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      Reproductive hormonal treatments for mood disorders in women Translated title: Tratamientos con hormonas de la reproducción para los trastornos del ánimo en las mujeres Translated title: Traitements hormonaux de la fonction reproductrice utilisés pour les troubles de l'humeur chez la femme

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          Abstract

          There has been a century-long view in medicine that reproductive function in both men and women is intimately involved with mood regulation. The 19th century witnessed a proliferation of medical reports documenting beneficial effects on mood and behavior after medical or surgical manipulations of women's reproductive functíon. More recently, the results of several studies suggest that gonadal steroids do regulate mood in some women. Thus, there is considerable interest in the potential role of reproductive therapies in the management of depressive illness, including both classical and reproductive endocrine-related mood disorders. Future studies need to determine the predictors of response to hormonal therapies compared with traditional antidepressant agents, and to characterize the long-term safety and benefits of these therapies.

          Translated abstract

          Desde hace más de un siglo en la medícina ha existido la visión que la función reproductora tanto en los hombres como en las mujeres está íntimamente relacionada con la regulación del ánimo. El siglo XIX fue testigo de una proliferación de informes médicos en que se documentaban los beneficios sobre el ánimo y la conducta luego de manipular médica o quirúrgicamente la función reproductora de las mujeres. Más recientemente, los resultados de diversos estudios sugieren que los esteroides gonadales regulan el ánimo en algunas mujeres. Es así como existe un considerable interés en el potencial papel de las terapias con hormonas de la reproducción en el manejo de la enfermedad depresiva, incluyendo tanto los trastornos del ánimo clásicos como aquéllos relacionados con la endocrinología de la reproducción. Se requiere de futuros estudios para determinar predictores de respuesta a terapias hormonales comparadas con agentes antidepresivos tradicionales y también para caracterizar la seguridad a largo plazo y los beneficios de estas terapias.

          Translated abstract

          Depuis plus d'un siècle, la médecine a pensé que la fonction reproductrice, aussi bien chez l'homme que chez la femme, était intimement liée avec la régulation de l'humeur. Le XIX e siècle fut le témoin d'une pléthore de textes affirmant les effets bénéfiques sur l'humeur et le comportement de manipulations médicales ou chirurgicales de la fonction reproductrice féminine. Plus récemment, les résultats de plusieurs études ont suggéré que les stéroïdes gonadiques régulaient l'humeur de certaines femmes. Le rôle potentiel des traitements de la fonction reproductrice présente ainsi un intérêt considérable dans la prise en charge de la maladie dépressive, tant sur le plan des troubles de l'humeur classiques que de ceux liés à l'endocrinologie de la reproduction. Les études à venir devront déterminer les facteurs prédictifs des réponses aux thérapies hormonales comparés aux traitements antidépresseurs classiques et définir la tolérance à long terme et les bénéfices de ces traitements.

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          A molecular and cellular theory of depression.

          Recent studies have begun to characterize the actions of stress and antidepressant treatments beyond the neurotransmitter and receptor level. This work has demonstrated that long-term antidepressant treatments result in the sustained activation of the cyclic adenosine 3',5'-monophosphate system in specific brain regions, including the increased function and expression of the transcription factor cyclic adenosine monophosphate response element-binding protein. The activated cyclic adenosine 3',5'-monophosphate system leads to the regulation of specific target genes, including the increased expression of brain-derived neurotrophic factor in certain populations of neurons in the hippocampus and cerebral cortex. The importance of these changes is highlighted by the discovery that stress can decrease the expression of brain-derived neurotrophic factor and lead to atrophy of these same populations of stress-vulnerable hippocampal neurons. The possibility that the decreased size and impaired function of these neurons may be involved in depression is supported by recent clinical imaging studies, which demonstrate a decreased volume of certain brain structures. These findings constitute the framework for an updated molecular and cellular hypothesis of depression, which posits that stress-induced vulnerability and the therapeutic action of antidepressant treatments occur via intracellular mechanisms that decrease or increase, respectively, neurotrophic factors necessary for the survival and function of particular neurons. This hypothesis also explains how stress and other types of neuronal insult can lead to depression in vulnerable individuals and it outlines novel targets for the rational design of fundamentally new therapeutic agents.
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            Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.

            The present study demonstrates that chronic, but not acute, adminstration of several different classes of antidepressants, including serotonin- and norepinephrine-selective reuptake inhibitors, increases the expression of cAMP response element binding protein (CREB) mRNA in rat hippocampus. In contrast, chronic administration of several nonantidepressant psychotropic drugs did not influence expression of CREB mRNA, demonstrating the pharmacological specificity of this effect. In situ hybridization analysis demonstrates that antidepressant administration increases expression of CREB mRNA in CA1 and CA3 pyramidal and dentate gyrus granule cell layers of the hippocampus. In addition, levels of CRE immunoreactivity and of CRE binding activity were increased by chronic antidepressant administration, which indicates that expression and function of CREB protein are increased along with its mRNA. Chronic administration of the phosphodiesterase (PDE) inhibitors rolipram or papaverine also increased expression of CREB mRNA in hippocampus, demonstrating a role for the cAMP cascade. Moreover, coadministration of rolipram with imipramine resulted in a more rapid induction of CREB than with either treatment alone. Increased expression and function of CREB suggest that specific target genes may be regulated by these treatments. We have found that levels of brain-derived neurotrophic factor (BDNF) and trkB mRNA are also increased by administration of antidepressants or PDE inhibitors. These findings indicate that upregulation of CREB is a common action of chronic antidepressant treatments that may lead to regulation of specific target genes, such as BDNF and trkB, and to the long-term effects of these treatments on brain function.
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              Universities and tobacco money.

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                Author and article information

                Contributors
                Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, Md, USA
                Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, Md, USA
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                June 2002
                June 2002
                : 4
                : 2
                : 211-223
                Affiliations
                Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, Md, USA
                Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, Md, USA
                Author notes
                Article
                3181679
                22033644
                6d3a03a7-1f78-4dac-a4d4-51898b9e89bf
                Copyright: © 2002 LLS

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Clinical Research

                Neurosciences
                depression,progesterone,women,dhea,antidepressants,estrogen
                Neurosciences
                depression, progesterone, women, dhea, antidepressants, estrogen

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