Neuroesteroides e esquizofrenia: a função do estrogênio e da progesterona na modulação e proteção do cérebro
DOI:
https://doi.org/10.25118/2763-9037.2019.v9.64Palavras-chave:
Mulheres, esquizofrenia, neuroesteroides, estrogênio e progesteronaResumo
A esquizofrenia é uma psicose crônica, debilitante, de origem multifatorial, que apresenta em sua fisiopatologia pelo menos três mecanismos conhecidos: a desregulação dopaminérgica, a perturbação da neurotransmissão glutamatérgica e GABAérgica e o estado pró-inflamatório do cérebro. Existem diferenças marcantes entre os gêneros na esquizofrenia, e muitos autores afirmam que os hormônios sexuais podem influenciar o curso e os sintomas da doença, modulando a sua gravidade. Os neuroesteroides são neuro-hormônios que têm a capacidade de modular a expressão de subunidades de receptores GABAérgicos subtipo A e N-metil D-aspartato, desempenhando um papel crucial na fisiopatologia de vários transtornos psiquiátricos. O objetivo deste artigo é investigar o quanto os neuroesteroides podem influenciar na fisiopatologia da esquizofrenia em mulheres, através de uma revisão de literatura onde foram incluídos estudos pré-clínicos, clínicos e moleculares que investigaram os efeitos do estrogênio e da progesterona na modulação e proteção do sistema nervoso central (SNC), discutindo a sua função como possíveis adjuvantes terapêuticos no tratamento da esquizofrenia.
Downloads
Métricas
Referências
Searles S, Makarewicz JA, Dumas JA. The role of estradiol in schizophrenia diagnosis and symptoms in postmenopausal women. Schizophr Res. 2018;196:35-8. DOI: https://doi.org/10.1016/j.schres.2017.05.024
Londero MDB, Massuda R, Gama CS. Neurobiologia da esquizofrenia. In: Antônio Egídio Narde, João Quevedo, Antônio Geraldo da Silva. Esquizofrenia. Porto Alegre: Artmed; 2015. p. 45-51.
Sun J, Walker AJ, Dean B, van den Buuse M, Gogos A. Progesterone: the neglected hormone in schizophrenia? A focus on progesterone-dopamine interacti ons. Psychoneuroendocrinology. 2016;74:126-40. DOI: https://doi.org/10.1016/j.psyneuen.2016.08.019
Kahn RS, Sommer IE. The neurobiology and treatment of fi rst episode schizophrenia. Mol Psychiatry. 2015;20:84-97. DOI: https://doi.org/10.1038/mp.2014.66
Castle DJ. Diferenças Sexuais do cérebro e esquizofrenia. In: Castle DJ, Mcgrath J, Kulkarni J. As mulheres e a esquizofrenia. Lisboa: CLIMEPSI; 2003. p. 21-32.
Hafner H. Gender diff erences in schizophrenia. Psychoneuroendocrinology. 2003;28:17-54. DOI: https://doi.org/10.1016/S0306-4530(02)00125-7
McGregor C, Riordan A, Thornton J. Estrogens and the cogniti ve symptoms of schizophrenia: possible neuroprotecti ve mechanisms. Front Neuroendocrinol. 2017;47:19-33. DOI: https://doi.org/10.1016/j.yfrne.2017.06.003
Gogos A, Sbisa AM, Sun J, Gibbons A, Udawela M, Dean B. A role for estrogen in schizophrenia: clinical and preclinical fi ndings. Int J Endocrinol. 2015;2015:615356. DOI: https://doi.org/10.1155/2015/615356
Ji E, Weickert CS, Lenroot R, Kindler J, Skilleter AJ, Vercammen A, et al. Adjuncti ve selecti ve estrogen receptor modulator increases neural acti vity in the hippocampus and inferior frontal gyrus during emoti onal face recogniti on in schizophrenia. Transl Psychiatry. 2016;6:e795. DOI: https://doi.org/10.1038/tp.2016.59
Compagnone NA, Mellon SH. Neurosteroids: biosynthesis and functi on of these novel neuromodulators. Front Neuroendocrinol. 2000;21:1-56. DOI: https://doi.org/10.1006/frne.1999.0188
Strous RD, Spivak B, Yoran-Hegesh R, Maayan R, Averbuch E, Kotler M, et al. Analysis of neurosteroid levels in att enti on defi cit hyperacti vity disorder. Int J Neuropsychopharmacol. 2001;4:259-64. DOI: https://doi.org/10.1017/S1461145701002462
Behl C. Estrogen can protect neurons: modes of acti on. J Steroid Biochem Mol Biol. 2003;83:95-97.
Woolley CS. Acute eff ects of estrogen on neuronal physiology. Annu Rev Pharmacol Toxicol. 2007;47:657-80. DOI: https://doi.org/10.1146/annurev.pharmtox.47.120505.105219
MacKenzie EM, Odontiadis J, Le Mellédo JM, Prior TI, Baker GB. The relevance of neuroactive steroids in schizophrenia, depression, and anxiety disorders. Cell Mol Neurobiol. 2007;27:541-74. DOI: https://doi.org/10.1007/s10571-006-9086-0
Longone P, Rupprecht R, Manieri GA, Bernardi G, Romeo E, Pasini A. The complex roles of neurosteroids in depression and anxiety disorders. Neurochem Int. 2008;52:596-601. DOI: https://doi.org/10.1016/j.neuint.2007.10.001
Do Rego JL, Seong JY, Burel D, Leprince J, Luu- The V, Tsutsui K, et al. Neurosteroid biosynthesis: enzymatic pathways and neuroendocrine regulation by neurotransmitters and neuropeptides. Front Neuroendocrinol. 2009;30:259-301. DOI: https://doi.org/10.1016/j.yfrne.2009.05.006
Luchetti S, Huitinga I, Swaab DF. Neurosteroid and GABA-A receptor alterations in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Neuroscience. 2011;191:6-21. DOI: https://doi.org/10.1016/j.neuroscience.2011.04.010
Oberlander JG, Woolley CS. 17β-estradiol acutely potentiates glutamatergic synaptic transmission in the hippocampus through distinct mechanisms in males and females. J Neurosci. 2016;36:2677-90. DOI: https://doi.org/10.1523/JNEUROSCI.4437-15.2016
Cai H, Cao T, Zhou X, Yao JK. Neurosteroids in schizophrenia: pathogenic and therapeutic implications. Front Psychiatry. 2018;9:73. DOI: https://doi.org/10.3389/fpsyt.2018.00073
Miller KK. Neuroactive steroids and depression. In: Shapero B, Mischoulon D, Cusin C. The Massachusetts general hospital guide to depression. Basileia: Springer Nature Switzerland; 2019. p. 147-51. DOI: https://doi.org/10.1007/978-3-319-97241-1_11
Robel P, Baulieu EE. Neurosteroids: biosynthesis and function. Trends Endocrinol Metab. 1994;5:1-8. DOI: https://doi.org/10.1016/1043-2760(94)90114-7
Sthal SM. Psicose e esquizofrenia. In: Sthal SM. Psicofarmacologia: bases neurocientíficas e aplicações práticas. 4ª ed. Rio de Janeiro: Guanabara Koogan; 2016. p. 130-199.
da Silva RCB. Esquizofrenia: uma revisão. Psicol USP. 2006;17:263-85. DOI: https://doi.org/10.1590/S0103-65642006000400014
Remington G, Foussias G, Agid O, Fervaha G, Takeuchi H, Hahn M. The neurobiology of relapse in schizophrenia. Schizophr Res. 2014;152:381-90. DOI: https://doi.org/10.1016/j.schres.2013.10.009
Chávez-Castillo M, Núñez V, Nava M, Ortega A, Rojas M, Bermúdez V, et al. Depression as a neuroendocrine disorder: emerging neuropsychopharmacological approaches beyond monoamines. Adv Pharmacol Sci. 2019;2019;7943481. DOI: https://doi.org/10.1155/2019/7943481
Krystal JH, Anand A, Moghaddam B. Effects of NMDA receptor antagonists: implications for the pathophysiology of schizophrenia. Arch Gen Psychiatry. 2002;59:663-4. DOI: https://doi.org/10.1001/archpsyc.59.7.663
Schwartz TL, Sachdeva S, Stahl SM. Genetic data supporting the NMDA glutamate receptor hypothesis for schizophrenia. Curr Pharm Des. 2012;18;1580-92. DOI: https://doi.org/10.2174/138161212799958594
Wang M, Yang Y, Wang CJ, Gamo NJ, Jin LE, Mazer JA, et al. NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex. Neuron. 2013;77:736-49. DOI: https://doi.org/10.1016/j.neuron.2012.12.032
El-Khodor BF, Flores G, Srivastava LK, Boksa P. Effects of birth insult and stress at adulthood on excitatory amino acid receptors in adult rat brain. Synapse. 2004;54:138-46. DOI: https://doi.org/10.1002/syn.20073
Kaur C, Sivakumar V, Ang LS, Sundaresan A. Hypoxic damage to the periventricular white matter in neonatal brain: role of vascular endothelial growth factor, nitric oxide and excitotoxicity. J Neurochem. 2006:98:1200-16. DOI: https://doi.org/10.1111/j.1471-4159.2006.03964.x
Samuelsson AM, Jennische E, Hansson HA, Holmäng A. Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1345-56. DOI: https://doi.org/10.1152/ajpregu.00268.2005
Canetta SE, Brown AS. Prenatal infection, maternal immune activation, and risk for schizophrenia. Transl Neurosci. 2012;3:320-7. DOI: https://doi.org/10.2478/s13380-012-0045-6
Hagberg H, Gressens P, Mallard C. Inflammation during fetal and neonatal life: implications for neurologic and neuropsychiatric disease in children and adults. Ann Neurol. 2012;71:444-57. DOI: https://doi.org/10.1002/ana.22620
Monji A, Kato T, Kanba S. Cytokines and schizophrenia: microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009;63:257-65. DOI: https://doi.org/10.1111/j.1440-1819.2009.01945.x
Papadia S, Soriano FX, Leveille F, Martel MA, Dakin KA, Hansen HH, et al. Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses. Nat Neurosci. 2008;11:476-87. DOI: https://doi.org/10.1038/nn2071
King SR. Neurosteroids and the nervous system. Basileia: SpringerBriefs in Neuroscience; 2013. DOI: https://doi.org/10.1007/978-1-4614-5559-2
Cai H, Zhou X, Dougherty GG, Reddy RD, Haas GL, Montrose DM, et al. Pregnenoloneprogesterone allopregnanolone pathway as a potenti al therapeuti c target in fi rst-episode anti psychoti c-naïve pati ents with schizophrenia. Psychoneuroendocrinology. 2018;90:43-51. DOI: https://doi.org/10.1016/j.psyneuen.2018.02.004
McEwen BS. Non-genomic and genomic eff ects of steroids on neural acti vity. Trends Pharmacol Sci. 1991;12:141-7. DOI: https://doi.org/10.1016/0165-6147(91)90531-V
Baulieu EE. Neurosteroids: of the nervous system, by the nervous system, for the nervous system. Recent Prog Horm Res. 1997;52:1-32.
Wang M. Neurosteroids and GABA-A receptor functi on. Front Endocrinol (Lausanne). 2011;2:44. DOI: https://doi.org/10.3389/fendo.2011.00044
Carver CM, Reddy DS. Neurosteroid interacti ons with synapti c and extrasynapti c GABA (A) receptors: regulati on of subunit plasti city, phasic and tonic inhibiti on, and neuronal network excitability. Psychopharmacology (Berl). 013;230:151-88. DOI: https://doi.org/10.1007/s00213-013-3276-5
Reddy DS, Estes WA. Clinical potenti al of neurosteroids for CNS disorders. Trends Pharmacol Sci. 2016;7:543-61. DOI: https://doi.org/10.1016/j.tips.2016.04.003
Uusi-Oukari M, Korpi ER. Regulati on of GABA-A receptor subunit expression by pharmacological agents. Pharmacol Rev. 2010;62:97-135. DOI: https://doi.org/10.1124/pr.109.002063
Hosie AM, Clarke L, da Silva H, Smart TG. Conserved site for neurosteroid modulati on of GABA A receptors. Neuropharmacology. 2009;56:149-54. DOI: https://doi.org/10.1016/j.neuropharm.2008.07.050
Reddy DS. Neurosteroids: endogenous role in the human brain and therapeuti c potenti als. Prog Brain Res. 2010;186:113-37. DOI: https://doi.org/10.1016/B978-0-444-53630-3.00008-7
Shen W, Mennerick S, Covey DF, Zorumski CF. Pregnenolone sulfate modulates inhibitory synapti c transmission by enhancing GABA (A) receptor desensiti zati on. J Neurosci. 2000;20:3571-9. DOI: https://doi.org/10.1523/JNEUROSCI.20-10-03571.2000
Lambert JJ, Belelli D, Peden DR, Vardy AW, Peters JA. Neurosteroid modulati on of GABAA receptors. Prog Neurobiol. 2003;71:67-80. DOI: https://doi.org/10.1016/j.pneurobio.2003.09.001
Castle D, Sham P, Murray R. Diff erences in distributi on of ages of onset in males and females with schizophrenia. Schizophr Res. 1998;33:179-83. DOI: https://doi.org/10.1016/S0920-9964(98)00070-X
Seeman MV. Menstrual exacerbati on of schizophrenia symptoms. Acta Psychiatr Scand. 2012;125:363-71. DOI: https://doi.org/10.1111/j.1600-0447.2011.01822.x
Seeman MV. Gender diff erences in the prescribing of anti psychoti c drugs. Am J Psychiatry. 2004;161:1324-33. DOI: https://doi.org/10.1176/appi.ajp.161.8.1324
Usall J, Suarez D, Haro JM; SOHO Study Group. Gender diff erences in response to anti psychoti c treatment in outpati ents with schizophrenia. Psychiatry Res. 2007;153:225-31. DOI: https://doi.org/10.1016/j.psychres.2006.09.016
Gogos A, Ney, LJ, Seymour N, Van Rheenen TE, Felmingham KL. Sex diff erences in schizophrenia, bipolar disorder, and postt raumati c stress disorder: are gonadal hormones the link? Br J Pharmacol. 2019 Jan 18. doi: 10.1111/bph.14584. [Epub ahead of print] DOI: https://doi.org/10.1111/bph.14584
Bassit DP, Neto MRL. Relação entre data de admissão hospitalar e período do ciclo menstrual de mulheres com diagnósti co de esquizofrenia. Rev Bras Psiquiatr. 2000;22:57-61. DOI: https://doi.org/10.1590/S1516-44462000000200005
Andrade LHSG, Viana MC, Silveira CM. Epidemiologia dos transtornos psiquiátricos na mulher. Rev Psiquiatr Clin. 2006;33:43-54. DOI: https://doi.org/10.1590/S0101-60832006000200003
Riecher-Rössler A. Oestrogens, prolacti n, hypothalamic-pituitary-gonadal axis, and schizophrenic psychoses. Lancet Psychiatry. 2017;4:63-72. DOI: https://doi.org/10.1016/S2215-0366(16)30379-0
Locci A, Pinna G. Neurosteroid biosynthesis down-regulati on and changes in GABAA receptor subunit compositi on: a biomarker axis in stressinduced cogniti ve and emoti onal impairment. Br J Pharmacol. 2017;174:3226-41. DOI: https://doi.org/10.1111/bph.13843
Riecher-Rössler A, Butler S, Kulkarni J. Sex and gender diff erences in schizophrenic psychoses-a criti cal review. Arch Womens Ment Health. 2018;21:627-48. DOI: https://doi.org/10.1007/s00737-018-0847-9
Di Paolo T, Lévesque D, Daigle M. A physiological dose of progesterone aff ects rat striatum biogenic amine metabolism. Eur J Pharmacol. 1986;125:11-6. DOI: https://doi.org/10.1016/0014-2999(86)90077-4
Laconi MR, Cabrera RJ. Eff ect of centrally injected allopregnanolone on sexual recepti vity, luteinizing hormone release, hypothalamic dopamineturnover, and release in female rats. Endocrine. 2002;17:77-83. DOI: https://doi.org/10.1385/ENDO:17:2:077
Motzo C, Porceddu ML, Maira G, Flore G, Concas A, Dazzi L. Inhibition of basal and stress-induced dopamine release in the cerebral cortex and nucleus accumbens of freely moving rats by the neurosteroid allopregnanolone. J Psychopharmacol. 1996;10:266-72. DOI: https://doi.org/10.1177/026988119601000402
Adams JM, Thomas P, Smart TG. Modulation of neurosteroid potentiation by protein kinases at synaptic-and extrasynaptic-type GABAA receptors. Neuropharmacology. 2015;88:63-73. DOI: https://doi.org/10.1016/j.neuropharm.2014.09.021
Tenn CC, Niles LP. Sensitization of G proteincoupled benzodiazepine receptors in the striatum of 6-hydroxydopamine-lesioned rats. J Neurochem. 1997;69:1920-6. DOI: https://doi.org/10.1046/j.1471-4159.1997.69051920.x
Rougé-Pont F, Mayo W, Marinelli M, Gingras M, Le Moal M, Piazza PV. The neurosteroid allopregnanolone increases dopamine release and dopaminergic response to morphine in the rat nucleus accumbens. Eur J Neurosci. 2002;16:169-73. DOI: https://doi.org/10.1046/j.1460-9568.2002.02084.x
Brandon N, Jovanovic J, Moss S. Multiple roles of protein kinases in the modulation of γ-aminobutyric acid(A) receptor function and cell surface expression. Pharmacol Ther. 2002;94:113-22. DOI: https://doi.org/10.1016/S0163-7258(02)00175-4
Singer CA, Rogers KL, Strickland TM, Dorsa DM. Estrogen protects primary cortical neurons from glutamate toxicity. Neurosci Lett. 1996;212:13-6. DOI: https://doi.org/10.1016/0304-3940(96)12760-9
Sribnick EA, Ray SK, Nowak MW, Li L, Banik NL. 17beta-estradiol attenuates glutamate-induced apoptosis and preserves electrophysiologic function in primary cortical neurons. J Neurosci Res. 2004;76:688-96. DOI: https://doi.org/10.1002/jnr.20124
Spampinato SF, Merlo S, Molinaro G, Battaglia G, Bruno V, Nicoletti F, et al. Dual effect of 17beta estradiol on NMDA-induced neuronal death: involvement of metabotropic glutamate receptor 1. Endocrinology. 2012;153:5940-8. DOI: https://doi.org/10.1210/en.2012-1799
Velíšková J, De Jesus G, Kaur R, Velíšek L. Females, their estrogens and seizures. Epilepsia. 2010;51:141-4. DOI: https://doi.org/10.1111/j.1528-1167.2010.02629.x
Wang LJ, Lee SY, Choua MC, Lee MJ, Chou WJ. Dehydroepiandrosterone sulfate, free testosterone, and sex hormone-binding globulin on susceptibility to attention-deficit/hyperactivity disorder. Psychoneuroendocrinology. 2019;103:212-8. DOI: https://doi.org/10.1016/j.psyneuen.2019.01.025
Seeman MV. Treating schizophrenia at the time of menopause. Maturitas. 2012;72:117-20. DOI: https://doi.org/10.1016/j.maturitas.2012.03.008
Culmsee C, Vedder H, Ravati A, Junker V, Otto D, Ahlemeyer B, et al. Neuroprotection by estrogens in a mouse model of focal cerebral ischemia and in cultured neurons: evidence for a receptorindependent antioxidative mechanism. J Cereb Blood Flow Metab. 1999;19:263-9. DOI: https://doi.org/10.1097/00004647-199911000-00011
Moosmann B, Behl C. The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proc Natl Acad Sci U S A. 1999;96:8867-72. DOI: https://doi.org/10.1073/pnas.96.16.8867
Kirkpatrick B, Miller BJ. Inflammation and schizophrenia. Schizophr Bull. 2013;39:1174-9. DOI: https://doi.org/10.1093/schbul/sbt141
Feigenson KA, Kusnecov AW, Silverstein SM. Inflammation and the two-hit hypothesis of schizophrenia. Neurosci Biobehav Rev. 2014;38:72-93. DOI: https://doi.org/10.1016/j.neubiorev.2013.11.006
Adamski J, Ma Z, Nozell S, Benveniste EN. 17betaestradiol inhibits class II major histocompatibility complex (MHC) expression: influence on histone modifications and CBP recruitment to the class II MHC promoter. Mol Endocrinol. 2004;18:1963-74. DOI: https://doi.org/10.1210/me.2004-0098
Xing D, Oparil S, Yu H, Gong K, Feng W, Black J, et al. Estrogen modulates NFκB signaling by enhancing IκBα levels and blocking p65 binding at the promoters of inflammatory genes via estrogen receptor-β. PLoS One. 2012;7:e36890. DOI: https://doi.org/10.1371/journal.pone.0036890
Paimela T, Ryhänen T, Mannermaa E, Ojala J, Kalesnykas G, Salminen A, et al. The effect of 17β-estradiol on IL-6 secretion and NF-κB DNAbinding activity in human retinal pigment epithelial cells. Immunol Lett. 2007;110:139-44. DOI: https://doi.org/10.1016/j.imlet.2007.04.008
Ospina JA, Brevig HN, Krause DN, Duckles SP. Estrogen suppresses IL-1beta-mediated induction of COX-2 pathway in rat cerebral blood vessels. Am J Physiol Heart Circ Physiol. 2004;286:H2010-9. DOI: https://doi.org/10.1152/ajpheart.00481.2003
Sarvari M, Kallo I, Hrabovszky E, Solymosi N, Liposits Z. Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innateimmune system of the hippocampus in middle aged female rats. PLoS One. 2014;9:e88540. DOI: https://doi.org/10.1371/journal.pone.0088540
Lopez Rodriguez AB, Mateos Vicente B, Romero-Zerbo SY, Rodriguez-Rodriguez N, Bellini MJ, Rodriguez de Fonseca F, et al. Estradiol decreases corti cal reacti ve astrogliosis aft er brain injury by a mechanism involving cannabinoid receptors. Cereb Cortex. 2011;21:2046-55. DOI: https://doi.org/10.1093/cercor/bhq277
Akabori H, Moeinpour F, Bland KI, Chaudry IH. Mechanism of the anti -infl ammatory eff ect of 17beta-estradiol on brain following traumahemorrhage. Shock. 2010;33:43-8. DOI: https://doi.org/10.1097/SHK.0b013e3181b0ebcb
Kulkarni J, de Castella A, Smith D, Taff e J, Keks N, Copolov D. A clinical trial of the eff ects of estrogen in acutely psychoti c women. Schizophr Res. 1996;20:247-52. DOI: https://doi.org/10.1016/0920-9964(96)82949-5
Ahokas A, Aito M, Turiainen S. Associati on between oestradiol and puerperal psychosis. Acta Psychiatr Scand. 2000;101:167-9; discussion 169-70. DOI: https://doi.org/10.1034/j.1600-0447.2000.96005.x
Kulkarni J, Riedel A, de Castella AR, Fitzgerald PB, Rolfe TJ, Taff e J, et al. A clinical trial of adjuncti ve oestrogen treatment in women with schizophrenia. Arch Womens Ment Health. 2002;5:99-104. DOI: https://doi.org/10.1007/s00737-002-0001-5
Akhondzadeh S, Nejati safa AA, Amini H, Mohammadi MR, Larijani B, Kashani L, et al. Adjuncti ve estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:1007-12. DOI: https://doi.org/10.1016/S0278-5846(03)00161-1
Kulkarni J, Fink G. Hormonas e psicose. In: Castle DJ, Mcgrath J, Kulkarni J. As mulheres e a esquizofrenia. Lisboa: CLIMEPSI; 2003. p. 57-68.
Kulkarni J, de Castella A, Fitzgerald PB, Gurvich CT, Bailey M, Bartholomeusz C, et al. Estrogen in severe mental illness: a potenti al new treatment approach. Arch Gen Psychiatry. 2008;65:955-60. DOI: https://doi.org/10.1001/archpsyc.65.8.955
Kulkarni J, Gavrilidis E, Wang W, Worsley R, Fitzgerald PB, Gurvich C, et al. Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of childbearing age. Mol Psychiatry. 2014;20:695-702. DOI: https://doi.org/10.1038/mp.2014.33
Lindamer LA, Buse DC, Lohr JB, Jeste DV. Hormone replacement therapy in postmenopausal women with schizophrenia: positi ve eff ect on negati ve symptoms? Biol Psychiatry. 2001;49:47-51. DOI: https://doi.org/10.1016/S0006-3223(00)00995-1
Ritsner MS. Pregnenolone, dehydroepiandrosterone, and schizophrenia: alterati ons and clinical trials. CNS Neurosci Ther. 2010;16:32-44. DOI: https://doi.org/10.1111/j.1755-5949.2009.00118.x
Louza MR, Marques AP, Elkis H, Bassitt D, Diegoli M, Gatt az WF. Conjugated estrogens as adjuvant therapy in the treatment of acute schizophrenia: a double-blind study. Schizophr Res. 2004;66:97-100. DOI: https://doi.org/10.1016/S0920-9964(03)00082-3
Ghafari E, Fararouie M, Shirazi H, Farhangfar A, Ghaderi F, Mohammadi A. Combinati on of estrogen and anti psychoti cs in the treatment of women with chronic schizophrenia: a doubleblind, randomized, placebo-controlled clinical trial. Clin Schizophr Relat Psychoses. 2013;6:172-6. DOI: https://doi.org/10.3371/CSRP.GHFA.01062013
Ko YH, Joe SH, Cho W, Park JH, Lee JJ, Jung IK, et al. Eff ect of hormone replacement therapy on cogniti ve functi on in women with chronic schizophrenia. Int J Psychiatry Clin Pract. 2006;10:97-104. DOI: https://doi.org/10.1080/13651500500526235
Bergemann N, Mundt C, Parzer P, Jannakos I, Nagl I, Salbach B, et al. Plasma concentrati ons of estradiol in women suff ering from schizophrenia treated with conventi onal versus atypical anti psychoti cs. Schizophr Res. 2005;73:357-66. DOI: https://doi.org/10.1016/j.schres.2004.06.013
Baxter MG, Roberts MT, Gee NA, Lasley BL, Morrison JH, Rapp PR. Multi ple clinically relevant hormone therapy regimens fail to improve cogniti ve functi on in aged ovariectomized rhesus monkeys. Neurobiol Aging. 2013;34:1882-90. DOI: https://doi.org/10.1016/j.neurobiolaging.2012.12.017
Nilsen J, Brinton RD. Impact of progesti ns on estrogen-induced neuroprotecti on: synergy by progesterone and 19 morprogesterone and antagonism by medroxyprogesterone acetate. Endocrinology. 2002;143:205-12. DOI: https://doi.org/10.1210/endo.143.1.8582
Fitzgerald P, Seeman MV. Implicações terapêuti cas. In: Castle DJ, Mcgrath J. Kulkarni J. As Mulheres e a esquizofrenia. Lisboa: CLIMEPSI; 2003. p. 93-104.
Chlebowski RT, Kuller LH, Prenti ce RL, Stefanick ML, Manson JE, Gass M, et al. Breast cancer aft eruse of estrogen plus progesti n in postmenopausal women. N Engl J Med. 2009;360:573-87. DOI: https://doi.org/10.1056/NEJMoa0807684
Cyr M, Calon F, Morissett e M, Grandbois M, Di Paolo T, Callier S. Drugs with estrogen-like potency and brain acti vity: potenti al therapeuti c applicati on for the CNS. Curr Pharm Des. 2000;6:1287-312. DOI: https://doi.org/10.2174/1381612003399725
Kulkarni J, Gurvich C, Lee SJ, Gilbert H, Gavrilidis E, de Castella A, et al. Piloti ng the eff ecti ve therapeuti c dose of adjuncti ve selecti ve estrogen receptor modulator treatment in postmenopausal women with schizophrenia. Psychoneuroendocrinology. 2010;35:1142-7. DOI: https://doi.org/10.1016/j.psyneuen.2010.01.014
Usall J, Huerta-Ramos E, Iniesta R, Cobo J, Araya S, Roca M, et al. Raloxifene as an adjuncti ve treatment for postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2011;72:1552-7. DOI: https://doi.org/10.4088/JCP.10m06610
Khodaie-Ardakani MR, Khosravi M, Zarinfard R, Nejati S, Mohsenian A, Tabrizi M, et al. A placebocontrolled study of raloxifene added to risperidone in men with chronic schizophrenia. Acta Med Iran. 2015;53:337-45.
Kulkarni J, Gavrilidis E, Gwini SM Worsley R, Grigg J, Warren A, et al. Eff ect of adjuncti ve raloxifene therapy on severity of refractory schizophrenia in women: a randomized clinical trial. JAMA Psychiatry. 2016;73:947-54. DOI: https://doi.org/10.1001/jamapsychiatry.2016.1383
Usall J, Huerta-Ramos E, Labad J, Cobo J, Nunez C, Creus M, et al. Raloxifene as an adjuncti ve treatment for postmenopausal women with schizophrenia: a 24-week double-blind, randomized, parallel, placebo-controlled trial. Schizophr Bull. 2016;42:309-17. DOI: https://doi.org/10.1093/schbul/sbv149
Weiser M, Levi L, Burshtein S, Hagin M, Matei VP, Podea D, et al. Raloxifene plus anti psychoti cs versus placebo plus anti psychoti cs in severely Ill decompensated postmenopausal women with schizophrenia or schizoaff ecti ve disorder: a randomized controlled trial. J Clin Psychiatry. 2017;78:e758-e65. DOI: https://doi.org/10.4088/JCP.15m10498
Huerta-Ramos E, Iniesta R, Ochoa S, Cobo J, Miquel E, Roca M, et al. Eff ects of raloxifene on cogniti on in postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2014;24:223-31. DOI: https://doi.org/10.1016/j.euroneuro.2013.11.012
Berent-Spillson A, Briceno E, Pinsky A, Simmen A, Persad CC, Zubieta JK, et al. Disti nct cogniti ve eff ects of estrogen and progesterone in menopausal women. Psychoneuroendocrinology. 2015;59:25-36. DOI: https://doi.org/10.1016/j.psyneuen.2015.04.020
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Este trabalho está licenciado sob uma licença Creative Commons Attribution-NonCommercial 4.0 International License.
Debates em Psiquiatria permite que o (s) autor (es) mantenha(m) seus direitos autorais sem restrições. Atribuição-NãoComercial 4.0 Internacional (CC BY-NC 4.0) - Debates em Psiquiatria é regida pela licença CC-BY-NC
