Skip to main content
Erschienen in: Archives of Women's Mental Health 2/2020

21.03.2019 | Original Article

Improvement in depression with oestrogen treatment in women with schizophrenia

verfasst von: M. Bové Lascurain, A. Camuñas-Palacín, N. Thomas, C. Breadon, E. Gavrilidis, A. R. Hudaib, C. Gurvich, J. Kulkarni

Erschienen in: Archives of Women's Mental Health | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

Women with schizophrenia are often noted to suffer with comorbid depression. Many studies have shown associations between fluctuating oestrogen levels in the brain and mental illness. This study investigates the effect of oestradiol treatment on comorbid depressive symptoms in women with schizophrenia. This study is an 8-week, three-arm, double-blind, randomised-controlled trial. The 180 female participants were aged between 18 and 45, with schizophrenia and ongoing symptoms of psychosis Positive and Negative Syndrome Scale (PANSS) score > 60 despite a stable dose of antipsychotic medication. Depressive symptoms were assessed using Montgomery Asberg Depression Scale (MADRS) with a mean score of 73.77 at baseline. Participants received transdermal oestradiol 200 μg or transdermal oestradiol 100 μg or an identical placebo patch. The a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56, but in this study, we focused on the change in MADRS score at the same time points. Data were analysed by using Quade’s rank analysis of covariance (ANCOVA) (Huitema 1980) with baseline MADRS score as a covariate. We found a fluctuating but overall trend towards improvement of comorbid depressive symptoms in women with schizophrenia taking transdermal oestrogen 200 mcg compared with oestrogen 100 mcg or placebo. The stronger ‘antidepressant’ effect of 200 mcg transdermal oestradiol was found at day 28 (p = 0.03). Our study suggests that adjunctive oestradiol treatment for depression may be a promising treatment for women with comorbid depression and schizophrenia.
Literatur
Zurück zum Zitat Amsterdam J, Garcia-España F, Fawcett J, Quitkin F, Reimherr F, Rosenbaum J, Beasley C (1999) Fluoxetine efficacy in menopausal women with and without estrogen replacement. J Affect Disord 55(1):11–17CrossRef Amsterdam J, Garcia-España F, Fawcett J, Quitkin F, Reimherr F, Rosenbaum J, Beasley C (1999) Fluoxetine efficacy in menopausal women with and without estrogen replacement. J Affect Disord 55(1):11–17CrossRef
Zurück zum Zitat Behl C (2002) Estrogen can protect neurons: modes of action. J Steroid Biochem Mol Biol 83:195–197CrossRef Behl C (2002) Estrogen can protect neurons: modes of action. J Steroid Biochem Mol Biol 83:195–197CrossRef
Zurück zum Zitat Behl C, Manthey D (2000) Neuroprotective activities of estrogen: an update. J Neurocytol 29:351–358CrossRef Behl C, Manthey D (2000) Neuroprotective activities of estrogen: an update. J Neurocytol 29:351–358CrossRef
Zurück zum Zitat Benmansour S, Adeniji OS, Privratsky AA, Frazer A (2015) Effects of long-term treatment with estradiol and estrogen receptor subtype agonists on serotonergic function in Ovariectomized rats. Neuroendocrinology 103(3–4):269–281PubMedPubMedCentral Benmansour S, Adeniji OS, Privratsky AA, Frazer A (2015) Effects of long-term treatment with estradiol and estrogen receptor subtype agonists on serotonergic function in Ovariectomized rats. Neuroendocrinology 103(3–4):269–281PubMedPubMedCentral
Zurück zum Zitat Birzniece V, Johansson IM, Wang MD, Seckl JR, Backstrom T, Olsson T (2001) Serotonin 5-HT(1A) receptor mRNA expression in dorsal hippocampus and raphe nuclei after gonadal hormone manipulation in female rats. Neuroendocrinology 74:135–142CrossRef Birzniece V, Johansson IM, Wang MD, Seckl JR, Backstrom T, Olsson T (2001) Serotonin 5-HT(1A) receptor mRNA expression in dorsal hippocampus and raphe nuclei after gonadal hormone manipulation in female rats. Neuroendocrinology 74:135–142CrossRef
Zurück zum Zitat Borrow A et al (2014) Estrogenic mediation of serotonergic and neurotropic systems: implications for female mood disorders. Prog Neuro-Psychopharmacol Biol Psychiatry 54:13–25CrossRef Borrow A et al (2014) Estrogenic mediation of serotonergic and neurotropic systems: implications for female mood disorders. Prog Neuro-Psychopharmacol Biol Psychiatry 54:13–25CrossRef
Zurück zum Zitat Buckley B et al (2009) Psychiatric comorbidities and schizophrenia. Schizophr Bull 35(2):383–402CrossRef Buckley B et al (2009) Psychiatric comorbidities and schizophrenia. Schizophr Bull 35(2):383–402CrossRef
Zurück zum Zitat Claudio N et al (2008) Reproductive hormone sensitivity and risk for depression across the female life cycle: a continuum of vulnerability? J Psychiatry Neurosci 33(4):331–343 Claudio N et al (2008) Reproductive hormone sensitivity and risk for depression across the female life cycle: a continuum of vulnerability? J Psychiatry Neurosci 33(4):331–343
Zurück zum Zitat Garcia-Segura LM, Azcoitia I, DonCarlos LL (2001) Neuroprotection by estradiol. Prog Neurobiol 63:29–60CrossRef Garcia-Segura LM, Azcoitia I, DonCarlos LL (2001) Neuroprotection by estradiol. Prog Neurobiol 63:29–60CrossRef
Zurück zum Zitat Häfner H, Behrens S, de Vry J, Gattaz WF (1991) An animal model for the effects of estradiol on dopamine-mediated behavior: implications for sex differences in schizophrenia. Psychiatry Res 38(2):125–134CrossRef Häfner H, Behrens S, de Vry J, Gattaz WF (1991) An animal model for the effects of estradiol on dopamine-mediated behavior: implications for sex differences in schizophrenia. Psychiatry Res 38(2):125–134CrossRef
Zurück zum Zitat Robert M. Julien (2010) A primer drug action: a comprehensive guide to the actions, uses, and side effects of psychoactive drugs 12th edition Robert M. Julien (2010) A primer drug action: a comprehensive guide to the actions, uses, and side effects of psychoactive drugs 12th edition
Zurück zum Zitat Kleeblatt J, Betzler F, Kilarski LL, Bschor T, Köhler S (2017) Efficacy of off-label augmentation in unipolar depression: a systematic review of the evidence. Eur Neuropsychopharmacol 27(5):423–441CrossRef Kleeblatt J, Betzler F, Kilarski LL, Bschor T, Köhler S (2017) Efficacy of off-label augmentation in unipolar depression: a systematic review of the evidence. Eur Neuropsychopharmacol 27(5):423–441CrossRef
Zurück zum Zitat Kulkarni J, Gavrilidis E, Naughton B, Worsley R, Gurvich C, Lee S, de Castella A, Fitzgerald P (2002) Estrogen—a new treatment for schizoaffective disorder. Biol Psychiatry Australia Kulkarni J, Gavrilidis E, Naughton B, Worsley R, Gurvich C, Lee S, de Castella A, Fitzgerald P (2002) Estrogen—a new treatment for schizoaffective disorder. Biol Psychiatry Australia
Zurück zum Zitat Kulkarni J, Gurvich C, Gilbert H, Mehmedbegovic F, Mu L, Marston N, Gavrilidis E, de Castella A (2008a) Hormone modulation: a novel therapeutic approach for women with severe mental illness. Aust N Z J Psychiatry 42(1):83–88CrossRef Kulkarni J, Gurvich C, Gilbert H, Mehmedbegovic F, Mu L, Marston N, Gavrilidis E, de Castella A (2008a) Hormone modulation: a novel therapeutic approach for women with severe mental illness. Aust N Z J Psychiatry 42(1):83–88CrossRef
Zurück zum Zitat Kulkarni J, de Castella A, Fitzgerald PB, Gurvich CT, Bailey M, Bartholomeusz C, Burger H (2008b) Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry 65(8):955–960CrossRef Kulkarni J, de Castella A, Fitzgerald PB, Gurvich CT, Bailey M, Bartholomeusz C, Burger H (2008b) Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry 65(8):955–960CrossRef
Zurück zum Zitat Le Saux M, Morissette M, Di Paolo T (2006) ERβ mediates the estradiol increase of D 2 receptors in rat striatum and nucleus accumbens. Neuropharmacology 50(4):451–457CrossRef Le Saux M, Morissette M, Di Paolo T (2006) ERβ mediates the estradiol increase of D 2 receptors in rat striatum and nucleus accumbens. Neuropharmacology 50(4):451–457CrossRef
Zurück zum Zitat Lemini C, Cruz-López B, Martínez-Mota L (2013) Participation of estrogen receptors in the antidepressant-like effect of prolame on the forced swimming test. Pharmacol Biochem Behav 103(3):659–665CrossRef Lemini C, Cruz-López B, Martínez-Mota L (2013) Participation of estrogen receptors in the antidepressant-like effect of prolame on the forced swimming test. Pharmacol Biochem Behav 103(3):659–665CrossRef
Zurück zum Zitat Lindamer LA, Lohr JB, Harris MJ, Jeste DV (1997) Gender, estrogen, and schizophrenia. Psychopharmacol Bull 33(2):221–228PubMed Lindamer LA, Lohr JB, Harris MJ, Jeste DV (1997) Gender, estrogen, and schizophrenia. Psychopharmacol Bull 33(2):221–228PubMed
Zurück zum Zitat McEwen BS (2001) Estrogens effects on the brain: multiple sites and molecular mechanisms. J Appl Physiol 91:2785–2801CrossRef McEwen BS (2001) Estrogens effects on the brain: multiple sites and molecular mechanisms. J Appl Physiol 91:2785–2801CrossRef
Zurück zum Zitat Meitzen J, Mermelstein PG (2011) Estrogen receptors stimulate brain region specific metabotropic glutamate receptors to rapidly initiate signal transduction pathways. J Chem Neuroanat 42(4):236–241CrossRef Meitzen J, Mermelstein PG (2011) Estrogen receptors stimulate brain region specific metabotropic glutamate receptors to rapidly initiate signal transduction pathways. J Chem Neuroanat 42(4):236–241CrossRef
Zurück zum Zitat Mendrek A, Mancini-Marïe A (2016) Sex/gender differences in the brain and cognition in schizophrenia. Neurosci Biobehav Rev 67:57–78CrossRef Mendrek A, Mancini-Marïe A (2016) Sex/gender differences in the brain and cognition in schizophrenia. Neurosci Biobehav Rev 67:57–78CrossRef
Zurück zum Zitat Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134(4):382–389CrossRef Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134(4):382–389CrossRef
Zurück zum Zitat Österlund MK (2010) Underlying mechanisms mediating the antidepressant effects of estrogens. Biochimica et Biophysica Acta (BBA)-General Subjects 1800(10):1136–1144CrossRef Österlund MK (2010) Underlying mechanisms mediating the antidepressant effects of estrogens. Biochimica et Biophysica Acta (BBA)-General Subjects 1800(10):1136–1144CrossRef
Zurück zum Zitat Riecher-Rössler A et al (1994) Can estradiol modulate schizophrenic symptomatology? Schizophr Bull 20(1):203–214CrossRef Riecher-Rössler A et al (1994) Can estradiol modulate schizophrenic symptomatology? Schizophr Bull 20(1):203–214CrossRef
Zurück zum Zitat Saha S et al (2005) A systematic review of the prevalence of schizophrenia. PLoS Med 2(5):413CrossRef Saha S et al (2005) A systematic review of the prevalence of schizophrenia. PLoS Med 2(5):413CrossRef
Zurück zum Zitat Schiller C et al (2016) Reproductive steroid regulation of mood and behaviour. Compr Physiol 6(3):1135–1160CrossRef Schiller C et al (2016) Reproductive steroid regulation of mood and behaviour. Compr Physiol 6(3):1135–1160CrossRef
Zurück zum Zitat Schneider LS, Small GW, Hamilton SH, Bystritsky A, Nemeroff CB, Meyers BS (1997) Estrogen replacement and response to fluoxetine in a multicenter geriatric depression trial. Am J Geriatr Psychiatry 5(2):97–106CrossRef Schneider LS, Small GW, Hamilton SH, Bystritsky A, Nemeroff CB, Meyers BS (1997) Estrogen replacement and response to fluoxetine in a multicenter geriatric depression trial. Am J Geriatr Psychiatry 5(2):97–106CrossRef
Zurück zum Zitat Schneider LS, Small GW, Clary CM (2001) Estrogen replacement therapy and antidepressant response to sertraline in older depressed women. Am J Geriatr Psychiatry 9(4):393–399CrossRef Schneider LS, Small GW, Clary CM (2001) Estrogen replacement therapy and antidepressant response to sertraline in older depressed women. Am J Geriatr Psychiatry 9(4):393–399CrossRef
Zurück zum Zitat Seeman MV (1986) Current outcome in schizophrenia: women vs men. Acta Psychiatr Scand 73(6):609–617CrossRef Seeman MV (1986) Current outcome in schizophrenia: women vs men. Acta Psychiatr Scand 73(6):609–617CrossRef
Zurück zum Zitat Seeman MV, Lang M (1990) The role of estrogens in schizophrenia gender differences. Schizophr Bull 16(2):185–194CrossRef Seeman MV, Lang M (1990) The role of estrogens in schizophrenia gender differences. Schizophr Bull 16(2):185–194CrossRef
Zurück zum Zitat Shapira B, Oppenheim G, Zohar J, Segal M, Malach D, Belmaker RH (1985) Lack of efficacy of estrogen supplementation to imipramine in resistant female depressives. Biol Psychiatry 20(5):576–579CrossRef Shapira B, Oppenheim G, Zohar J, Segal M, Malach D, Belmaker RH (1985) Lack of efficacy of estrogen supplementation to imipramine in resistant female depressives. Biol Psychiatry 20(5):576–579CrossRef
Zurück zum Zitat Shimamoto A, Rappeneau V (2017) Sex-dependent mental illnesses and mitochondria. Schizophr Res 187:38–46CrossRef Shimamoto A, Rappeneau V (2017) Sex-dependent mental illnesses and mitochondria. Schizophr Res 187:38–46CrossRef
Zurück zum Zitat Simpson G, Angus J (1970) A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 45(S212):11–19CrossRef Simpson G, Angus J (1970) A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 45(S212):11–19CrossRef
Zurück zum Zitat Siris SG (2000) Depression in schizophrenia: perspective in the era of “atypical” antipsychotic agents. Am J Psychiatr 157:1379–1389CrossRef Siris SG (2000) Depression in schizophrenia: perspective in the era of “atypical” antipsychotic agents. Am J Psychiatr 157:1379–1389CrossRef
Zurück zum Zitat Soares CN, Almeida OP, Joffe H, Cohen LS (2001) Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 58(6):529–534CrossRef Soares CN, Almeida OP, Joffe H, Cohen LS (2001) Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 58(6):529–534CrossRef
Zurück zum Zitat Sumner BEH et al (2007) Hormones; research on hormones described by B.E.H. Sumner and colleagues. Health and medicine week p.4468 ISSN: 1531-6459 Sumner BEH et al (2007) Hormones; research on hormones described by B.E.H. Sumner and colleagues. Health and medicine week p.4468 ISSN: 1531-6459
Zurück zum Zitat Tam LW, Parry BL (2003) Does estrogen enhance the antidepressant effects of fluoxetine? J Affect Disord 77(1):87–92CrossRef Tam LW, Parry BL (2003) Does estrogen enhance the antidepressant effects of fluoxetine? J Affect Disord 77(1):87–92CrossRef
Zurück zum Zitat Thase ME, Entsuah R, Cantillon M, Kornstein SG (2005) Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Women's Health 14(7):609–616CrossRef Thase ME, Entsuah R, Cantillon M, Kornstein SG (2005) Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Women's Health 14(7):609–616CrossRef
Zurück zum Zitat Vega-Rivera N, López-Rubalcava C, Estrada-Camarena E (2013) the antidepressant-like effect of ethynyl estradiol is mediated by both serotonergic and noradrenergic systems in the forced swimming test. Neuroscience 250:102–111CrossRef Vega-Rivera N, López-Rubalcava C, Estrada-Camarena E (2013) the antidepressant-like effect of ethynyl estradiol is mediated by both serotonergic and noradrenergic systems in the forced swimming test. Neuroscience 250:102–111CrossRef
Metadaten
Titel
Improvement in depression with oestrogen treatment in women with schizophrenia
verfasst von
M. Bové Lascurain
A. Camuñas-Palacín
N. Thomas
C. Breadon
E. Gavrilidis
A. R. Hudaib
C. Gurvich
J. Kulkarni
Publikationsdatum
21.03.2019
Verlag
Springer Vienna
Erschienen in
Archives of Women's Mental Health / Ausgabe 2/2020
Print ISSN: 1434-1816
Elektronische ISSN: 1435-1102
DOI
https://doi.org/10.1007/s00737-019-00959-3

Weitere Artikel der Ausgabe 2/2020

Archives of Women's Mental Health 2/2020 Zur Ausgabe

Neu in den Fachgebieten Neurologie und Psychiatrie