Decreased levels of serum brain-derived neurotrophic factor in drug-naïve first-episode schizophrenia: relationship to clinical phenotypes

Abstract

Low BDNF levels at the onset of psychosis suggest that it may contribute to the pathogenesis of schizophrenia and perhaps, could be a candidate biological marker for positive symptoms.

State of Art of Serum Brain-Derived Neurotrophic Factor in Schizophrenia

“…Most of the studies (12/16) measuring serum BDNF documented lower concentrations of this neurothropin in patients with schizophrenia (Carlino et al, 2011;Chen et al, 2009;Grillo et al, 2007;Ikeda et al, 2008;Jindal et al, 2010;Jockers-Schrübl et al, 2004;Pirildar et al, 2004;Rizos et al, 2008;Tan et al, 2005a;Toyooka et al, 2002;Xiu et al, 2009;Zhang et al, 2008); however, in other studies, BDNF concentrations were either increased (Gama et al, 2007;Reis et al, 2008); or normal (Huang et al, 2006;Shimizu et al, 2003) (Table 1). Five out of the 16 researches investigated gender effects, demonstrating either significantly lower or higher serum BDNF levels in males suffering from schizophrenia (Gama et al, 2007).…”

“…Six studies reported no diagnostic subtypes of schizophrenia (Ikeda et al, 2008;Gama et al, 2007;Jockers-Schrübl et al, 2004;Pirildar et al, 2004;Reis et al, 2008;Rizos et al, 2008;Toyooka et al, 2002) while in seven studies it was assessed the differences in serum BDNF levels among diagnostic subtypes Grillo et al, 2007;Huang et al, 2006;Shimizu et al, 2003;Tan et al, 2005a;Xiu et al, 2009;Zhang et al, 2008). Different forms of schizophrenia had no association with BDNF serum levels in 5 papers (Grillo et al, 2007, Shimizu et al, 2003Tan et al, 2005a;Xiu et al, 2009;Zhang et al, 2008), while Chen et al (2009) showed significantly higher BDNF levels in paranoid (10.4 ± 4.3 ng/ml) compared to undifferentiated (8.0 ± 3.9 ng/ml) and other combined subtypes (7.5± 4.1 ng/ml). Huang et al (2006) showed that patients with catatonic schizophrenia had lower serum BDNF protein levels than patients with paranoid schizophrenia and residual schizophrenia.…”

“…Most of them (322) did not meet the inclusion criteria, most analyzing val66met BDNF polymorphism, mRNA expression or post-mortem studies. Thus, 17 were finally considered but 16 were actually included in the systematic review (Carlino et al, 2011;Chen et al, 2009;Gama et al, 2007;Grillo et al, 2007;Huang et al, 2006;Ikeda et al, 2008;Jindal et al, 2010;Jockers-Schrübl et al, 2004;Pirildar et al, 2004;Reis et al, 2008;Rizos et al, 2008;Shimizu et al, 2003;Tan et al, 2005a;Toyooka et al, 2002;Zhang et al, 2008). Indeed, as per Authors suggestion, we excluded the study by Zhang et al (2007) (124 patients and 50 controls) since the patients' sample consistently overlapped with that of the study published by Zhang and co-workers in the 2008 (196 patients and 50 controls).…”

“…Fifteen out of the 16 publications considered for the systematic review were used for the meta-analysis (Carlino et al, 2011;Chen et al, 2009;Grillo et al, 2007;Huang et al, 2006;Ikeda et al, 2008;Jindal et al, 2010;Jockers-Schrübl et al, 2004;Pirildar et al, 2004;Reis et al, 2008;Rizos et al, 2008;Shimizu et al, 2003;Tan et al, 2005a;Toyooka et al, 2002;Zhang et al, 2008). The study by Gama et al, (2007) was eliminated, as it was the only one to report serum BDNF in pg/μg of total protein while in all other studies serum BDNF concentration was given in ng or pg/ml serum and therefore, no comparison between the Gama's and the other studies was possible.…”

“…To assess if BDNF can represent a good biomarker in schizophrenia, a growing number of studies compared BDNF serum levels between patients with schizophrenia and healthy control subjects but unfortunately, with controversial results. Indeed, several investigators found a significant decrease in serum BDNF concentrations (Carlino et al, 2011;Chen et al, 2009;Grillo et al, 2007;Ikeda et al, 2008, Jindal et al, 2010Pirildar et al, 2004;Rizos et al, 2008;Shimizu et al, 2002;Tan et al, 2005aTan et al, , 2005bToyooka et al, 2002;Xiu et al, 2009;Zhang et al, 2007Zhang et al, , 2008; while other studies documented normal (Shimizu et al, 2003;JockersSchrubl et al 2004;Huang et al 2006) or even increased circulating BDNF (Gama et al, 2007;Reis et al, 2008). Because of these discrepancies, we decided to perform a systematic review and a meta-analysis of studies measuring serum concentrations of BDNF to elucidate whether or not this neurotrophin is abnormally produced in patients with schizophrenia.…”