基因多態性對抗抑郁藥物療效的影響_《華西醫學》

作者：

閔文蛟 ^1,2 , 毛文君 ¹ , 陶立 ³ ,  孫學禮 ²

1 成都市第四人民醫院臨床心理科（成都，610036）;2 四川大學華西醫院心理衛生中心;3四川省安岳縣康復醫院精神科;

關鍵詞：

抑郁癥基因多態性療效

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【摘要】　抑郁癥是臨床常見精神疾病之一，疾病負擔重，而有相當部分患者對抗抑郁藥物治療無效或效果較差。目前研究發現，抑郁癥患者對藥物治療表現出遺傳異質性，一些基因位點，如五羥色胺轉運蛋白基因、五羥色胺2A受體、色氨酸羥化酶基因等，可能與抗抑郁藥物療效相關。本文總結了抗抑郁藥物療效相關基因多態性的研究現狀及進展，對這些基因的深入闡釋有助于在將來研發更為有效的藥物，為抑郁癥患者提供遺傳背景個體化的治療。

引用本文： 閔文蛟,毛文君,陶立,孫學禮. 基因多態性對抗抑郁藥物療效的影響. 華西醫學, 2011, 26(8): 1275-1279. doi: 復制

1.	Brundtland GH. From the World Health Organization. Mental health: new understanding, new hope[J]. JAMA, 2001, 286(19): 2391.
2.	Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in star*D:implications for clinical practice[J]. Am J Psychiatry, 2006, 163(1): 28-40.
3.	O′reilly RL, Bogue L, Singh SM. Pharmacogenetic response to antidepressants in a multicase family with affective disorder[J]. Biol Psychiatry, 1994, 36(7): 467-471.
4.	Serretti A, Benedetti F, Zanardi R, et al. The influence of serotonin transporter promoter polymorphism(SERTPR) and other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatments[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2005, 29(6): 1074-1084.
5.	Kirov G, Rees M, Jones I, et al. Bipolar disorder and the serotonin transporter gene:a family-based association study[J]. Psychol Med, 1999, 29(5): 1249-1254.
6.	Arango V, Underwood MD, Boldrini M, et al. Serotonin 1a receptors,serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims[J]. Neuropsychopharmacology, 2001, 25(6): 892-903.
7.	Mackenzie A, Quinn J. A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo[J]. Proc Natl Acad Sci USA, 1999, 96(26): 15251-15255.
8.	Hranilovic D, Stefulj J, Schwab S, et al. Serotonin transporter promoter and intron 2 polymorphisms:relationship between allelic variants and gene expression[J]. Biol Psychiatry, 2004, 55(11): 1090-1094.
9.	Murphy GM, Hollander SB, Rodrigues HE, et al. Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression[J]. Arch Gen Psychiatry, 2004, 61(11): 1163-1169.
10.	肖紅, 姚輝, 郭蘇婉, 等. 5-羥色胺轉運蛋白基因多態性與抗抑郁藥臨床療效的關系[J]. 中國臨床藥學雜志, 2003, 12(4): 204-207.
11.	Lee MS, Lee HY, Lee HJ, et al. Serotonin transporter promoter gene polymorphism and long-term outcome of antidepressant treatment[J]. Psychiatr Genet, 2004, 14(2): 111-115.
12.	Min W, Li T, Ma X, et al. Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response[J]. Psychopharmacology(Berl), 2009, 205(3): 409-417.
13.	Serretti A, Kato M, De RD, et al. Meta-analysis of serotonin transporter gene promoter polymorphism(5-httlpr)association with selective serotonin reuptake inhibitor efficacy in depressed patients[J]. Mol Psychiatry, 2007, 12(3): 247-257.
14.	Ng CH, Easteal S, Tan S, et al. Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2006, 30(5): 953-957.
15.	Yoshida K, Ito K, Sato K, et al. Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in japanese depressed patients[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2002, 26(2): 383-386.
16.	Kim H, Lim SW, Kim S, et al. Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression[J]. JAMA, 2006, 296(13): 1609-1618.
17.	Ito K, Yoshida K, Sato K, et al. A variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response to fluvoxamine[J]. Psychiatry Res, 2002, 111(2-3): 235-239.
18.	Yates M, Leake A, Candy JM, et al. 5HT2 receptor changes in major depression[J]. Biol Psychiatry, 1990, 27(5): 489-496.
19.	Skrebuhhova T, Allikmets L, Matto V. 5-HT2A receptors mediate the effects of antidepressants in the elevated plus-maze test but have a partial role in the forced swim test[J]. Med Sci Res, 1999, 27(6): 277-280.
20.	Meyer JH, Kapur S, Eisfeld B, et al. The effect of paroxetine on 5-HT(2a) receptors in depression: an[(18)F]setoperone pet imaging study[J]. Am J Psychiatry, 2001, 158(1): 78-85.
21.	Arranz MJ, Munro J, Owen MJ, et al. Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2a receptor gene and response to clozapine[J]. Mol Psychiatry, 1998, 3(1): 61-66.
22.	Choi MJ, Kang RH, Ham BJ, et al. Serotonin receptor 2a gene polymorphism(-1438a/G) and short-term treatment response to citalopram[J]. Neuropsychobiology, 2005, 52(3): 155-162.
23.	Cusin C, Serretti A, Zanardi R, et al. Influence of monoamine oxidase a and serotonin receptor 2a polymorphisms in SSRI antidepressant activity[J]. Int J Neuropsychopharmacol, 2002, 5(1): 27-35.
24.	Benedetti F, Barbini B, Bernasconi A, et al. Serotonin 5-HT2a receptor gene variants influence antidepressant response to repeated total sleep deprivation in bipolar depression[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32(8): 1863-1866.
25.	Sato K, Yoshida K, Takahashi H, et al. Association between-1438G/apromoter polymorphism in the 5-HT(2a)receptor gene and fluvoxamine response in japanese patients with major depressive disorder[J]. Neuropsychobiology, 2002, 46(3): 136-140.
26.	Kato M, Zanardi R, Rossini D, et al. 5-HT2a gene variants influence specific and different aspects of antidepressant response in japanese and italian mood disorder patients[J]. Psychiatry Res, 2009, 167(1-2): 97-105.
27.	Kim SW, Park SY, Hwang O. Up-regulation of tryptophan hydroxylase expression and serotonin synthesis by sertraline[J]. Mol Pharmacol, 2002, 61(4): 778-785.
28.	Pickar D, Rubinow K. Pharmacogenomics of psychiatric disorders[J]. Trends Pharmacol Sci, 2001, 22(2): 75-83.
29.	施梅, 劉薇, 潘尚哈, 等. TPH基因A218C多態性與單相抑郁癥及其癥狀表型的關聯分析[J]. 中國神經精神疾病雜志, 2006, 32(4): 332-335.
30.	Ham BJ, Lee BC, Paik JW, et al. Association between the tryptophan hydroxylase-1 gene a218C polymorphism and citalopram antidepressant response in a korean population[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2007, 31(1): 104-107.
31.	Serretti A, Zanardi R, Rossini D, et al. Influence of tryptophan hydroxylase and serotonin transporter genes on fluvoxamine antidepressant activity[J]. Mol Psychiatry, 2001, 6(5): 586-592.
32.	Yoshida K, Naito S, Takahashi H, et al. Monoamine oxidase: a gene polymorphism, tryptophan hydroxylase gene polymorphism and antidepressant response to fluvoxamine in japanese patients with major depressive disorder[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2002, 26(7-8): 1279-1283.
33.	Ham BJ, Lee MS, Lee HJ, et al. No association between the tryptophan hydroxylase gene polymorphism and major depressive disorders and antidepressant response in a korean population[J]. Psychiatr Genet, 2005, 15(4): 299-301.
34.	Klimek V, Stockmeier C, Overholser J, et al. Reduced levels of norepinephrine transporters in the locus coeruleus in major depression[J]. J Neurosci, 1997, 17(21): 8451-8458.
35.	Jönsson EG, Nöthen MM, Gustavsson JP, et al. Polymorphisms in the dopamine,serotonin,and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers[J]. Psychiatry Res, 1998, 79(1): 1-9.
36.	Kim CH, Kim HS, Cubells JF, et al. A previously undescribed intron and extensive 5’upstream sequence,but not Phox2a-mediated transactivation,are necessary for high level cell type-specific expression of the human norepinephrine transporter gene[J]. J Biol Chem, 1999, 274(10): 6507-6518.
37.	Yoshida K, Takahashi H, Higuchi H, et al. Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms[J]. Am J Psychiatry, 2004, 161(9): 1575-1580.
38.	Baffa A, Hohoff C, Baune BT, et al. Norepinephrine and serotonin transporter genes:impact on treatment response in depression[J]. Neuropsychobiology, 2010, 62(2): 121-131.
39.	Siffert W. G-protein beta3 subunit 825T allele and hypertension[J]. Curr Hypertens Rep, 2003, 5(1): 47-53.
40.	Zill P, Baghai TC, Zwanzger P, et al. Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment[J]. Neuroreport, 2000, 11(9): 1893-1897.
41.	Lee HJ, Cha JH, Ham BJ, et al. Association between a G-protein beta 3 subunit gene polymorphism and the symptomatology and treatment responses of major depressive disorders[J]. Pharmacogenomics J, 2004, 4(1): 29-33.
42.	肖紅, 姚輝, 郭蘇皖, 等. Gβ3基因C825T多態性與抗抑郁藥的臨床療效[J]. 中國臨床藥學雜志, 2003, 12(2): 65-68.
43.	Rosskopf D, Manthey I, Habich C, et al. Identification and characterization of gbeta3s2,a novel splice variant of the G-protein beta3 subunit[J]. Biochem J, 2003, 371(Pt 1): 223-232.
44.	Tadic A, Müller MJ, Rujescu D, et al. The MAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression[J]. Am J Med Genet B Neuropsychiatr Genet, 2007, 144B(3): 325-331.
45.	Lekman M, Laje G, Charney D, et al. The FKBP5-gene in depression and treatment response--an association study in the sequenced treatment alternatives to relieve depression(star*D) cohort[J]. Biol Psychiatry, 2008, 63(12): 1103-1110.
46.	Binder EB, Owens MJ, Liu W, et al. Association of polymorphisms in genes regulating the corticotropin-releasing factor system with antidepressant treatment response[J]. Arch Gen Psychiatry, 2010, 67(4): 369-379.
47.	Burroughs VJ, Maxey RW, Levy RA. Racial and ethnic differences in response to medicines:towards individualized pharmaceutical treatment[J]. J Natl Med Assoc, 2002, 94(10 Suppl): 1-26.
48.	Kraft JB, Peters EJ, Slager SL, et al. Analysis of association between the serotonin transporter and antidepressant response in a large clinical sample[J]. Biol Psychiatry, 2007, 61(6): 734-742.
49.	Mcmahon FJ, Buervenich S, Charney D, et al. Variation in the gene encoding the serotonin 2a receptor is associated with outcome of antidepressant treatment[J]. Am J Hum Genet, 2006, 78(5): 804-814.
50.	Uher R, Perroud N, Ng MY, et al. Genome-wide pharmacogenetics of antidepressant response in the gendep project[J]. Am J Psychiatry, 2010, 167(5): 555-564.
51.	Duman RS, Newton SS. Epigenetic marking and neuronal plasticity[J]. Biol Psychiatry, 2007, 62(1): 1-3.
52.	Nemeroff CB, Vale WW. The neurobiology of depression:inroads to treatment and new drug discovery[J]. J Clin Psychiatry, 2005, 66(Suppl 7): 5-13.

1. 　Brundtland GH. From the World Health Organization. Mental health: new understanding, new hope[J]. JAMA, 2001, 286(19): 2391.
2. 　Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in star*D:implications for clinical practice[J]. Am J Psychiatry, 2006, 163(1): 28-40.
3. 　O′reilly RL, Bogue L, Singh SM. Pharmacogenetic response to antidepressants in a multicase family with affective disorder[J]. Biol Psychiatry, 1994, 36(7): 467-471.
4. 　Serretti A, Benedetti F, Zanardi R, et al. The influence of serotonin transporter promoter polymorphism(SERTPR) and other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatments[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2005, 29(6): 1074-1084.
5. 　Kirov G, Rees M, Jones I, et al. Bipolar disorder and the serotonin transporter gene:a family-based association study[J]. Psychol Med, 1999, 29(5): 1249-1254.
6. 　Arango V, Underwood MD, Boldrini M, et al. Serotonin 1a receptors,serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims[J]. Neuropsychopharmacology, 2001, 25(6): 892-903.
7. 　Mackenzie A, Quinn J. A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo[J]. Proc Natl Acad Sci USA, 1999, 96(26): 15251-15255.
8. 　Hranilovic D, Stefulj J, Schwab S, et al. Serotonin transporter promoter and intron 2 polymorphisms:relationship between allelic variants and gene expression[J]. Biol Psychiatry, 2004, 55(11): 1090-1094.
9. 　Murphy GM, Hollander SB, Rodrigues HE, et al. Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression[J]. Arch Gen Psychiatry, 2004, 61(11): 1163-1169.
10. 　肖紅, 姚輝, 郭蘇婉, 等. 5-羥色胺轉運蛋白基因多態性與抗抑郁藥臨床療效的關系[J]. 中國臨床藥學雜志, 2003, 12(4): 204-207.
11. 　Lee MS, Lee HY, Lee HJ, et al. Serotonin transporter promoter gene polymorphism and long-term outcome of antidepressant treatment[J]. Psychiatr Genet, 2004, 14(2): 111-115.
12. 　Min W, Li T, Ma X, et al. Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response[J]. Psychopharmacology(Berl), 2009, 205(3): 409-417.
13. 　Serretti A, Kato M, De RD, et al. Meta-analysis of serotonin transporter gene promoter polymorphism(5-httlpr)association with selective serotonin reuptake inhibitor efficacy in depressed patients[J]. Mol Psychiatry, 2007, 12(3): 247-257.
14. 　Ng CH, Easteal S, Tan S, et al. Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2006, 30(5): 953-957.
15. 　Yoshida K, Ito K, Sato K, et al. Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in japanese depressed patients[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2002, 26(2): 383-386.
16. 　Kim H, Lim SW, Kim S, et al. Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression[J]. JAMA, 2006, 296(13): 1609-1618.
17. 　Ito K, Yoshida K, Sato K, et al. A variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response to fluvoxamine[J]. Psychiatry Res, 2002, 111(2-3): 235-239.
18. 　Yates M, Leake A, Candy JM, et al. 5HT2 receptor changes in major depression[J]. Biol Psychiatry, 1990, 27(5): 489-496.
19. 　Skrebuhhova T, Allikmets L, Matto V. 5-HT2A receptors mediate the effects of antidepressants in the elevated plus-maze test but have a partial role in the forced swim test[J]. Med Sci Res, 1999, 27(6): 277-280.
20. 　Meyer JH, Kapur S, Eisfeld B, et al. The effect of paroxetine on 5-HT(2a) receptors in depression: an[(18)F]setoperone pet imaging study[J]. Am J Psychiatry, 2001, 158(1): 78-85.
21. 　Arranz MJ, Munro J, Owen MJ, et al. Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2a receptor gene and response to clozapine[J]. Mol Psychiatry, 1998, 3(1): 61-66.
22. 　Choi MJ, Kang RH, Ham BJ, et al. Serotonin receptor 2a gene polymorphism(-1438a/G) and short-term treatment response to citalopram[J]. Neuropsychobiology, 2005, 52(3): 155-162.
23. 　Cusin C, Serretti A, Zanardi R, et al. Influence of monoamine oxidase a and serotonin receptor 2a polymorphisms in SSRI antidepressant activity[J]. Int J Neuropsychopharmacol, 2002, 5(1): 27-35.
24. 　Benedetti F, Barbini B, Bernasconi A, et al. Serotonin 5-HT2a receptor gene variants influence antidepressant response to repeated total sleep deprivation in bipolar depression[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32(8): 1863-1866.
25. 　Sato K, Yoshida K, Takahashi H, et al. Association between-1438G/apromoter polymorphism in the 5-HT(2a)receptor gene and fluvoxamine response in japanese patients with major depressive disorder[J]. Neuropsychobiology, 2002, 46(3): 136-140.
26. 　Kato M, Zanardi R, Rossini D, et al. 5-HT2a gene variants influence specific and different aspects of antidepressant response in japanese and italian mood disorder patients[J]. Psychiatry Res, 2009, 167(1-2): 97-105.
27. 　Kim SW, Park SY, Hwang O. Up-regulation of tryptophan hydroxylase expression and serotonin synthesis by sertraline[J]. Mol Pharmacol, 2002, 61(4): 778-785.
28. 　Pickar D, Rubinow K. Pharmacogenomics of psychiatric disorders[J]. Trends Pharmacol Sci, 2001, 22(2): 75-83.
29. 　施梅, 劉薇, 潘尚哈, 等. TPH基因A218C多態性與單相抑郁癥及其癥狀表型的關聯分析[J]. 中國神經精神疾病雜志, 2006, 32(4): 332-335.
30. 　Ham BJ, Lee BC, Paik JW, et al. Association between the tryptophan hydroxylase-1 gene a218C polymorphism and citalopram antidepressant response in a korean population[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2007, 31(1): 104-107.
31. 　Serretti A, Zanardi R, Rossini D, et al. Influence of tryptophan hydroxylase and serotonin transporter genes on fluvoxamine antidepressant activity[J]. Mol Psychiatry, 2001, 6(5): 586-592.
32. 　Yoshida K, Naito S, Takahashi H, et al. Monoamine oxidase: a gene polymorphism, tryptophan hydroxylase gene polymorphism and antidepressant response to fluvoxamine in japanese patients with major depressive disorder[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2002, 26(7-8): 1279-1283.
33. 　Ham BJ, Lee MS, Lee HJ, et al. No association between the tryptophan hydroxylase gene polymorphism and major depressive disorders and antidepressant response in a korean population[J]. Psychiatr Genet, 2005, 15(4): 299-301.
34. 　Klimek V, Stockmeier C, Overholser J, et al. Reduced levels of norepinephrine transporters in the locus coeruleus in major depression[J]. J Neurosci, 1997, 17(21): 8451-8458.
35. 　Jönsson EG, Nöthen MM, Gustavsson JP, et al. Polymorphisms in the dopamine,serotonin,and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers[J]. Psychiatry Res, 1998, 79(1): 1-9.
36. 　Kim CH, Kim HS, Cubells JF, et al. A previously undescribed intron and extensive 5’upstream sequence,but not Phox2a-mediated transactivation,are necessary for high level cell type-specific expression of the human norepinephrine transporter gene[J]. J Biol Chem, 1999, 274(10): 6507-6518.
37. 　Yoshida K, Takahashi H, Higuchi H, et al. Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms[J]. Am J Psychiatry, 2004, 161(9): 1575-1580.
38. 　Baffa A, Hohoff C, Baune BT, et al. Norepinephrine and serotonin transporter genes:impact on treatment response in depression[J]. Neuropsychobiology, 2010, 62(2): 121-131.
39. 　Siffert W. G-protein beta3 subunit 825T allele and hypertension[J]. Curr Hypertens Rep, 2003, 5(1): 47-53.
40. 　Zill P, Baghai TC, Zwanzger P, et al. Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment[J]. Neuroreport, 2000, 11(9): 1893-1897.
41. 　Lee HJ, Cha JH, Ham BJ, et al. Association between a G-protein beta 3 subunit gene polymorphism and the symptomatology and treatment responses of major depressive disorders[J]. Pharmacogenomics J, 2004, 4(1): 29-33.
42. 　肖紅, 姚輝, 郭蘇皖, 等. Gβ3基因C825T多態性與抗抑郁藥的臨床療效[J]. 中國臨床藥學雜志, 2003, 12(2): 65-68.
43. 　Rosskopf D, Manthey I, Habich C, et al. Identification and characterization of gbeta3s2,a novel splice variant of the G-protein beta3 subunit[J]. Biochem J, 2003, 371(Pt 1): 223-232.
44. 　Tadic A, Müller MJ, Rujescu D, et al. The MAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression[J]. Am J Med Genet B Neuropsychiatr Genet, 2007, 144B(3): 325-331.
45. 　Lekman M, Laje G, Charney D, et al. The FKBP5-gene in depression and treatment response--an association study in the sequenced treatment alternatives to relieve depression(star*D) cohort[J]. Biol Psychiatry, 2008, 63(12): 1103-1110.
46. 　Binder EB, Owens MJ, Liu W, et al. Association of polymorphisms in genes regulating the corticotropin-releasing factor system with antidepressant treatment response[J]. Arch Gen Psychiatry, 2010, 67(4): 369-379.
47. 　Burroughs VJ, Maxey RW, Levy RA. Racial and ethnic differences in response to medicines:towards individualized pharmaceutical treatment[J]. J Natl Med Assoc, 2002, 94(10 Suppl): 1-26.
48. 　Kraft JB, Peters EJ, Slager SL, et al. Analysis of association between the serotonin transporter and antidepressant response in a large clinical sample[J]. Biol Psychiatry, 2007, 61(6): 734-742.
49. 　Mcmahon FJ, Buervenich S, Charney D, et al. Variation in the gene encoding the serotonin 2a receptor is associated with outcome of antidepressant treatment[J]. Am J Hum Genet, 2006, 78(5): 804-814.
50. 　Uher R, Perroud N, Ng MY, et al. Genome-wide pharmacogenetics of antidepressant response in the gendep project[J]. Am J Psychiatry, 2010, 167(5): 555-564.
51. 　Duman RS, Newton SS. Epigenetic marking and neuronal plasticity[J]. Biol Psychiatry, 2007, 62(1): 1-3.
52. 　Nemeroff CB, Vale WW. The neurobiology of depression:inroads to treatment and new drug discovery[J]. J Clin Psychiatry, 2005, 66(Suppl 7): 5-13.

《華西醫學》

基因多態性對抗抑郁藥物療效的影響

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《華西醫學》

基因多態性對抗抑郁藥物療效的影響

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