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The Role of Central Serotonergic Dysfunction in the Aetiology of Premenstrual Dysphoric Disorder

Therapeutic Implications

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Abstract

Premenstrual dysphoric disorder (PMDD), as defined in DSM-IV, is a mood disorder. One of the leading theories for the pathogenesis of mood disorders is dysfunction of the serotonergic system. An increasing database suggests that serotonergic dysfunction also characterises PMDD. Evidence that treatments which enhance serotonergic function are beneficial in reducing the symptoms of PMDD support this hypothesis. Indeed, most of the evidence from baseline studies suggests predominantly a serotonergic rather than a noradrenergic or dopaminergic dysfunction. Challenge studies further support this hypothesis. These findings of neurotransmitter dysfunction are more consistent than those of other neuroendocrine abnormalities for example. Based on treatment studies, a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, fluoxetine, has been approved for use in PMDD by the US Food and Drug Administration.

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References

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

    Google Scholar 

  2. Meltzer HY. Role of serotonin in depression. Ann NY Acad Sci 1990; 600: 486–95

    Article  PubMed  CAS  Google Scholar 

  3. Gold JH, Endicott J, Parry BL, et al. Late luteal phase dysphoric disorder. In: Widiger TA, Frances AJ, Pincus HA, et al., editors. DSM-IV sourcebook. Vol 2. American Psychiatric Association: Washington D.C., 1996; 14: 317–94

    Google Scholar 

  4. Lepage P, Steiner M. Gender and serotonergic dysregulation: implications for late luteal phase dysphoric disorder. In: Serotonin-related psychiatric syndromes: clinical and therapeutic links: proceedings of an international meeting held under the auspices of the Italian Society of Neuroscience and sponsored by Eli Lilly Italia SpA. Venice; 1990 Mar 29–31. International Congress and Symposium Series. London: Royal Society of Medicine Services 1991; 165: 131–43

    Google Scholar 

  5. Rubinow DR, Schmidt PJ, Roca CA. Estrogen-serotonin interactions: implications for affective regulation. Biol Psychiatry 1998; 44: 839–50

    Article  PubMed  CAS  Google Scholar 

  6. Bethea CL, Pecins-Thompson M, Schutzer WE, et al. Ovarian steroids and serotonin neural function. Mol Neurobiol 1998; 18(2): 87–123

    Article  PubMed  CAS  Google Scholar 

  7. Dunn EJ, Steiner M. The functional neurochemistry of mood disorders in women. In: Steiner M, editor. Mood disorders in women. London: Dunitz, 2000: 71–82

    Google Scholar 

  8. Biegon A, Fischette CT, Raibow TC, et al. Serotonergic receptor modulation by estrogen in discrete brain nuclei. Neuroendocrinology 1982; 35: 287–91

    Article  PubMed  CAS  Google Scholar 

  9. Futo J, Shay J, Block S, et al. Estrogen and progesterone withdrawal increases cerebral vasoreactivity to serotonin in rabbit basilar artery. Life Sci 1992; 50: 1165–72

    Article  PubMed  CAS  Google Scholar 

  10. Sumner BEH, Fink G. Effects of acute estradiol on 5-OH tryptamine and dopamine receptor subtype mRNA expression in female rat brain. Mol Cell Neurosci 1993; 4: 83–92

    Article  PubMed  CAS  Google Scholar 

  11. Fink G, Sumner BEH, Rosie R, et al. Estrogen control of central neurotransmission: effect on mood, mental state and memory. Cell Mol Neurobiol 1996; 16: 325–44

    Article  PubMed  CAS  Google Scholar 

  12. Ashby CR, Carr LA, Cook CL, et al. Alteration of platelet serotonergic mechanisms and monoamine oxidase activity in premenstraal syndrome. Biol Psychology 1988; 24: 225–33

    Article  CAS  Google Scholar 

  13. Ashby CR, Carr LA, Cook CL, et al. Alteration of 5-HT uptake by plasma fractions in the premenstrual syndrome. J Neural Transm 1990; 79: 41–50

    Article  Google Scholar 

  14. Taylor DL, Mathew RJ, Ho BT, et al. Serotonin levels and platelet uptake during premenstrual tension. Neuropsychobiology 1984; 12: 16–8

    Article  PubMed  CAS  Google Scholar 

  15. Rapkin AJ, Edelmuth E, Chang LC, et al. Whole-blood serotonin in premenstrual syndrome. Obstet Gynecol 1987; 70: 533–7

    PubMed  CAS  Google Scholar 

  16. Malmgren R, Collins A, Nilsson CG. Platelet serotonin uptake and effects of vitamin B6 treatment in premenstrual tension. Neuropsychobiology 1987; 18: 83–8

    Article  PubMed  CAS  Google Scholar 

  17. Rojansky N, Halbreich U, Zander K, et al. Imipramine receptor binding and serotonin uptake in platelets of women with premenstrual changes. Gynecol Obstet Invest 1991; 31: 146–52

    Article  PubMed  CAS  Google Scholar 

  18. Ashby C, Carr LA, Cook CL, et al. Inhibition of serotonin uptake in rat brain synaptosomes by plasma from patients with premenstrual syndrome. Biol Psychiatry 1992; 31: 1169–71

    Article  PubMed  CAS  Google Scholar 

  19. Veehinga A, Westenberg GM. Serotonergic function and late luteal phase dysphoric disorder. Psychopharmacology 1992; 108: 153–8

    Article  Google Scholar 

  20. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 3rd ed. (revised). Washington D.C., American Psychiatric Association, 1987

    Google Scholar 

  21. Bancroft J, Cook A, Davidson D, et al. Blunting of neuroendocrine responses to infusion of L-tryptophan in women with perimenstrual mood change. Psychol Med 1991; 21: 305–12

    Article  PubMed  CAS  Google Scholar 

  22. Rasgon N, McGuire M, Tanavoli S, et al. Neuroendocrine response to an intravenous L-tryptophan challenge in women with premenstrual syndrome. Fertil Steril 2000; 73(1): 144–9

    Article  PubMed  CAS  Google Scholar 

  23. Bancroft J, Cook A. The neuroendocrine response to d-fenfluramine in women with premenstrual depression. J Affect Disord 1995; 36: 57–64

    Article  PubMed  CAS  Google Scholar 

  24. Fitzgerald M, Malone KM, Li S, et al. Blunted serotonin response to fenflurmine challenge in premenstrual dysphoric disorder. Am J Psychiatry 1997; 154; 556–8

    PubMed  CAS  Google Scholar 

  25. Steiner M, Yatham LN, Coote M, et al. Serotonergic dysfunction in women with pure premenstrual dysphoric disorder: Is the fenfluramine challenge test still relevant? Psychiatry Res 1999; 87: 107–15

    Article  PubMed  CAS  Google Scholar 

  26. Yatham LN. Is 5HT1A receptor subsensitivity a trait marker for late luteal phase dysphoric disorder? A pilot study. Can J Psychiatry 1993; 38(10): 662–4

    PubMed  CAS  Google Scholar 

  27. Su TP, Schmidt PJ, Danaceau M, et al. Effect of menstrual cycle phase on neuroendocrine and behavioral responses to the serotonin agonist m-chlorophenylpiperazine in women with premenstrual syndrome and controls. J Clin Endocrinol Metab 1997; 82: 1220–8

    Article  PubMed  CAS  Google Scholar 

  28. Eriksson, E, Allig C, Andersch B, et al. Cerebrospinal fluid levels of monamine metabolites. A preliminary study of their relation to menstrual cycle phase, sex steroids and pituitary hormones in healthy women and in women with premenstrual syndrome. Neuropsychopharmacology 1994; 11(3): 201–13

    CAS  Google Scholar 

  29. Parry BL, Gerner RH, Wilkins JN, et al. CSF and endocrine studies of premenstrual syndrome. Neuropsychopharmacology 1991; 5: 127–37

    PubMed  CAS  Google Scholar 

  30. Parry BL, Berga SL, Kripke DF, et al. Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression. Arch Gen Psychiatry 1990; 47: 1139–46

    Article  PubMed  CAS  Google Scholar 

  31. Parry BL, Berga SL, Mostofi N, et al. Plasma melatonin circadian rhythms during the menstrual cycle and after light therapy in premenstrual dysphoric disorder and normal control subjects. J Biol Rhythms 1997; 12: 47–64

    Article  PubMed  CAS  Google Scholar 

  32. Parry BL, Udell C, Elliott JA, et al. Blunted phase-shift responses to morning bright light in premenstrual dysphoric disorder. J Biol Rhythms 1997; 12(5): 443–56

    PubMed  CAS  Google Scholar 

  33. Kouri EM, Halbreich U. State and trait serotonergic abnormalities in women with dysphoric premenstrual syndromes. Psychopharmacol Bull 1997; 33(4): 767–70

    PubMed  CAS  Google Scholar 

  34. Eriksson E, Lisjo P, Sunblad C, et al. Effect of clomipramine in the premenstrual syndrome. Acta Psych Scand 1990; 81: 87–8

    Article  CAS  Google Scholar 

  35. Rickels K, Freedman EW, Sonderheimer S, et al. Fluoxetine in the treatment of premenstrual syndrome. Curr Ther Res 1990; 48: 161–6

    Google Scholar 

  36. Stone AB, Pearlstein TB, Brown WA. Fluoxetine in the treatment of late luteal phase dysphoric disorder. J Clin Psychiatry 1991; 52: 290–3

    PubMed  CAS  Google Scholar 

  37. Sundblad C, Modigh K, Andersch B, et al. Clomipramine effectively reduces premenstrual irritability and dysphoria: a placebo-controlled trial. Acta Psych Scand 1992; 85: 39–47

    Article  CAS  Google Scholar 

  38. Sundblad C, Hedberg MA, Eriksson E. Clomipramine administered during the luteal phase reduces the symptoms of premenstrual syndrome: a placebo-controlled trial. Neuropsychopharmacology 1993; 9: 133–45

    PubMed  CAS  Google Scholar 

  39. Menkes DB, Taghavi E, Mason PA. Fluoxetine treatment of severe premenstrual syndrome. BMJ 1992; 305: 346–7

    Article  PubMed  CAS  Google Scholar 

  40. Wood SH, Mortoal JF, Chan YF, et al. Treatment of premenstrual syndrome with fluoxetine: a double-blind, placebo-controlled crossover study. Obstet Gynecol 1992; 80: 339–44

    PubMed  CAS  Google Scholar 

  41. Steiner M, Steinberg S, Stewart D, et al. Fluoxetine in the treatment of premenstrual dysphoria. Canadian Fluoxetine/Premenstrual Dysphoria Collaborative Study Group. N Engl J Med 1995; 332: 1529–34

    CAS  Google Scholar 

  42. Ozeren S, Corakci A, Yucesoy I, et al. Fluoxetine in the treatment of premenstrual syndrome. Eur J Obstet Gynecol Reprod Biol 1997; 73: 167–70

    Article  PubMed  CAS  Google Scholar 

  43. Pearlstein TB, Stone AB, Lund SA. Comparison of fluoxetine, bupropion and placebo in the treatment of premenstrual dysphoric disorder. J Clin Psychopharmacol 1997; 17: 261–6

    Article  PubMed  CAS  Google Scholar 

  44. Su TP, Schmidt PJ, Danaceau MA, et al. Fluoxetine in the treatment of premenstrual dysphoria. Neuropsychopharmacology 1997; 16: 346–56

    Article  PubMed  CAS  Google Scholar 

  45. Yonkers KA, Halbreich U, Freeman E, et al. Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. JAMA 1997; 278: 983–8

    CAS  Google Scholar 

  46. Young SA, Hurt PH, Benedek DM, et al. Treatment of premenstrual dysphoric disorder with sertraline during the luteal phase: a randomized, double-blind, placebo-controlled crossover trial. J Clin Psychiatry 1998; 59: 76–80

    Article  PubMed  CAS  Google Scholar 

  47. Eriksson E, Hedberg MA, Andersch B, et al. The serotonin reuptake inhibitor paroxetine is superior to the noradrenaline reuptake inhibitor maprotiline in the treatment of premenstrual syndrome. Neuropsychopharmacology 1995; 12: 167–76

    Article  PubMed  CAS  Google Scholar 

  48. Wikander I, Sundblad C, Andersch B, et al. Citalopram in premenstrual dysphoria: is intermittent treatment during luteal phases more effective than continuous medication throughout the menstrual cycle? J Clin Psychopharmacol 1998; 18: 390–8

    Article  PubMed  CAS  Google Scholar 

  49. Freeman EW, Rickels K, Sondheimer SJ, et al. Nefazadone in the treatment of premenstrual syndrome: a preliminary study. J Clin Psychopharmacol 1994; 14(3): 180–6

    Article  PubMed  CAS  Google Scholar 

  50. Rickels K, Freeman E, Sondheimer S. Buspirone in treatment of premenstrual syndrome. Lancet 1989; I: 777

    Article  Google Scholar 

  51. Brzezinski AA, Wurtman JJ, Wurtman RJ, et al. d-Fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression. Obstet Gynecol 1990; 76: 296–301

    PubMed  CAS  Google Scholar 

  52. Menkes DB, Coates DC, Fawcett P, et al. Acute tryptophan depletion aggravates premenstrual syndrome. J Affect Disord 1994; 32: 37–44

    Article  PubMed  CAS  Google Scholar 

  53. Eriksson E. Serotonin reuptake inhibitors for the treatment of premenstrual dysphoria. Int Clin Psychopharmacol 1999; 14 Suppl. 2: S27–S33

    Google Scholar 

  54. Halbreich U, Smoller JW. Intermittent luteal phase sertraline treatment of dysphoric premenstrual syndrome. J Clin Psychiatry 1997; 58: 399–402

    Article  PubMed  CAS  Google Scholar 

  55. Jermain DM, Preece CK, Sykes RL, et al. Luteal phase sertraline treatment for premenstrual dysphoric disorder. Arch Fam Med 1999; 8: 328–32

    Article  PubMed  CAS  Google Scholar 

  56. Steiner M, Korzekwa M, Lamont J, et al. Intermittent fluoxetine dosing in the treatment of women with premenstrual dysphoria. Psychopharmacol Bull 1997; 33(4): 771–4

    PubMed  CAS  Google Scholar 

  57. Dimmock PW, Wyatt KM, Jones PW, et al. Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review. Lancet 2000; 356: 1131–6

    Article  PubMed  CAS  Google Scholar 

  58. Freeman EW, Rickels K, Sondheimer SJ, et al. Differential response to antidepressants in women with premenstrual syndrome/premenstrual dysphoric disorder. Arch Gen Psychiatry 1999; 56: 932–9

    Article  PubMed  CAS  Google Scholar 

  59. Taghavi E, Menkes DB, Howard RC, et al. Premenstrual syndrome: a double-blind controlled trial of desipramine and methylscopolamine. Int Clin Psycopharmacol 1995; 10: 119–22

    Article  CAS  Google Scholar 

  60. Steinberg S, Annable L, Young SN, et al. A placebo-controlled clinical trial of L-tryptophan in premenstrual dysphoria. Biol Psychiatry 1999; 45: 313–20

    Article  PubMed  CAS  Google Scholar 

  61. Elks ML. Open trial of fluoxetine therapy for premenstrual syndrome. South Med J 1993; 86: 503–7

    Article  PubMed  CAS  Google Scholar 

  62. Pearlstein TB, Stone AB. Long-term fluoxetine treatment of late luteal phase dysphoric disorder. J Clin Psychiatry 1994; 55: 332–5

    PubMed  CAS  Google Scholar 

  63. Freeman EW, Rickels K, Sondheimer SJ, et al. Nefazadone in the treatment of premenstrual syndrome: a preliminary study. J Clin Psychopharmacol 1994; 14: 180–6

    Article  PubMed  CAS  Google Scholar 

  64. Sundblad C, Wikander I, Andersch B, et al. A naturalistic study of paroxetine in premenstrual syndrome: efficacy and side-effects during ten cycles of treatment. Eur Neuropsychopharmacol 1997; 7: 201–6

    Article  PubMed  CAS  Google Scholar 

  65. Sundstrom I, Backstrom T. Citalopram increases pregnanolone sensitivity in patients with premenstrual syndrome: an open trial. Psychoneuroendocrinology 1998; 23(1): 73–88

    Article  PubMed  CAS  Google Scholar 

  66. Steiner M, Pearlstein T. Premenstrual dysphoria and the serotonin system: pathophysiology and treatment. J Clin Psychiatry 2000; 61 Suppl. 12: 17–21

    Google Scholar 

  67. Cabib S, Orsini C, Le Moal M, et al. Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experience. Science 2000; 289: 463-5

    Article  PubMed  CAS  Google Scholar 

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  1. University of California, San Diego, 9500 Gilman Dr., La Jolla, California, 92093-0804, USA

    Barbara L. Parry

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Parry, B.L. The Role of Central Serotonergic Dysfunction in the Aetiology of Premenstrual Dysphoric Disorder. Mol Diag Ther 15, 277–285 (2001). https://doi.org/10.2165/00023210-200115040-00003

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