The role of brain-derived neurotrophic factor (BDNF) gene variants in antipsychotic response and antipsychotic-induced weight gain.
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.


METHODS
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.


CONCLUSIONS
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.
Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada. gwyneth_zai@camh.net
Gwyneth C M
GC
Zai
Clement C H
CC
Zai
Nabilah I
NI
Chowdhury
Arun K
AK
Tiwari
Renan P
RP
Souza
Jeffrey A
JA
Lieberman
Herbert Y
HY
Meltzer
Steven G
SG
Potkin
Daniel J
DJ
Müller
James L
JL
Kennedy
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002986:Clinical Trials as Topic; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D044465:White People / Q000235:genetics
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor