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Background: Cognitive impairment is a core feature of disorders on the schizophrenia-bipolar spectrum, i.e., schizophrenia, bipolar disorder, and schizoaffective disorder. Brain-derived neurotrophic factor (BDNF) has been proposed to be a biomarker of cognitive impairment in these disorders as it plays a critical role in neuroplasticity and proposed to mediate some of the psychotropic effects of medication. However, despite numerous studies investigating the association between circulating BDNF and these disorders, no solid conclusions have been drawn regarding its involvement in cognitive impairment. Objectives: The current systematic review and meta-analysis aims to examine blood BDNF levels and cognitive dysfunction in patients on the schizophrenia-bipolar spectrum as well as to evaluate whether circulating BDNF measurements can act as a biomarker for cognitive dysfunction. Methods: Studies were identified by searching Embase and Medline databases for English language articles published in peer-reviewed journals between 2000 January and 2021 June according to the PRISMA guidelines. A total of 815 articles were identified of which 32 met the inclusion criteria for the systematic review - reporting on comparisons between blood BDNF levels and cognitive functions of schizophrenia or bipolar disorder patients versus healthy controls (no studies involving schizoaffective patients were specifically obtained for the time being). Twenty-four of these studies (19 with schizophrenia and 5 with bipolar disorder patients) were eligible to be included in the meta-analysis. Results: Our findings indicated that circulating BDNF levels were significantly reduced in patients experiencing an acute episode of schizophrenia or bipolar disorder compared to healthy controls. Cognitive function was also found to be significantly worse in patients, however, correlations between BDNF levels and cognitive impairment were not always detected. Interventions, especially pharmacotherapy seemed to improve certain aspects of cognition and increase circulating BDNF levels. Conclusion: Circulating BDNF alone does not seem to be a valid biomarker of cognitive dysfunction in patients with disorders on the schizophrenia-bipolar spectrum, owing to several confounding factors. Changes of the circulating levels of BDNF should be evaluated in a wider context of other stress-, immune-, and inflammatory-related factors.

Original publication




Journal article


Front Psychiatry

Publication Date





BDNF, biomarker, bipolar disorder, cognition, schizoaffective disorder, schizophrenia