A DESREGULAÇÃO DE PROGESTERONA E SEU EFEITO NOS RECEPTORES GABA-A NO TRANSTORNO DISFÓRICO PRÉ-MENSTRUAL
Resumo
O transtorno disfórico pré-menstrual (TDPM) é um transtorno psiquiátrico que envolve os hormônios ovarianos que acomete o ciclo GABAérgico do sistema nervoso central da mulher. A partir de um estudo qualitativo, foi levantada uma pesquisa sobre o funcionamento fisiopatológico da doença. Os principais aspectos desenvolvidos foram a ação bimodal da alopregnanolona, a hipótese de tolerância dos receptores GABAA e o uso de progesterona como tratamento da doença. Os resultados da pesquisa indicam que a suplementação de progesterona contribui de maneira agravante à doença, aumentando os sintomas negativos e sendo contraindicada para o tratamento do TDPM.
Referências
ABI-SAAB, W.M.; BUBSER, M.; ROTH, R.H.; DEUTCH, A.Y. 5-HT2 Receptor Regulation of Extracellular GABA Levels in the Prefrontal Cortex. Neuropsychopharmacology, v. 20, n. 1, p. 92-96, 1999. https://doi.org/10.1016/S0893-133X(98)00046-3
ANDRÉEN, L.; SUNDSTRÖM-POROMAA, I.; BIXO, M.; ANDERSSON, M.; NYBERG, S.; BÄCKSTRÖM, T. Relationship Between Allopregnanolone and Negative Mood in Postmenopausal Women Taking Sequential Hormone Replacement Therapy with Vaginal Progesterone. Psychoneuroendocrinology, v. 30, n. 2, p. 212-224, 2005. https://doi.org/10.1016/j.psyneuen.2004.07.003
ASSOCIAÇÃO AMERICANA DE PSIQUIATRIA. Manual Diagnóstico e Estatístico de Transtornos Mentais - DSM-5, 5ª. edição. Washington DC: AMERICAN PSYCHIATRIC ASSOCIATION PRESS, 2014.
BEAUCHAMP, M.H.; ORMEROD, B.K.; JHAMANDAS, K.; BOEGMAN, R.J.; BENINGER, R.J. Neurosteroids and Reward: Allopregnanolone Produces a Conditioned Place Aversion in Rats. Pharmacology Biochemistry and Behavior, v. 67, n.1, p. 29-35, 2000. https://doi.org/10.1016/s0091-3057(00)00299-9
BHATIA, S. C.; BHATIA, S. K. Diagnosis and Treatment of Premenstrual Dysphoric Disorder. American Family Physician, v. 66, n. 7, p. 1239-1248, 2002.
CARL, P.; HÖGSKILDE, S.; NIELSEN, J.W.; SÖRENSEN, M.B.; LINDHOLM, M.; KARLEN, B.; BÄCKSTRÖM, T. Pregnanolone Emulsion: A Preliminary Pharmacokinetic and Pharmacodynamic Study of a New Intravenous Anaesthetic Agent. Anaesthesia, v. 45, n. 3, p. 189-197, 1990. https://doi.org/10.1111/j.1365-2044.1990.tb14683.x
DUCASSE, D.; JAUSSENT, I.; OLIÉ, E.; GUILLAUME, S.; LOPEZ-CASTROMAN, J.; COURTET, P. Personality Traits of Suicidality Are Associated with Premenstrual Syndrome and Premenstrual Dysphoric Disorder in a Suicidal Women Sample. PLOS ONE, v. 11, n. 2, e0148653, 2016. https://doi.org/10.1371/journal.pone.0148653
GUERRA-ARAIZA, C.; MIRANDA-MARTINEZ, A.; NERI-GOMÉZ, T.; CAMACHO-ARROYO, I. Sex Steroids Effects on the Content of GAD, TH, GABAA, and Glutamate Receptors in the Olfactory Bulb of the Male Rat. Neurochemical Research, v. 33, n. 8, p. 1568-1573, 2008. https://doi.org/10.1007/s11064-008-9665-1
GULINELLO, M.; GONG, Q.H.; LI, X.; SMITH, S.S. Short-term Exposure to a Neuroactive Steroid Increases α4 GABAA Receptor Subunit Levels in Association with Increased Anxiety in the Female Rat. Brain Research, v. 910, n. 0, p. 55-66, 2001.
JAKAB, R.L.; GOLDMAN-RAKIC, P.S. Segregation of Serotonin 5-HT2A and 5-HT3 Receptors in Inhibitory Circuits of the Primate Cerebral Cortex. The Journal of Comparative Neurology, v. 417, n. 3, p. 337-348, 2000. https://doi.org/10.1002/(sici)1096-9861(20000214)417:3%3C337::aid-cne7%3E3.0.co;2-o
JOHANSSON, I.M.; BIRZNIECE, V.; LINDBLAD, C.; OLSSON, T.; BÄCKSTRÖM, T. Allopregnanolone Inhibits Learning in the Morris Water Maze. Brain Research, v. 934, n. 2, p. 125-131, 2002. https://doi.org/10.1016/s0006-8993(02)02414-9
KASK, K.; GULINELLO, M.; BÄCKSTRÖM, T.; GEYER, M.A.; SUNDSTRÖM-POROMAA, I. Patients with Premenstrual Dysphoric Disorder Have Increased Startle Response Across Both Cycle Phases and Lower Levels of Prepulse Inhibition During the Late Luteal Phase of the Menstrual Cycle. Neuropsychopharmacology, v. 33, n. 9, p. 2283-2290, 2008. https://doi.org/10.1038/sj.npp.1301599
KAUR, G.; GONSALVES, L.; THACKER, H.L. Premenstrual Dysphoric Disorder: a Review for the Treating Practitioner. Cleveland Clinic Journal of Medicine, v. 71, n. 4, p. 303-305, 2004. https://doi.org/10.3949/ccjm.71.4.303
LANDGREN, S.; SELSTAM, G. Interaction Between 17-beta-oestradiol and 3-alpha-hydroxy-5-alpha-pregnane-20-one in the Control of Neuronal Excitability in Slices from The CA1 Hippocampus In Vitro of Guinea-pigs and Rats. Acta Physiologica, v. 154, n. 2, p. 165-176, 1995. https://doi.org/10.1111/j.1748-1716.1995.tb09898.x
MAJEWSKA, M. D.; HARRISON, N. L.; SCHWARTZ, R. D.; BARKER, J. L.; PAUL, S. M. Steroid Hormone Metabolites Are Barbiturate-Like Modulators of the GABA Receptor. Science, v. 234, n. 4753, p. 1004-1007, 1986. https://doi.org/10.1126/science.2422758
MCCORMICK, D. A. GABA as an Inhibitory Neurotransmitter in Human Cerebral Cortex. Journal of Neurophysiology, v. 62, n. 5, p. 1018-1027, 1989. https://doi.org/10.1152/jn.1989.62.5.1018
MICZEK, K.A.; WEERTS, E.M.; DEBOLD, J.F. Alcohol, Benzodiazepine-GABAA Receptor Complex and Aggression: Ethological Analysis of Individual Differences in Rodents and Primates. Journal of Studies on Alcohol, v.11, n.11, p. 170-179, 1993. http://dx.doi.org/10.15288/jsas.1993.s11.170
NYBERG, S.; WAHLSTRÖM, G.; BÄCKSTRÖM, T.; SUNDSTRÖM-POROMAA, I. Altered Sensitivity to Alcohol in the Late Luteal Phase Among Patients with Premenstrual Dysphoric Disorder. Psychoneuroendocrinology, v. 29, n. 6, p. 767-777, 2004. https://doi.org/10.1016/S0306-4530(03)00121-5
SANACORA, G.; MASON, G.F.; ROTHMAN, D.L.; BEHAR, K.L.; HYDER, F.; PETROFF, O.A.C.; BERMAN, R.M.; CHARNEY, D.S.; KRYSTAL, J.H. Reduced Cortical Gamma-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy. Archives of General Psychiatry, v. 56, n. 11, p.1043-1047, 1999. https://doi.org/10.1001/archpsyc.56.11.1043
SCHMIDT, P.J.; NIEMAN, L.K.; DANACEAU, M.A.; ADAMS, L.F.; RUBINOW, D.R. Differential Behavioral Effects of Gonadal Steroids in Women With and in Those Without Premenstrual Syndrome. The New England Journal of Medicine, v. 338, n. 4, p. 209-216, 1998. https://doi.org/10.1056/NEJM199801223380401
SEGEBLADH, B.; BORGSTRÖM, A.; NYBERG, S.; BIXO, M.; SUNDSTRÖM-POROMAA, I. Evaluation of Different Add-back Estradiol and Progesterone Treatments to Gonadotropin-releasing Hormone Agonist Treatment in Patients with Premenstrual Dysphoric Disorder. American Journal of Obstetrics and Gynecology, v. 201, n. 2, p. 139.e1-139.e8, 2009. https://doi.org/10.1016/j.ajog.2009.03.016
SHAH, N.R.; JONES, J.B.; APERI, J.; SHEMTOV, R.; KARNE, A.; BORENSTEIN, J. Selective Serotonin Reuptake Inhibitors for Premenstrual Syndrome and Premenstrual Dysphoric Disorder: a Meta-analysis. Obstetrics and Gynecology, v. 111, n. 5, p. 1175-1182, 2008. https://doi.org/10.1097/AOG.0b013e31816fd73b
SIEGHART, W. Structure and Pharmacology of y-Aminobutyric AcidA Receptor Subtypes. Pharmacological Reviews, v. 46, n. 2, 181-234, 1995.
SMILEY, J.F.; GOLDMAN-RAKIC, P.S. Serotonergic Axons in Monkey Prefrontal Cerebral Cortex Synapse Predominantly on Interneurons as Demonstrated by Serial Section Electron Microscopy. The Journal of Comparative Neurology, v. 367, n. 3, p. 431-443, 1996. https://doi.org/10.1002/(SICI)1096-9861(19960408)367:3%3C431::AID-CNE8%3E3.0.CO;2-6
SUNDSTRÖM, I.; ANDERSSON, A.; NYBERG, S.; ASHBROOK, D.; PURDY, R.H.; BÄCKSTRÖM, T. Patients with Premenstrual Syndrome Have a Different Sensitivity to a Neuroactive Steroid During the Menstrual Cycle Compared to Control Subjects. Neuroendocrinology, v. 67, n.2, p. 126-138, 1998. https://doi.org/10.1159/000054307
SUNDSTRÖM, I.; NYBERG, S.; BÄCKSTRÖM, T. Patients with Premenstrual Syndrome Have Reduced Sensitivity to Midazolam Compared to Control Subjects. Neuropsychopharmacology, v. 17, n. 6, p. 370-381, 1997. https://doi.org/10.1016/S0893-133X(97)00086-9
SUNDSTRÖM-POROMAA, I.; SMITH, S.; GULINELLO, M. GABA Receptors, Progesterone and Premenstrual Dysphoric Disorder. Archives of Women’s Mental Health, v. 6, n. 1, p. 23-41, 2003. https://doi.org/10.1007/s00737-002-0147-1
VALADARES, G.C.; FERREIRA, L.V.; CORREA FILHO, H.; ROMANO-SILVA, M.C. Transtorno disfórico pré-menstrual revisão – conceito, história, epidemiologia e etiologia. Revista de Psiquiatria Clínica, v. 33, n. 3, p. 117-123, 2006. http://dx.doi.org/10.1590/S0101-60832006000300001
WANG, M.; SEIPPEL, L.; PURDY, R.H.; BÄCKSTRÖM, T. Relationship Between Symptom Severity and Steroid Variation in Women with Premenstrual Syndrome: Study on Serum Pregnenolone, Pregnenolone Sulfate, 5-alpha-pregnane-3,20-dione and 3-alpha-hydroxy-5-alpha-pregnan-20-one. Journal of Clinical Endocrinology and Metabolism, v. 81, n. 3, p. 1076-1082, 1996. https://doi.org/10.1210/jcem.81.3.8772579
WENZEL, R.R.; BARTEL, T.; EGGEBRECHT, H.; PHILIPP, T.; ERBEL, R. Central-nervous Side Effects of Midazolam During Transesophageal Echocardiography. Journal of the American Society of Echocardiography, v. 15, n. 10 (pt. 2), p. 1297-1300, 2002. https://doi.org/10.1067/mje.2002.124572
YOSHIMURA, H.; OGAWA, N. Acute and Chronic Effects of Psychotropic Drugs on Maternal Aggression in Mice. Psychopharmacology (Berl), v. 97, n. 3, p. 339-342, 1989. https://doi.org/10.1007/bf00439447
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