BDNF Levels and Genotype are Associated with Antipsychotic-Induced Weight Gain in Patients with Chronic Schizophrenia

Abstract

Recent evidence suggests that centrally released brain-derived neurotrophic factor (BDNF) modulates eating behavior and metabolism that is responsible for body weight fluctuation. BDNF also may play an important role in the therapeutic action of antipsychotic medications. We investigated whether the Val66Met polymorphism of the BDNF gene affected weight gain after long-term antipsychotic treatment in schizophrenia. The polymorphism was genotyped in 196 Chinese patients with schizophrenia on long-term antipsychotic medication. Serum BDNF was measured in all patients and 50 normal controls. Mean body mass index (BMI) change was evaluated retrospectively by means of clinical records. The results showed that there was a significant relationship between the three BDNF Val/ Met genotypes and mean BMI gain, with genotype having a strong effect on BMI gain in male but not female patients. BDNF levels were significantly lower in patients than normal controls, and negatively correlated with BMI gain in female but not male patients. Our results suggest that variation in the BDNF gene may be a risk factor for weight gain in male patients with schizophrenia on long-term antipsychotic treatment, and decreased BDNF levels may be associated with weight gain in females.

Association between brain-derived neurotrophic factor Val66Met and obesity in children and adolescents

“…Since lower serum or plasma BDNF levels are found in obesity (Araya et al, 2008;El-Gharbawy et al, 2006;Gray et al, 2006;Krabbe et al, 2007;Lommatzsch et al, 2005), compared to normal weight subjects, although opposite results also exist (Bus et al, 2011;Iughetti et al, 2011), our data suggest that carriers of one or two Met alleles in our study had decreased amount of the mature BDNF, possibly lower plasma BDNF levels, and therefore they had higher values of BMI and were more frequently obese. This speculation might be confirmed by the fact that weight gain, induced by antipsychotic drugs, is associated with BDNF serum levels in female schizophrenic patients, while carriers of the Met/Met genotype have lower BDNF levels than carriers of the Val allele (Zhang et al, 2008). Our finding of the significant association between BDNF Val66Met genotype and obesity in children and adolescents is supported by GWAS data, which found a significant association between BDNF Val66Met and obesity in children (Zhao et al, 2009) and adults (Croteau-Chonka et al, 2011;Speliotes et al, 2010).…”

Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions

“…15,16 Furthermore, BDNF has been suggested to have an important function in therapeutic action of antipsychotic medications 17 and evidence for association between BDNF genetic variants and antipsychotic-induced weight gain has been reported. 18,19 The hypothesis put forward in this study is that the individual variability in response to risperidone in autism, as well as the occurrence of ADRs, is determined by multiple parameters, among which genetic factors have an important impact. We thus tested the influence of 15 genetic variants in 8 genes (HTR2A, HTR2C, HTR6, DRD2, DRD3, ABCB1, CYP2D6 and BDNF) on risperidone efficacy and the occurrence of ADRs, in 45 autistic patients receiving risperidone up to 1 year.…”

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).…”

“…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.…”