Plasma adiponectin levels in schizophrenia and role of second-generation antipsychotics: a meta-analysis

Psychoneuroendocrinology. 2015 Jun:56:179-89. doi: 10.1016/j.psyneuen.2015.03.012. Epub 2015 Mar 14.


Background: People with schizophrenia are more likely than general population to suffer from metabolic abnormalities, with second-generation antipsychotics (SGAs) increasing the risk. Low plasma adiponectin levels may lead to metabolic dysregulations but evidence in people with schizophrenia, especially for the role of SGAs, is still inconclusive.

Objective: To compare plasma adiponectin levels between people with schizophrenia and healthy controls, and to estimate the relative effect of schizophrenia and SGAs on adiponectin.

Methods: We performed a systematic review and meta-analysis of observational studies published up to 13 June 2014 in main electronic databases. Pooled standardized mean differences (SMDs) between index and control groups were generated. Appropriate subanalyses and additional subgroup analyses were carried out.

Results: Data from 2735 individuals, 1013 with and 1722 without schizophrenia, respectively, were analysed. Schizophrenia was not associated with lower adiponectin levels (SMD of -0.28, 95%CI: -0.59, 0.04; p=0.09). However, individuals with schizophrenia taking SGAs had plasma levels significantly lower than controls (p=0.002), which was not the case of drug free/drug naïve subjects (p=0.52). As regards single antipsychotic drugs clozapine (p<0.001) and olanzapine (p=0.04)--but not risperidone (p=0.88)--were associated with adiponectin levels lower than controls.

Conclusions: People with schizophrenia per se may not have levels of adiponectin lower than controls, though treatment with SGAs is associated with this metabolic abnormality. This bears clinical significance because of hypoadiponectinemia involvement in cardiovascular diseases, even if mechanisms whereby SGAs affect adiponectin remain unexplained. Longitudinal studies evaluating long-term effects of SGAs on adiponectin are needed.

Keywords: Adiponectin; Cardiovascular diseases; Metabolic abnormalities; Schizophrenia; Second-generation antipsychotics; Weight gain.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adiponectin / blood*
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use*
  • Humans
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy*


  • Adiponectin
  • Antipsychotic Agents