Meta-analysis of lymphocytes in schizophrenia: clinical status and antipsychotic effects

Abstract

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-naïve 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.

Figure 1. Immune Cell Parameters in Schizophrenia by Clinical Status

Effect size estimates and 95% CIs for immune cell parameters in cross-sectional studies of acute relapse of psychosis (AR) and drug-naive first-episode psychosis (FEP) versus controls are represented by red and blue bars and error bars, respectively. For AR and FEP, positive effect sizes (bars going to the right) indicate that the parameter was higher in schizophrenia than controls; negative effect sizes (bars going to the left) indicate that levels were higher in controls than in patients with schizophrenia. Similarly, green bars and error bars represent effect size estimates and 95% CIs for the change in levels of immune parameters in longitudinal studies following antipsychotic treatment for an acute exacerbation of psychosis. Positive effect sizes (bars going to the right) indicate that the parameter increased following antipsychotic treatment for acute psychosis; negative effect sizes (bars going to the left) mean that the parameter decreased following antipsychotic treatment. Error bars that exclude 0 are significant at the p<0.05 level.