Skip to main content
SpringerLink
Log in

Polymorphisms of Estrogen Receptors and Risk of Depression

Therapeutic Implications

  • Leading Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Accumulating evidence suggests the involvement of estrogen in depression. Estrogen can modulate neurotransmitter turnover, enhancing the levels of serotonin and noradrenaline (norepinephrine), and it is involved in the regulation of serotonin receptor number and function. Across the female reproductive life, fluctuating estrogen levels and low levels have been associated with depressed mood and there is strong support for a beneficial effect of estrogen-containing hormone treatment in depressed peri-menopausal women. Estrogen exerts its biological effects in large part through intracellular activation of its principal receptors, estrogen receptor α (ESR1) and estrogen receptor β (ESR2). Genetic variation in the estrogen receptors may therefore modify estrogen signalling, thus influencing a womans susceptibility to developing depression. This review provides a synthesis of studies that have examined the association between estrogen receptor polymorphisms and depression-related mood disorders across the lifetime. Studies were identified through a search of the literature from January 1980 until March 2012 using MEDLINE, Web of Knowledge, Cochrane Library and PsycINFO databases.

The studies conducted to date have produced inconsistent findings, which likely relates to the large heterogeneity in terms of the populations, study design and depression measures used. It appears unlikely that the common ESR1 variants rs2234693 and rs9340799 are associated with moderate depressive symptoms in women; however, there is some evidence that indicates a significant association with more severe depressive symptoms, major depressive disorder and anxiety. There are too few studies of ESR2 polymorphisms to draw any definite conclusions; however, preliminary evidence suggests that specific variants may modify the risk of depression associated with the use of hormone treatment in women. Few studies have investigated associations in men, and they have focused almost exclusively on ESR1, but all report non-significant findings. Much work is therefore still needed in this field.

If it is confirmed that specific estrogen receptor polymorphisms are associated with the risk of depression, this could have important preventive and therapeutic implications, with the potential to develop targeted estrogen receptor agonists and antagonists. Furthermore, it is possible that such therapies may be more effective in treating particular people with depression based on their genetic profile, which is an exciting prospect given that many people do not respond to current antidepressant treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I

Similar content being viewed by others

References

  1. Boyd JH, Weissman MM. Epidemiology of affective disorders: a reexamination and future directions. Arch Gen Psychiatry 1981 Sep; 38 (9): 1039–46

    Article  PubMed  CAS  Google Scholar 

  2. Bromberger JT, Kravitz HM, Wei HL, et al. History of depression andwomen’s current health and functioning during midlife. Gen Hosp Psychiatry 2005 May–Jun; 27 (3): 200–8

    Article  PubMed  Google Scholar 

  3. Alonso J, Angermeyer MC, Bernert S, et al. Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology ofMentalDisorders (ESEMeD) project. Acta Psychiatr Scand Suppl 2004; (420): 21-7

  4. Patten SB. Accumulation of major depressive episodes over time in a prospective study indicates that retrospectively assessed lifetime prevalence estimates are too low. BMC Psychiatry 2009; 9: 19

    Article  PubMed  Google Scholar 

  5. Zender R, Olshansky E. Womens mental health: depression and anxiety. Nurs Clin North Am 2009 Sep; 44 (3): 355–64

    Article  PubMed  Google Scholar 

  6. Wilhelm K, Mitchell P, Slade T, et al. Prevalence and correlates of DSM-IV major depression in an Australian national survey. J Affect Disord 2003 Jul; 75 (2): 155–62

    Article  PubMed  Google Scholar 

  7. Gili M, Garcia-Toro M, Vives M, et al. Medical comorbidity in recurrent versus first-episode depressive patients. Acta Psychiatr Scand 2011 Mar; 123 (3): 220–7

    Article  PubMed  CAS  Google Scholar 

  8. Ryan J, Carriere I, Ritchie K, et al. Late-life depression and mortality: influence of gender and antidepressant use. Br J Psychiatry 2008 Jan; 192 (1): 12–8

    Article  PubMed  Google Scholar 

  9. Alexander JL, Dennerstein L, Kotz K, et al. Women, anxiety and mood: a review of nomenclature, comorbidity and epidemiology. Expert Rev Neurother 2007 Nov; 7 (11 Suppl.): S45-58

  10. Sobocki P, Jonsson B, Angst J, et al. Cost of depression in Europe. J Ment Health Policy Econ 2006 Jun; 9 (2): 87–98

    PubMed  Google Scholar 

  11. Lopez-Leon S, Janssens AC, Gonzalez-Zuloeta Ladd AM, et al. Meta-analyses of genetic studies on major depressive disorder. Mol Psychiatry 2008 Aug; 13 (8): 772–85

    Article  PubMed  CAS  Google Scholar 

  12. Ancelin ML, Scali J, Ritchie K. Hormonal therapy and depression: are we overlooking an important therapeutic alternative?. J Psychosom Res 2007 Apr; 62 (4): 473–85

    Article  PubMed  Google Scholar 

  13. Osterlund MK. Underlying mechanisms mediating the antidepressant effects of estrogens. Biochim Biophys Acta 2010 Oct; 1800 (10): 1136–44

    Article  PubMed  CAS  Google Scholar 

  14. Mokrani MC, Duval F, Crocq MA, et al. HPA axis dysfunction in depression: correlation with monoamine system abnormalities. Psychoneuroendocrinology 1997; 22 Suppl. 1: S63–8

    PubMed  CAS  Google Scholar 

  15. Blier P. Crosstalk between the norepinephrine and serotonin systems and its role in the antidepressant response. J Psychiatry Neurosci 2001; 26 Suppl.: S3-10

    Google Scholar 

  16. Meltzer HY. Role of serotonin in depression. Ann N Y Acad Sci 1990; 600: 486–99; discussion 99-500

    Article  PubMed  CAS  Google Scholar 

  17. Hirschfeld RM. History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry 2000; 61 Suppl. 6: 4–6

    PubMed  CAS  Google Scholar 

  18. Andrade TG, Nakamuta JS, Avanzi V, et al. Anxiolytic effect of estradiol in the median raphe nucleus mediated by 5-HT1A receptors. Behav Brain Res 2005 Aug 30; 163 (1): 18–25

    Article  PubMed  CAS  Google Scholar 

  19. Matsuda T, Nakano Y, Kanda T, et al. Gonadal hormones affect the hypothermia induced by serotonin1A (5-HT1A) receptor activation. Life Sci 1991; 48 (17): 1627–32

    Article  PubMed  CAS  Google Scholar 

  20. Summer BE, Fink G. Estrogen increases the density of 5-hydroxytryptamine(2A) receptors in cerebral cortex and nucleus accumbens in the female rat. J Steroid Biochem Mol Biol 1995 Jul; 54 (1–2): 15-20

    Google Scholar 

  21. Halbreich U, Borenstein J, Pearlstein T, et al. The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder. Psychoneuroendocrinology 2003 Aug; 28 Suppl. 3: 1-23

    Google Scholar 

  22. Ryan J, Burger HG, Szoeke C, et al. A prospective study of the association between endogenous hormones and depressive symptoms in postmenopausal women. Menopause 2009 May–Jun; 16 (3): 509–17

    Article  PubMed  Google Scholar 

  23. Soares CN, Zitek B. Reproductive hormone sensitivity and risk for depression across the female life cycle: a continuum of vulnerability?. J Psychiatry Neurosci 2008 Jul; 33 (4): 331–43

    PubMed  Google Scholar 

  24. Ryan J, Carriere I, Scali J, et al. Lifetime hormonal factors may predict late-life depression in women. Int Psychogeriatr 2008 Dec; 20 (6): 1203–18

    Article  PubMed  Google Scholar 

  25. Rapkin AJ. The role of serotonin in premenstrual syndrome. Clin Obstet Gynecol 1992 Sep; 35 (3): 629–36

    Article  PubMed  CAS  Google Scholar 

  26. Cohen LS, Soares CN, Vitonis AF, et al. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch Gen Psychiatry 2006 Apr; 63 (4): 385–90

    Article  PubMed  Google Scholar 

  27. Freeman EW, Sammel MD, Lin H, et al. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry 2006 Apr; 63 (4): 375–82

    Article  PubMed  CAS  Google Scholar 

  28. Bromberger JT, Matthews KA, Schott LL, et al. Depressive symptoms during the menopausal transition: the Study of Women’s Health Across the Nation (SWAN). J Affect Disord 2007 Nov; 103 (1–3): 267-72

    Google Scholar 

  29. Freeman EW. Associations of depression with the transition to menopause. Menopause 2010 Jul; 17 (4): 823–7

    Article  PubMed  Google Scholar 

  30. Zweifel JE, O’Brien WH. A meta-analysis of the effect of hormone replacement therapy upon depressed mood. Psychoneuroendocrinology 1997; 22 (3): 189–212

    Article  PubMed  CAS  Google Scholar 

  31. Cohen LS, Soares CN, Poitras JR, et al. Short-term use of estradiol for depression in perimenopausal and postmenopausal women: a preliminary report. Am J Psychiatry 2003; 160 (8): 1519–22

    Article  PubMed  Google Scholar 

  32. Scali J, Ryan J, Carriere I, et al. A prospective study on hormonal treatment and depression in communitydwelling elderly women (The Three City Study). J Clin Psychiatry 2010 Dec; 71 (12): 1673–9

    Article  PubMed  Google Scholar 

  33. Heldring N, Pike A, Andersson S, et al. Estrogen receptors: how do they signal and what are their targets. Physiol Rev 2007 Jul; 87 (3): 905–31

    Article  PubMed  CAS  Google Scholar 

  34. Osterlund MK, Hurd YL. Estrogen receptors in the human forebrain and the relation to neuropsychiatric disorders. Prog Neurobiol 2001; 64 (3): 251–67

    Article  PubMed  CAS  Google Scholar 

  35. Ostlund H, Keller E, Hurd YL. Estrogen receptor gene expression in relation to neuropsychiatric disorders. Ann N Y Acad Sci 2003 Dec; 1007: 54–63

    Article  PubMed  CAS  Google Scholar 

  36. Kuiper GG, Enmark E, Pelto-Huikko M, et al. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A 1996 Jun 11; 93 (12): 5925–30

    Article  PubMed  CAS  Google Scholar 

  37. Perlman WR, Webster MJ, Kleinman JE, et al. Reduced glucocorticoid and estrogen receptor alpha messenger ribonucleic acid levels in the amygdala of patients with major mental illness. Biol Psychiatry 2004 Dec 1; 56 (11): 844–52

    Article  PubMed  CAS  Google Scholar 

  38. Wissink S, van der Burg B, Katzenellenbogen BS, et al. Synergistic activation of the serotonin-1A receptor by nuclear factor-kappa B and estrogen. Mol Endocrinol 2001 Apr; 15 (4): 543–52

    Article  PubMed  CAS  Google Scholar 

  39. Walf AA, Frye CA. Administration of estrogen receptor beta-specific selective estrogen receptor modulators to the hippocampus decrease anxiety and depressive behavior of ovariectomized rats. Pharmacol Biochem Behav 2007 Feb; 86 (2): 407–14

    Article  PubMed  CAS  Google Scholar 

  40. Rocha BA, Fleischer R, Schaeffer JM, et al. 17 Betaestradiol-induced antidepressant-like effect in the forced swim test is absent in estrogen receptor-beta knockout (BERKO) mice. Psychopharmacology (Berl) (Berl) 2005 May; 179 (3): 637–43

    Article  CAS  Google Scholar 

  41. Nilsson S, Makela S, Treuter E, et al. Mechanisms of estrogen action. Physiol Rev 2001 Oct; 81 (4): 1535–65

    PubMed  CAS  Google Scholar 

  42. McEwen BS, Alves SE, Bulloch K, et al. Ovarian steroids and the brain: implications for cognition and aging. Neurology 1997 May; 48 (5 Suppl. 7): S8-15

  43. Katzenellenbogen BS. Dynamics of steroid hormone receptor action. Annu Rev Physiol 1980; 42: 17–35

    Article  PubMed  CAS  Google Scholar 

  44. BrannDW, Dhandapani K, Wakade C, et al. Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids 2007 May; 72 (5): 381–405

    Article  PubMed  CAS  Google Scholar 

  45. Matthews J, Wihlen B, Tujague M, et al. Estrogen receptor (ER) beta modulates ERalpha-mediated transcriptional activation by altering the recruitment of c-Fos and c-Jun to estrogen-responsive promoters. Mol Endocrinol 2006 Mar; 20 (3): 534–43

    Article  PubMed  CAS  Google Scholar 

  46. Pettersson K, Delaunay F, Gustafsson JA. Estrogen receptor beta acts as a dominant regulator of estrogen signaling. Oncogene 2000 Oct 12; 19 (43): 4970–8

    Article  PubMed  CAS  Google Scholar 

  47. Liu MM, Albanese C, Anderson CM, et al. Opposing action of estrogen receptors alpha and beta on cyclin D1 gene expression. J Biol Chem 2002 Jul 5; 277 (27): 24353–60

    Article  PubMed  CAS  Google Scholar 

  48. Pace P, Taylor J, Suntharalingam S, et al. Human estrogen receptor beta binds DNA in a manner similar to and dimerizes with estrogen receptor alpha. J Biol Chem 1997 Oct 10; 272 (41): 25832–8

    Article  PubMed  CAS  Google Scholar 

  49. Almeida S, Hutz MH. Genetic variation of estrogen metabolism and the risks of cardiovascular disease. Curr Opin Investig Drugs 2007 Oct; 8 (10): 814–20

    PubMed  CAS  Google Scholar 

  50. Ryan J, Canonico M, Carcaillon L, et al. Hormone treatment, estrogen receptor polymorphisms and mortality: a prospective cohort study. PLoS ONE 2012; 7 (3): e34112

    Google Scholar 

  51. Silvestri S, Thomsen AB, Gozzini A, et al. Estrogen receptor alpha and beta polymorphisms: is there an association with bone mineral density, plasma lipids, and response to postmenopausal hormone therapy?. Menopause 2006 May–Jun; 13 (3): 451–61

    Article  PubMed  Google Scholar 

  52. Herrington DM, Howard TD, Brosnihan KB, et al. Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-reactive protein. Circulation 2002 Apr 23; 105 (16): 1879–82

    Article  PubMed  CAS  Google Scholar 

  53. Maruyama H, Toji H, Harrington CR, et al. Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease. Arch Neurol 2000; 57 (2): 236–40

    Article  PubMed  CAS  Google Scholar 

  54. Greendale GA, Chu J, Ferrell R, et al. The association of bone mineral density with estrogen receptor gene polymorphisms. Am J Med 2006 Sep; 119 (9 Suppl. 1): S79-86

    Google Scholar 

  55. Kobayashi N, Fujino T, Shirogane T, et al. Estrogen receptor alpha polymorphism as a genetic marker for bone loss, vertebral fractures and susceptibility to estrogen. Maturitas 2002 Mar 25; 41 (3): 193–201

    Article  PubMed  CAS  Google Scholar 

  56. Malacara JM, Perez-Luque EL, Martinez-Garza S, et al. The relationship of estrogen receptor-alpha polymorphism with symptoms and other characteristics in postmenopausal women. Maturitas 2004 Oct 15; 49 (2): 163–9

    Article  PubMed  CAS  Google Scholar 

  57. Weel AE, Uitterlinden AG, Westendorp IC, et al. Estrogen receptor polymorphism predicts the onset of natural and surgical menopause. J Clin Endocrinol Metab 1999 Sep; 84 (9): 3146–50

    Article  PubMed  CAS  Google Scholar 

  58. Kjaergaard AD, Ellervik C, Tybjaerg-Hansen A, et al. Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis. Circulation 2007 Feb 20; 115 (7): 861–71

    Article  PubMed  CAS  Google Scholar 

  59. Alevizaki M, Saltiki K, Cimponeriu A, et al. Severity of cardiovascular disease in postmenopausal women: associations with common estrogen receptor alpha polymorphic variants. Eur J Endocrinol 2007 Apr; 156 (4): 489–96

    Article  PubMed  CAS  Google Scholar 

  60. Shearman AM, Cooper JA, Kotwinski PJ, et al. Estrogen receptor alpha gene variation and the risk of stroke. Stroke 2005 Oct; 36 (10): 2281–2

    Article  PubMed  CAS  Google Scholar 

  61. Boada M, Antunez C, Lopez-Arrieta J, et al. Estrogen receptor alpha gene variants are associated with Alzheimer’s disease. Neurobiol Aging 2012 Jan; 33 (1): 198.e15–24

    Google Scholar 

  62. Becherini L, Gennari L, Masi L, et al. Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor alpha gene and their relationship to bone mass variation in postmenopausal Italian women. Hum Mol Genet 2000 Aug 12; 9 (13): 2043–50

    Article  PubMed  CAS  Google Scholar 

  63. del Senno L, Aguiari GL, Piva R. Dinucleotide repeat polymorphism in the human estrogen receptor (ESR) gene. Hum Mol Genet 1992 Aug; 1 (5): 354

    Google Scholar 

  64. Yim CH, Choi JT, Choi HA, et al. Association of estrogen receptor alpha gene microsatellite polymorphism with annual changes in bone mineral density in Korean women with hormone replacement therapy. J Bone Miner Metab 2005; 23 (5): 395–400

    Article  PubMed  CAS  Google Scholar 

  65. Kunnas TA, Laippala P, Penttila A, et al. Association of polymorphism of human alpha oestrogen receptor gene with coronary artery disease in men: a necropsy study. BMJ 2000 Jul 29; 321 (7256): 273–4

    Article  PubMed  CAS  Google Scholar 

  66. Domingues-Montanari S, Subirana I, Tomas M, et al. Association between ESR2 genetic variants and risk of myocardial infarction. Clin Chem 2008 Jul; 54 (7): 1183–9

    Article  PubMed  CAS  Google Scholar 

  67. Giedraitis V, Kilander L, Degerman-Gunnarsson M, et al. Genetic analysis of Alzheimer’s disease in the Uppsala Longitudinal Study of Adult Men. Dement Geriatr Cogn Disord 2009; 27 (1): 59–68

    Article  PubMed  Google Scholar 

  68. Gold B, Kalush F, Bergeron J, et al. Estrogen receptor genotypes and haplotypes associated with breast cancer risk. Cancer Res 2004 Dec 15; 64 (24): 8891–900

    Article  PubMed  CAS  Google Scholar 

  69. He LN, Xiong DH, Liu YJ, et al. Association study of the oestrogen signalling pathway genes in relation to age at natural menopause. J Genet 2007 Dec; 86 (3): 269–76

    Article  PubMed  CAS  Google Scholar 

  70. Rexrode KM, Ridker PM, Hegener HH, et al. Polymorphisms and haplotypes of the estrogen receptor-beta gene (ESR2) and cardiovascular disease in men and women. Clin Chem 2007 Oct; 53 (10): 1749–56

    Article  PubMed  CAS  Google Scholar 

  71. Sowers MR, Jannausch ML, McConnell DS, et al. Endogenous estradiol and its association with estrogen receptor gene polymorphisms. Am J Med 2006 Sep; 119 (9 Suppl. 1): S16-22

    Google Scholar 

  72. Takeo C, Negishi E, Nakajima A, et al. Association of cytosine- adenine repeat polymorphism of the estrogen receptor-beta gene with menopausal symptoms. Gend Med 2005 Jun; 2 (2): 96–105

    Article  PubMed  Google Scholar 

  73. Yaffe K, Lindquist K, Sen S, et al. Estrogen receptor genotype and risk of cognitive impairment in elders: findings from the Health ABC study. Neurobiol Aging 2009 Apr; 30 (4): 607–14

    Article  PubMed  CAS  Google Scholar 

  74. Prichard Z, Jorm AF, Prior M, et al. Association of polymorphisms of the estrogen receptor gene with anxietyrelated traits in children and adolescents: a longitudinal study. Am J Med Genet 2002 Mar 8; 114 (2): 169–76

    Article  PubMed  Google Scholar 

  75. Comings DE, Muhleman D, Johnson P, et al. Potential role of the estrogen receptor gene (ESR1) in anxiety. Mol Psychiatry 1999 Jul; 4 (4): 374–7

    Article  PubMed  CAS  Google Scholar 

  76. Kravitz HM, Janssen I, Lotrich FE, et al. Sex steroid hormone gene polymorphisms and depressive symptoms in women at midlife. Am J Med 2006 Sep; 119 (9 Suppl. 1): S87–93

    Article  PubMed  CAS  Google Scholar 

  77. Zhou B, Sun X, Zhang M, et al. The symptomatology of climacteric syndrome: whether associated with the physical factors or psychological disorder in perimenopausal/postmenopausal patients with anxiety-depression disorder. Arch Gynecol Obstet 2012 May; 285 (5): 1345–52

    Article  PubMed  Google Scholar 

  78. Tiemeier H, Schuit SC, den Heijer T, et al. Estrogen receptor alpha gene polymorphisms and anxiety disorder in an elderly population. Mol Psychiatry 2005 Sep; 10 (9): 806–7

    Article  PubMed  CAS  Google Scholar 

  79. Yalamanchili V, Gallagher JC. Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms. Menopause 2012 Jun; 19 (6): 697–703

    Article  PubMed  Google Scholar 

  80. Mill J, Kiss E, Baji I, et al. Association study of the estrogen receptor alpha gene (ESR1) and childhood-onset mood disorders. Am J Med Genet B Neuropsychiatr Genet 2008 Oct 5; 147B (7): 1323-6

  81. Geng YG, Su QR, Su LY, et al. Comparison of the polymorphisms of androgen receptor gene and estrogen alpha and beta gene between adolescent females with first-onset major depressive disorder and controls. Int J Neurosci 2007 Apr; 117 (4): 539–47

    Article  PubMed  CAS  Google Scholar 

  82. Huo L, Straub RE, Roca C, et al. Risk for premenstrual dysphoric disorder is associated with genetic variation in ESR1, the estrogen receptor alpha gene. Biol Psychiatry 2007 Oct 15; 62 (8): 925–33

    Article  PubMed  CAS  Google Scholar 

  83. Kishi T, Ikeda M, Kitajima T, et al. Association analysis of functional polymorphism in estrogen receptor alpha gene with schizophrenia and mood disorders in the Japanese population. Psychiatr Genet 2009 Aug; 19 (4): 217–8

    Article  PubMed  Google Scholar 

  84. Tsai SJ, Wang YC, Hong CJ, et al. Association study of oestrogen receptor alpha gene polymorphism and suicidal behaviours in major depressive disorder. Psychiatr Genet 2003 Mar; 13 (1): 19–22

    Article  PubMed  Google Scholar 

  85. Kim JJ, Pae CU, Kim MR, et al. Association between estrogen receptor gene polymorphisms and depression in post-menopausal women: a preliminary study. Psychiatry Investig 2010 Sep; 7 (3): 224–7

    Article  PubMed  Google Scholar 

  86. Ryan J, Scali J, Carriere I, et al. Oestrogen receptor polymorphisms and late-life depression. Br J Psychiatry 2011 Aug; 199: 126–31

    Article  PubMed  Google Scholar 

  87. Ryan J, Scali J, Carriere I, et al. Estrogen receptor alpha gene variants and major depressive episodes. J Affect Disord 2012 Feb; 136 (3): 1222–6

    Article  PubMed  CAS  Google Scholar 

  88. Jones I, Middle F, McCandless F, et al. Molecular genetic studies of bipolar disorder and puerperal psychosis at two polymorphisms in the estrogen receptor alpha gene (ESR 1). Am J Med Genet 2000 Dec 4; 96 (6): 850–3

    Article  PubMed  CAS  Google Scholar 

  89. Feng J, Yan J, Michaud S, et al. Scanning of estrogen receptor alpha (ERalpha) and thyroid hormone receptor alpha (TRalpha) genes in patients with psychiatric diseases: four missense mutations identified in ERalpha gene. Am J Med Genet 2001 May 8; 105 (4): 369–74

    Article  PubMed  CAS  Google Scholar 

  90. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition. Washington, DC: American Psychiatric Association, 1994

  91. Ryan J, Scali J, Carriere I, et al. Estrogen receptor gene variants are associated with anxiety disorders in older women. Psychoneuroendocrinology 2011 Nov; 36 (10): 1582–6

    Article  PubMed  CAS  Google Scholar 

  92. Alonso P, Gratacos M, Segalas C, et al. Variants in estrogen receptor alpha gene are associated with phenotypical expression of obsessive-compulsive disorder. Psychoneuroendocrinology 2011 May; 36 (4): 473–83

    Article  PubMed  CAS  Google Scholar 

  93. Lambert JC, Harris JM, Mann D, et al. Are the estrogen receptors involved in Alzheimer’s disease?. Neurosci Lett 2001; 306 (3): 193–7

    Article  PubMed  CAS  Google Scholar 

  94. Gillies GE, McArthur S. Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines. Pharmacol Rev 2010 Jun; 62 (2): 155–98

    Article  PubMed  CAS  Google Scholar 

  95. Shen LX, Basilion JP, Stanton VP, et al. Single-nucleotide polymorphisms can cause different structural folds of mRNA. Proc Natl Acad Sci U S A 1999 Jul 6; 96 (14): 7871–6

    Article  PubMed  CAS  Google Scholar 

  96. Duan J, Wainwright MS, Comeron JM, et al. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet 2003 Feb 1; 12 (3): 205–16

    Article  PubMed  CAS  Google Scholar 

  97. Aronow B, Lattier D, Silbiger R, et al. Evidence for a complex regulatory array in the first intron of the human adenosine deaminase gene. Genes Dev 1989 Sep; 3 (9): 1384–400

    Article  PubMed  CAS  Google Scholar 

  98. Schuit SC, de Jong FH, Stolk L, et al. Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women. Eur J Endocrinol 2005 Aug; 153 (2): 327–34

    Article  PubMed  CAS  Google Scholar 

  99. Yaffe K, Lui LY, Grady D, et al. Estrogen receptor 1 polymorphisms and risk of cognitive impairment in older women. Biol Psychiatry 2002; 51 (8): 677–82

    Article  PubMed  CAS  Google Scholar 

  100. Gennari L, De Paola V, Merlotti D, et al. Steroid hormone receptor gene polymorphisms and osteoporosis: a pharmacogenomic review. Expert Opin Pharmacother 2007 Apr; 8 (5): 537–53

    Article  PubMed  CAS  Google Scholar 

  101. Sundermann EE, Maki PM, Bishop JR. A review of estrogen receptor alpha gene (ESR1) polymorphisms, mood, and cognition. Menopause 2010 Jul; 17 (4): 874–86

    Article  PubMed  Google Scholar 

  102. Perlman WR, Tomaskovic-Crook E, Montague DM, et al. Alteration in estrogen receptor alpha mRNA levels in frontal cortex and hippocampus of patients with major mental illness. Biol Psychiatry 2005 Nov 15; 58 (10): 812–24

    Article  PubMed  CAS  Google Scholar 

  103. Gennari L, Merlotti D, De Paola V, et al. Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol 2005 Feb 15; 161 (4): 307–20

    Article  PubMed  CAS  Google Scholar 

  104. Nilsson S, Gustafsson JA. Estrogen receptors: therapies targeted to receptor subtypes. Clin Pharmacol Ther 2011 Jan; 89 (1): 44–55

    Article  PubMed  CAS  Google Scholar 

  105. Zhao L, O’Neill K, Diaz Brinton R. Selective estrogen receptor modulators (SERMs) for the brain: current status and remaining challenges for developing NeuroSERMs. Brain Res Brain Res Rev 2005 Nov; 49 (3): 472–93

    Article  PubMed  CAS  Google Scholar 

  106. Ongphiphadhanakul B, Chanprasertyothin S, Payatikul P, et al. Oestrogen-receptor-alpha gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women. Clin Endocrinol (Oxf) 2000 May; 52 (5): 581–5

    Article  CAS  Google Scholar 

  107. Abbas S, Brauch H, Chang-Claude J, et al. Polymorphisms in genes of the steroid receptor superfamily modify postmenopausal breast cancer risk associated with menopausal hormone therapy. Int J Cancer 2010 Jun 15; 126 (12): 2935–46

    CAS  Google Scholar 

  108. Herrington DM, Howard TD, Hawkins GA, et al. Estrogen-receptor polymorphisms and effects of estrogen replacement on high-density lipoprotein cholesterol in women with coronary disease. N Engl J Med 2002; 346 (13): 967–74

    Article  PubMed  CAS  Google Scholar 

  109. van Duijnhoven FJ, Peeters PH, Warren RM, et al. Influence of estrogen receptor alpha and progesterone receptor polymorphisms on the effects of hormone therapy on mammographic density. Cancer Epidemiol Biomarkers Prev 2006 Mar; 15 (3): 462–7

    Article  PubMed  Google Scholar 

  110. Nemeroff CB. Prevalence and management of treatmentresistant depression. J Clin Psychiatry 2007; 68 Suppl. 8: 17–25

    PubMed  CAS  Google Scholar 

  111. Cassano P, Soares CN, Cusin C, et al. Antidepressant response and well-being in pre-, peri- and postmenopausal women with major depressive disorder treated with fluoxetine. Psychother Psychosom 2005; 74 (6): 362–5

    Article  PubMed  Google Scholar 

  112. Kornstein SG, Schatzberg AF, Thase ME, et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry 2000; 157 (9): 1445–52

    Article  PubMed  CAS  Google Scholar 

  113. Archer JS. NAMS/Solvay Resident Essay Award. Relationship between estrogen, serotonin, and depression. Menopause 1999; 6 (1): 71–8

    CAS  Google Scholar 

  114. Schmidt PJ, Nieman L, Danaceau MA, et al. Estrogen replacement in perimenopause-related depression: a preliminary report. Am J Obstet Gynecol 2000; 183 (2): 414–20

    Article  PubMed  CAS  Google Scholar 

  115. Soares CN, Almeida OP, Joffe H, et al. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebocontrolled trial. Arch Gen Psychiatry 2001; 58 (6): 529–34

    Article  PubMed  CAS  Google Scholar 

  116. Soares CN, Arsenio H, Joffe H, et al. Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic peri- and postmenopausal women: impact on depression, vasomotor symptoms, sleep, and quality of life. Menopause 2006 Sep–Oct; 13 (5): 780–6

    Article  PubMed  Google Scholar 

  117. Soares CN, Poitras JR, Prouty J, et al. Efficacy of citalopram as a monotherapy or as an adjunctive treatment to estrogen therapy for perimenopausal and postmenopausal women with depression and vasomotor symptoms. J Clin Psychiatry 2003 Apr; 64 (4): 473–9

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. Joanne Ryan is the holder of an NHMRC Training (Postdoctoral) Fellowship (Overseas Public Health, APP1012735). All authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Inserm U1061, Hôpital La Colombière, 39 avenue Charles Flahault, BP 34493, 34093, Montpellier Cedex 5, France

    Joanne Ryan & Marie-Laure Ancelin

  2. University Montpellier 1, U1061, Montpellier, France

    Joanne Ryan & Marie-Laure Ancelin

  3. Murdoch Children’s Research Institute (MCRI), Royal Children’s Hospital, Parkville, VIC, Australia

    Joanne Ryan

Authors
  1. Joanne Ryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie-Laure Ancelin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joanne Ryan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ryan, J., Ancelin, ML. Polymorphisms of Estrogen Receptors and Risk of Depression. Drugs 72, 1725–1738 (2012). https://doi.org/10.2165/11635960-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11635960-000000000-00000

Keywords

Search

Navigation