Department of Psychiatry, Dokuz Eylul University Medical School, Izmir 35340, Turkey.
Department of Neuroscience, Dokuz Eylul University, Izmir 35340, Turkey.
Psychol Med. 2019 Sep;49(12):1971-1979. doi: 10.1017/S0033291719001685. Epub 2019 Jul 9.
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.
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.
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.
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.
精神分裂症与明显的认知障碍有关。然而，精神分裂症认知功能障碍的病理生理机制仍不清楚。脑源性神经营养因子（BDNF）和 C 反应蛋白（CRP）是精神分裂症中最常研究的认知的外周标志物。
对 PubMed 和 Scopus 数据库进行了系统综述，评估了精神分裂症认知障碍、CRP 和 BDNF 水平之间的关系，检索时间截至 2019 年 1 月 31 日。采用随机效应荟萃分析。
本荟萃分析共纳入 21 项研究，共包括 2449 例精神分裂症谱系障碍患者。总的来说，BDNF（r=0.12，CI0.04-0.19）和 CRP（r=-0.13，CI0.08-0.18）水平与精神分裂症患者的认知功能均有轻度但显著的相关性（r=0.12，CI0.04-0.19）。在认知领域的荟萃分析中，BDNF 水平与言语记忆（r=0.16，CI0.09-0.23）、工作记忆（r=0.14，CI0.06-0.22）、处理速度（r=0.18，CI0.10-0.26）和言语流畅性（r=0.09，CI0-0.18）呈显著相关。CRP 水平升高与所有认知领域均相关（r=-0.09 至-0.13），但与流畅性无关。亚组分析表明，在慢性样本中，认知和 BDNF 水平之间的关系更为显著。
目前的研究结果表明，精神分裂症患者的认知障碍与 CRP 升高和 BDNF 水平降低显著相关，尤其是在慢性样本中。然而，这些相关性的效应量较小，表明炎症和 BDNF 水平降低在大多数精神分裂症患者的认知功能障碍中不起主要作用。需要进一步研究来探讨可能影响精神分裂症中炎症、神经营养因子和认知之间关系水平的中介和混杂因素。
