Association between the brain-derived neurotrophic factor Val66Met polymorphism and therapeutic response to olanzapine in schizophrenia patients
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Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a major role in neurogenesis and neuroplasticity, and in the modulation of several neurotransmitter systems including the dopaminergic system. There are mixed reports about the association between the BDNF Val66Met polymorphism, schizophrenia, and treatment response to antipsychotic drugs.
The present study evaluated the association of the BDNF Val66Met polymorphism with treatment response to atypical antipsychotic olanzapine in schizophrenia and the possible predictive value of the BDNF Val66Met genotype status in treatment response to antipsychotic medication.
The study included 590 ethnically homogenous Caucasian patients with schizophrenia (diagnosed using the SCID), 40.2 ± 12.0 years old, treated with olanzapine monotherapy (10–20 mg/day), or with other antipsychotics such as risperidone (3–6 mg/day), clozapine (100–500 mg/day), haloperidol (3–115 mg/day), fluphenazine (4–25 mg/day), and quetiapine (50–800 mg/day). Patients were subdivided into responders and non-responders according to a 50 % reduction in the Positive and Negative Syndrome Scale (PANSS) total and subscale scores after 8 weeks of treatment.
The results, corrected for possible effects of gender and age, showed a significant association between the BDNF Val66Met polymorphism and treatment response to olanzapine in patients. The Val/Val genotype was observed more frequently in treatment responders to olanzapine, and this genotype was associated with an improvement in clinical symptoms.
Our results suggest that BDNF Val66Met variants might influence the response to 8 weeks of monotherapy with olanzapine, in a relatively large sample of patients with schizophrenia.
KeywordsAntipsychotics Olanzapine Risperidone Clozapine Haloperidol Fluphenazine Quetiapine BDNF Val66Met polymorphism Schizophrenia Treatment response
- Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS (2004) Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 24:4401–4411PubMedCrossRefGoogle Scholar
- Daniel W (1990) Applied nonparametric statistics. PWS Kent Publishing Company, BostonGoogle Scholar
- Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112:257–269PubMedCrossRefGoogle Scholar
- First MB, Spitzer RL, Williams JBW, Gibbons M (1995) Structured clinical interview for DSM-IV-patient edition (SCID-P). American Psychiatric, Washington DCGoogle Scholar
- Fritz CO, Morris PE, Richler JJ (2012) Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen 141:17Google Scholar
- Gratacos M, Gonzalez JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X (2007) Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case–control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry 61:911–922PubMedCrossRefGoogle Scholar
- Kawashima K, Ikeda M, Kishi T, Kitajima T, Yamanouchi Y, Kinoshita Y, Okochi T, Aleksic B, Tomita M, Okada T, Kunugi H, Inada T, Ozaki N, Iwata N (2009) BDNF is not associated with schizophrenia: data from a Japanese population study and meta-analysis. Schizophr Res 112:72–79PubMedCrossRefGoogle Scholar
- Nikolac M, Nedic G, Sagud M, Zivkovic M, Muck-Seler D, Pivac N (2012) P616: Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and response to antipsychotic drug therapy. E-journal of the British Pharmacological Society Proceedings of the British Pharmacological Society at http://wwwpA2onlineorg/abstracts/Vol10Issue3abst177PpdfGoogle Scholar
- Obermeier M, Schennach-Wolff R, Meyer S, Moller HJ, Riedel M, Krause D, Seemuller F (2011) Is the PANSS used correctly? A systematic review. Bmc Psychiatry 11Google Scholar
- Pivac N, Nikolac M, Nedic G, Mustapic M, Borovecki F, Hajnsek S, Presecki P, Pavlovic M, Mimica N, Muck Seler D (2011) Brain derived neurotrophic factor Val66Met polymorphism and psychotic symptoms in Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 35:356–362PubMedCrossRefGoogle Scholar
- Spatz C (2011) Basic statistics: tales of distributions. Wadsworth, BelmontGoogle Scholar
- Terracciano A, Tanaka T, Sutin AR, Deiana B, Balaci L, Sanna S, Olla N, Maschio A, Uda M, Ferrucci L, Schlessinger D, Costa PT (2010) BDNF Val66Met is associated with introversion and interacts with 5-HTTLPR to influence neuroticism. Neuropsychopharmacology 35:1083–1089PubMedCentralPubMedCrossRefGoogle Scholar
- Zai GC, Zai CC, Chowdhury NI, Tiwari AK, Souza RP, Lieberman JA, Meltzer HY, Potkin SG, Muller DJ, Kennedy JL (2012) The role of brain-derived neurotrophic factor (BDNF) gene variants in antipsychotic response and antipsychotic-induced weight gain. Prog Neuropsychopharmacol Biol Psychiatry 39:96–101PubMedCrossRefGoogle Scholar