title: Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications.
abstract: It has been postulated that schizophrenia (SZ) is related to a lower expression of brain-derived neurotrophic factor (BDNF). In the past few years, an increasing number of divergent clinical studies assessing BDNF in serum and plasma have been published. It is now possible to verify the relationship between BDNF levels and severity of symptoms in SZ as well as the effects of antipsychotic drugs on BDNF using meta-analysis. The aims of this study were to verify if peripheral BDNF is decreased in SZ, whether its levels are correlated with positive and negative symptomatology and if BDNF levels change after antipsychotic treatment. This report consists of two distinct meta-analyses of peripheral BDNF in SZ including a total of 41 studies and more than 7000 participants: (1) peripheral BDNF levels in serum and plasma were moderately reduced in SZ compared with controls. Notably, this decrease was accentuated with the disease duration. However, the extent of peripheral BDNF level decrease did not correlate with the severity of positive and negative symptoms. (2) In plasma, but not serum, peripheral BDNF levels are consistently increased after antipsychotic treatment irrespective of the patient's response to medication. In conclusion, there is compelling evidence that there are decreased levels of peripheral BDNF in SZ, in parallel to previously described reduced cerebral BDNF expression. It remains unclear whether these systemic changes are causally related to the development of SZ or if they are merely a pathologic epiphenomenon.
authors.affiliation: Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.|Post-graduate Program in Biological Sciences: Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: B S
authors.initials: BS
authors.lastname: Fernandes
authors.affiliation: Department of Psychiatry, University of Magdeburg, Magdeburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Steiner
authors.affiliation: IMPACT Strategic Research Centre, Deakin University, School of Medicine, Barwon Health, Geelong, VIC, Australia.|Florey Institute for Neuroscience and Mental Health, Department of Psychiatry and Orygen Research Centre, University of Melbourne, Parkville, VIC, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Berk
authors.affiliation: Department of Clinical Psychology, Institute of Psychology, Leiden University, Leiden, The Netherlands.|Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Molendijk
authors.affiliation: University of the Basque Country, Biomedical Research Center in Mental HealthNet (CIBERSAM), Department of Neurosciences, University of the Basque Country, Vitoria, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Pinto
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: C W
authors.initials: CW
authors.lastname: Turck
authors.affiliation: Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.|Post-graduate Program in Biological Sciences: Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Nardin
authors.affiliation: Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.|Post-graduate Program in Biological Sciences: Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: C-A
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor