-Analysis of Lymphocytes in Schizophrenia: Clinical Status and Antipsychotic Effects

Background: Schizophrenia is associated with immune system dysfunction, including abnormal blood immune cell parameters. We performed a meta-analysis of these associations, considering the effect of clinical status and antipsychotic treatment following an acute exacerbation of psychosis. Methods: We identified articles by searching PubMed, PsycINFO, and Thomson Reuters (formerly ISI) Web of Knowledge and the reference lists of identified studies. Results: Sixteen studies of blood lymphocytes met the inclusion criteria. There was insufficient data for a meta-analysis of the mononuclear phagocytic system. In cross-sectional studies, there was a significant increase in the CD4% and CD56% in acutely relapsed inpatients. Absolute levels of total lymphocytes, CD3, and CD4, and the CD4/CD8 ratio were significantly increased, and the CD3% was significantly decreased in drug-native first-episode psychosis. In longitudinal studies, the CD4/CD8 ratio appeared to be state-related markers, as it decreased following antipsychotic treatment for acute exacerbations of psychosis. Absolute CD56 levels appeared to be a trait marker, as levels significantly increased following antipsychotic treatment for relapse. Conclusions: Blood lymphocyte abnormalities in drug-naive first-episode psychosis suggest an effect that may be independent of antipsychotic medications. While some parameters (CD4/CD8) may be state markers for acute exacerbations of psychosis, others (CD56) may be trait markers; however, more longitudinal studies are needed. Although these findings could provide the basis for future hypothesis testing, a relatively small number of studies and subjects, lack of correlative data with clinical features, and inadequate consideration of potential confounding factors limit the results.