TY - JOUR
T1 - The role of brain-derived neurotrophic factor (BDNF) gene variants in antipsychotic response and antipsychotic-induced weight gain
AU - Zai, Gwyneth C.M.
AU - Zai, Clement C.H.
AU - Chowdhury, Nabilah I.
AU - Tiwari, Arun K.
AU - Souza, Renan P.
AU - Lieberman, Jeffrey A.
AU - Meltzer, Herbert Y.
AU - Potkin, Steven G.
AU - Müller, Daniel J.
AU - Kennedy, James L.
N1 - Funding Information:
DJM/CCZ/GCZ/NIC/RPS/AKT reported no competing interests. HYM has received grants or is a consultant to: Abbott Labs, ACADIA, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Astra Zeneca, GlaxoSmithKline, Memory, Cephalon, Minster, Aryx, and BiolineRx. HYM is a shareholder of ACADIA. JAL reports having received research funding or consulting or educational fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Labs, GlaxoSmithKline, Janssen, Novartis, Pfizer, and Solvay. SGP: consultancy/board of advisors/honoraria: American Psychiatric Association, Astra Zeneca, Bioline, Bristol-Myers Squibb, Cortex, Dainippon-Sumitomo, Janssen Pharmaceutica, Novartis, Organon, Otsuka, Pfizer, Roche, Schering Plough,Vanda; research grants: Astra Zeneca, Bioline, Bristol-Myers Squibb, Dainippon Sumitomo, Elan, Forest Laboratories, Fujisawa, Janssen Pharmaceutica, Merck, Novartis, Ono, Organon, Otsuka, Pfizer, Solvay Pharmaceuticals, Roche, NIH, Harvard Massachusetts General Hospital, Brigham and Women's Hospital, Vanda, Wyeth; speakers' bureau: Astra Zeneca, Bristol-Meyers Squibb, ISCTM, Novartis, Pfizer. JLK has been a consultant to GSK, Sanofi-Aventis, Dainippon-Sumitomo.
Funding Information:
This study is supported by the Canadian Institutes of Health Research, Ontario Mental Health Foundation, American Foundation for Suicide Prevention, and Eli Lilly. The funding sources had no further role in study designs; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Funding Information:
CIHR operating grant to JLK ( MOP 115097 ) and DJM (Genetics of antipsychotics induced metabolic syndrome, MOP 89853 ); NARSAD Young Investigator Award to DJM and AKT, CIHR Michael Smith New Investigator Salary Prize for Research in Schizophrenia to DJM, OMHF New Investigator Fellowship to DJM; fellowship funding from American Foundation for Suicide Prevention and Eli Lilly to CCZ. We are greatly indebted to the patients who agreed to participate.
PY - 2012/10/1
Y1 - 2012/10/1
N2 - Background: Brain-derived neurotrophic factor (BDNF) has extensive effects on the nervous system including cell survival, differentiation, neuronal growth and maintenance, as well as cell death. Moreover, it promotes synaptic plasticity and interacts with dopaminergic and serotonergic neurons, suggesting an important role on the alteration of brain function with antipsychotic medications and induced weight gain in schizophrenia patients. The differential effects of BDNF gene variants could lead to changes in brain circuitry that would in turn cause variable response to antipsychotic medication. Therefore, we hypothesized that genetic variation in this candidate gene helps in explaining the inter-individual variation observed in antipsychotic drug treatment with respect to response and induced weight gain. Method: We examined four single-nucleotide polymorphisms across the BDNF gene, including Val66Met (rs6265). Prospective BPRS change scores and weight change after six weeks were obtained from a total of 257 schizophrenia patients of European ancestry. Results: The markers rs11030104 and Val66Met were associated with antipsychotic response (P= 0.04; 0.007, respectively). On the other hand, marker rs1519480 was associated with weight gain (P= 0.04). Moreover, a two-marker haplotype across rs6265 and rs1519480 was associated with weight change (P= 0.001). Results with Val66Met in response, and results with rs6265-rs1519480 haplotypes remained significant at the modified Bonferroni corrected alpha of 0.017. Conclusion: BDNF genetic variants might play an important role in predicting antipsychotic response and antipsychotic-induced weight gain. However, replication in larger and independent samples is required.
AB - Background: Brain-derived neurotrophic factor (BDNF) has extensive effects on the nervous system including cell survival, differentiation, neuronal growth and maintenance, as well as cell death. Moreover, it promotes synaptic plasticity and interacts with dopaminergic and serotonergic neurons, suggesting an important role on the alteration of brain function with antipsychotic medications and induced weight gain in schizophrenia patients. The differential effects of BDNF gene variants could lead to changes in brain circuitry that would in turn cause variable response to antipsychotic medication. Therefore, we hypothesized that genetic variation in this candidate gene helps in explaining the inter-individual variation observed in antipsychotic drug treatment with respect to response and induced weight gain. Method: We examined four single-nucleotide polymorphisms across the BDNF gene, including Val66Met (rs6265). Prospective BPRS change scores and weight change after six weeks were obtained from a total of 257 schizophrenia patients of European ancestry. Results: The markers rs11030104 and Val66Met were associated with antipsychotic response (P= 0.04; 0.007, respectively). On the other hand, marker rs1519480 was associated with weight gain (P= 0.04). Moreover, a two-marker haplotype across rs6265 and rs1519480 was associated with weight change (P= 0.001). Results with Val66Met in response, and results with rs6265-rs1519480 haplotypes remained significant at the modified Bonferroni corrected alpha of 0.017. Conclusion: BDNF genetic variants might play an important role in predicting antipsychotic response and antipsychotic-induced weight gain. However, replication in larger and independent samples is required.
KW - Antipsychotic response
KW - Antipsychotic-induced weight gain
KW - Brain-derived neurotrophic factor (BDNF)
KW - Pharmacogenetics
KW - Schizophrenia
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U2 - 10.1016/j.pnpbp.2012.05.014
DO - 10.1016/j.pnpbp.2012.05.014
M3 - Article
C2 - 22642961
AN - SCOPUS:84864510413
SN - 0278-5846
VL - 39
SP - 96
EP - 101
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
IS - 1
ER -