A meta-analysis of peripheral blood nerve growth factor levels in patients with schizophrenia

Abstract

Neurotrophins particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are crucial modulators in the neurodevelopment and maintenance of central and peripheral nervous systems. Neurotrophin hypothesis of schizophrenia (SCZ) postulated that the changes in the brains of SCZ patients are the result of disturbances of developing processes involving neurotrophic factors. This hypothesis was mainly supported by the abnormal regulation of BDNF in SCZ, especially the decreased peripheral blood BDNF levels in SCZ patients validated by several meta-analyses. However, the regulation of NGF in SCZ remains unclear because of the inconsistent findings from the clinical studies. Therefore, we undertook, to the best of our knowledge, the first systematic review with a meta-analysis to quantitatively summarize the peripheral blood NGF data in SCZ patients compared with healthy control (HC) subjects. A systematic search of Pubmed, PsycINFO and Web of Science identified 13 articles encompassing a sample of 1693 individuals for the meta-analysis. Random-effects meta-analysis showed that patients with SCZ had significantly decreased peripheral blood levels of NGF when compared with the HC subjects (Hedges’s g=−0.633, 95% confidence interval (CI)=−0.948 to −0.318, P<0.001). Subgroup analyses revealed reduced NGF levels both in serum (Hedges’s g=−0.671, 95% CI=−1.259 to −0.084, P=0.025) and plasma (Hedges’s g=−0.621, 95% CI=−0.980 to −0.261, P<0.001) of the patients, and in drug-free (Hedges’s g=−0.670, 95% CI=−1.118 to −0.222, P=0.003) and medicated (Hedges’s g=−0.357, 95% CI=−0.592 to −0.123, P=0.003) patients with SCZ. Furthermore, meta-regression analyses showed that age, gender and sample size had no moderating effects on the outcome of the meta-analysis, whereas disease severity might be a confounding factor for the meta-analysis. These results demonstrated that patients with SCZ are accompanied by the decreased peripheral blood NGF levels, strengthening the clinical evidence of an abnormal neurotrophin profile in the patients with SCZ.

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Acknowledgements

This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, USA, and the Minzu University Research Fund (ydzxxk201619&18, 2016SHXY01) and the 111 Project of China (B08044).

Author contributions

X-YQ and YC conceived and designed the study; CC and H-TW collected the data. X-YQ, CC, H-TW and YC analyzed and interpreted the data. YC drafted the manuscript with critical revisions from all the authors.

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Correspondence to Y Cheng.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website

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