Value of peripheral neurotrophin levels for the diagnosis of depression and response to treatment: A systematic review and meta-analysis

•Changed peripheral BDNF, NGF, IGF-1, VEGF, and S100B levels are strongly associated with pathogenesis MDD.•Peripheral S100B is associated with antidepressant treatment response in MDD.•Peripheral BDNF levels can be used to assess the response of antidepressant treatment.•Peripheral VEGF levels are significantly increased in responders after antidepressant treatment. The neurotrophin hypothesis indicates that neurotrophic factors are important for the pathophysiology of major depressive disorder (MDD), with alterations in peripheral neurotrophin levels having potential clinical application for MDD. The present meta-analysis aimed to investigate the diagnostic value for MDD of peripheral neurotrophin levels in cross-sectional studies and the association between peripheral neurotrophin levels and the response to antidepressant treatment in longitudinal studies. Published studies in the PubMed and Web of Science databases were systematically searched up to February 2020. The search terms included depressive disorder, neurotrophic factor, serum/plasma and their synonyms. Human studies reporting on BDNF, GDNF, IGF-2, VEGF, NGF, FGF-2, and S100B levels in MDD patients were included. Data comparing MDD patients and healthy controls, and/or between responders and non-responders before and after antidepressant treatment were extracted. A random effects model was used to calculate standardized mean differences. A total of 177 original studies were identified, including 139 cross-sectional and 38 longitudinal studies. Significantly reduced BDNF and NGF levels and significantly elevated IGF-1, VEGF, and S100B levels were reported in MDD patients compared with healthy controls, while GDNF and FGF-2 levels were not significantly different. Furthermore, compared with non-responders, S100B levels at baseline and BDNF levels following treatment were significantly elevated in responders. In addition, there was a significantly elevated level of VEGF after treatment in responders only. In conclusions, alterations in peripheral neurotrophins levels were strongly associated with the biology and the treatment response of MDD. Further investigations are required to examine potential sources of heterogeneity.