Peripheral inflammatory and neurotrophic biomarkers of cognitive impairment in schizophrenia: a meta-analysis

Background Schizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Brain-derived neurotrophic factor (BDNF) and C-reactive protein (CRP) are among the most commonly investigated peripheral markers of cognition in schizophrenia. Methods A systematic review in PubMed and Scopus databases was performed until 31 January 2019 to assess the relationship between cognitive impairment, CRP and BDNF levels in schizophrenia. A random-effects meta-analysis was conducted. Results Current meta-analysis included 21 studies including 2449 patients with schizophrenia-spectrum disorders. Overall, both BDNF [r = 0.12, confidence interval (CI) 0.04-0.19] and CRP (r = -0.13, CI 0.08-0.18) levels were very modestly but significantly related to cognitive functioning in schizophrenia (r = 0.12, CI 0.04-0.19). In meta-analyses of cognitive domains, BDNF levels were significantly associated with verbal memory (r = 0.16, CI 0.09-0.23), working memory (r = 0.14, CI 0.06-0.22), processing speed (r = 0.18, CI 0.10-0.26) and verbal fluency (r = 0.09, CI 0-0.18) performances. Elevated CRP levels were related to all cognitive domains (r = -0.09 to -0.13) except for fluency. Subgroup analyses suggested that the relationship between cognitive and BDNF levels were more pronounced in chronic samples. Conclusions Current findings suggest that cognitive impairment in schizophrenia is significantly related to elevated CRP and reduced BDNF levels in schizophrenia, particularly in chronic samples. However, small effect sizes of these correlations suggest that inflammation and decreased BDNF levels do not play a major role in cognitive dysfunction in most patients with schizophrenia. Further studies are needed to investigate the potential intermediating and confounding factors which can influence the level of relationship between inflammation, neurotrophic factors and cognition in schizophrenia.