Decreased BDNF in patients with antipsychotic naïve first episode schizophrenia

Abstract

OBJECTIVE-Brain-derived neurotrophic factor (BDNF) is a key factor known to mediate neuronal proliferation, differentiation, survival and response to stress. Decreases in BDNF levels have been reported in schizophrenia, but studies in treatment naïve patients are few. Herein we report on serum BDNF levels in a series of patients with first-episode treatment naïve psychoses in comparison to age matched healthy controls.METHOD-Fasting serum BDNF levels were measured in 41 patients with treatment naive first episode psychosis (24 with schizophrenia, schizoaffective disorder or schizophreniform disorder, and 17 with non-schizophrenia psychotic disorders) and 41 age-matched healthy controls.RESULTS-A three group analyses of covariance (ANCOVA) showed a diagnosis effect (p = .038) in which patients with schizophrenia had lesser serum BDNF levels than patient with nonschizophrenia psychosis, who in turn had lesser BDNF levels than matched healthy controls. Planned two-group ANCOVAs suggested that patients with schizophrenia had lower serum BDNF level than matched controls (p = .016), whereas patients with non-schizophrenia psychosis did not differ from controls. There were no age effects on BDNF, but there was a trend (p = .08) for a gender by group interaction with greater reductions in female patients with schizophrenia. The BDNF levels did not correlate with magnitude of smoking, body mass index, severity of positive and negative symptoms or overall functioning.CONCLUSIONS-Serum BDNF may be reduced at the onset of psychosis but its role in the pathogenesis of schizophrenia remains unclear. Elucidating the role of BDNF in schizophrenia and related psychotic may provide an important therapeutic target. Further studies are also needed to examine if patients with schizophrenia have more pronounced reductions in BDNF than those with affective psychosis.

Psychotic symptoms in young adults exposed to childhood trauma—A 20year follow-up study

“…People with schizophrenia have been shown to have hippocampal volume reduction (Velakoulis et al, 2006), hypothalamic-adrenal-pituitary (HPA) axis dysfunction (Walker et al, 2008), low levels of BDNF (Jindal et al, 2010) and an inverse relationship between cortisol and BDNF in the prefrontal cortex (Issa et al, in press). Taken together, these findings suggest that in a vulnerable individual, trauma may exacerbate changes in brain structure and function leading to increased risk of psychosis.…”

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).…”

“…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).…”

“…Drug-naïve schizophrenic patients without cannabis consumption showed similar results to normal controls and cannabis controls without schizophrenia. In relation to the source of recruitment, 6/16 studies included only inpatients Reis et al, 2008;Rizos et al, 2008;Tan et al, 2005a;Xiu et al, 2009;Zhang et al, 2008), 1/16 included only outpatients (Gama et al, 2007), 3/16 considered both in-patients and out-patients (Carlino et al, 2011;Huang et al, 2006;Ikeda et al, 2008) and 6/16 publications did not provide data (Grillo et al, 2007;Jindal et al, 2010;Jockers-Schrübl et al, 2004;Pirildar et al, 2004;Shimizu et al, 2003;Toyooka et al, 2002). In our research, we found that Japanese subjects were investigated in three studies (Ikeda et al, 2008;Shimizu et al, 2003;Toyooka et al, 2002), Caucasians in another four studies (Carlino et al, 2011;JockersSchrübl et al, 2004;Pirildar et al, 2004, Rizos et al, 2008 and Asians in five studies Huang et al, 2006;Tan et al, 2005a, Zhang et al, 2008.…”

“…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.…”