Prediction of the response to different classes of antidepressants has been an important matter of concern in the field of psychopharmacology. The purpose of the present study was to investigate whether the G196A polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with the antidepressant effect of milnacipran, a serotonin norepinephrine reuptake inhibitor, and fluvoxamine, a selective serotonin reuptake inhibitor. The subjects of our previous study of milnacipran (n = 80) and fluvoxamine (n = 54) were included in the present study. Severity of depression was assessed with the Montgomery Åsberg depression rating scale (MADRS). Assessments were carried out at baseline and at 1, 2, 4 and 6 weeks of treatment. Polymerase chain reaction was used to determine allelic variants. In all subjects receiving milnacipran or fluvoxamine, the G/A genotype of the BDNF G196A polymorphism was associated with a significantly better therapeutic effect in the MADRS scores during this study. When milnacipran and fluvoxamine-treated subjects were analysed independently, the G/A genotype group showed greater reduction of MADRS scores than other genotype groups, irrespective of which antidepressant was administered. These results suggest that the BDNF G196A polymorphism in part determines the antidepressant effect of both milnacipran and fluvoxamine.
Buchner A., Faul F., Erdfelder E. (1996) G.Power: A priori, post-hoc, and compromise power analyses for the Macintosh (Version 2.1.1) [Computer program]. University of Trier, Trier, Germany
2.
Burke M.J., Preskorn S.H. (1999) Therapeutic drug monitoring of antidepressants: cost implications and relevance to clinical practice. Clin Pharmacokinet37: 147—165
3.
Campbell S., Macqueen G. (2004) The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci29: 417—426
4.
Charlier C., Pinto E., Ansseau M., Plomteux G. (2002) Venlafaxine: the relationship between dose, plasma concentration and clinical response in depressive patients. J Psychopharmacol16: 369—372
Czeh B., Michaelis T., Watanabe T., Frahm J., de Biurrun G., van Kampen M., Bartolomucci A., Fuchs E. (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci U S A98: 12796—12801
7.
Dagher A., Owen A.M., Boecker H., Brooks D.J. (1999) Mapping the network for planning: a correlational PET activation study with the Tower of London task. Brain122 (Pt 10): 1973—1987
8.
Drevets W.C. (1999) Prefrontal cortical-amygdalar metabolism in major depression. Ann N Y Acad Sci877: 614—637
9.
Egan M.F., Kojima M., Callicott J.H., Goldberg T.E., Kolachana B.S., Bertolino A., Zaitsev E., Gold B., Goldman D., Dean M., Lu B., Weinberger D.R. (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell112: 257—269
10.
Foltynie T., Lewis S.G., Goldberg T.E., Blackwell A.D., Kolachana B.S., Weinberger D.R., Robbins T.W., Barker R.A. (2005) The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson's disease. J Neurol252: 833—838
11.
Hawley C.J., Gale T.M., Sivakumaran T. (2002) Defining remission by cut off score on the MADRS: selecting the optimal value. J Affect Disord72: 177—184
12.
Higuchi H., Yoshida K., Takahashi H., Naito S., Kamata M., Ito K., Sato K., Tsukamoto K., Shimizu T., Nakanishi M., Hishikawa Y. (2003) Milnacipran plasma levels and antidepressant response in Japanese major depressive patients. Hum Psychopharmacol18: 255—259
13.
Hong C.J., Huo S.J., Yen F.C., Tung C.L., Pan G.M., Tsai S.J. (2003) Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal behavior . Neuropsychobiology48: 186—189
14.
Kunugi H., Ueki A., Otsuka M., Isse K., Hirasawa H., Kato N., Nabika T., Kobayashi S., Nanko S. (2001) A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease. Mol Psychiatry6: 83—86
15.
Malhotra A.K., Murphy G.M. Jr, Kennedy J.L. (2004) Pharmacogenetics of psychotropic drug response . Am J Psychiatry161: 780—796
16.
Momose Y., Murata M., Kobayashi K., Tachikawa M., Nakabayashi Y., Kanazawa I., Toda T. ( 2002) Association studies of multiple candidate genes for Parkinson's disease using single nucleotide polymorphisms. Ann Neurol51: 133—136
17.
Montgomery S.A., Åsberg M. (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry134: 382—389
18.
Nakata K., Ujike H., Sakai A., Uchida N., Nomura A., Imamura T., Katsu T., Tanaka Y., Hamamura T., Kuroda S. (2003) Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder. Neurosci Lett337: 17—20
19.
Ohkubo T., Shimoyama R., Otani K., Yoshida K., Higuchi H., Shimizu T. (2003) High-performance liquid chromatographic determination of fluvoxamine and fluvoxamino acid in human plasma. AnalSci19: 859—864
20.
Okamoto H., Shino Y., Hashimoto K., Kumakiri C., Shimizu E., Shirasawa H., Iyo M. ( 2003) Dynamic changes in AP-1 transcription factor DNA binding activity in rat brain following administration of antidepressant amitriptyline and brain-derived neurotrophic factor. Neuropharmacology45: 251—259
21.
Perry P.J., Pfohl B.M., Holstad S.G. (1987) The relationship between antidepressant response and tricyclic antidepressant plasma concentrations. A retrospective analysis of the literature using logistic regression analysis. Clin Pharmacokinet13: 381—392
22.
Robbins T.W. (1996) Dissociating executive functions of the prefrontal cortex. Philos Trans R Soc Lond B Biol Sci351: 1463—1470; discussion 1470—1471
23.
Russo-Neustadt A., Beard R.C., Cotman C.W. (1999) Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology21: 679—682
24.
Shirayama Y., Chen A.C., Nakagawa S., Russell D.S., Duman R.S. (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci22: 3251—3261
25.
Smith M.A., Makino S., Kvetnansky R., Post R.M. (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus . J Neurosci15: 1768—1777
26.
Stahl S.M. (2000) Blue genes and the monoamine hypothesis of depression . J Clin Psychiatry61: 77—78
27.
Szekeres G., Juhasz A., Rimanoczy A., Keri S., Janka Z. (2003) The C270T polymorphism of the brain-derived neurotrophic factor gene is associated with schizophrenia. Schizophr Res65: 15—18
28.
Tsai S.J., Cheng C.Y., Yu Y.W., Chen T.J., Hong C.J. (2003) Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology, and antidepressant response. Am J Med Genet B Neuropsychiatr Genet123: 19—22
29.
Yoshida K., Takahashi H., Higuchi H., Kamata M., Ito K., Sato K., Naito S., Shimizu T., Itoh K., Inoue K., Suzuki T., Nemeroff C.B. (2004) Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms. Am J Psychiatry161: 1575—1580
30.
Yoshida K., Ito K., Sato K., Takahashi H., Kamata M., Higuchi H., Shimizu T., Itoh K., Inoue K., Tezuka T., Suzuki T., Ohkubo T., Sugawara K., Otani K. (2002) Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog Neuropsychopharmacol Biol Psychiatry26: 383—386
