Orientador: Silvio Yasui / Co-orientador: Gustavo Henrique Dionísio / Banca: Charles Dalcanale Tesser / Banca: Mary Yoko Okamoto / Resumo: Não é de hoje que a humanidade busca remédios para atenuar, tratar e curar os mais diferentes tipos de sofrimento. Com as "doenças da alma/corpo" a história não tem sido diferente. Pesquisamos os efeitos do uso a longo prazo de antidepressivos a partir do relato de cinco pessoas, que utilizam o remédio há mais de três anos. O estado subjetivo da depressão e os antidepressivos são as contingências que fornecem os relevos para respondermos sobre a existência de um sofrimento remanescente ao uso do psicofármaco. Deste modo, na pesquisa investigamos como a medicalização da depressão entra num dispositivo que faz dela a realidade do tratamento dos transtornos psíquicos, o contexto no qual a depressão se insere e a sua função no intercâmbio social. Desdobramos as múltiplas faces dos psicofármacos, resgatando, o conflito inerente ao phármakon. A prescrição do phármakon no tratamento em saúde mental traz a necessidade do debater da dimensão ética, pois ao mesmo tempo em que os psicofármacos podem ser aliados importantes, não devem retirar o protagonismo do sujeito no seu tratamento. Sendo assim, revisitamos e procuramos realocar o discurso d@s entrevistad@s como elemento essencial para a análise. As entrevistas relatam vivências que nos mostram que o estado depressivo é, antes de tudo, uma experiência sensível e não é apenas consequência de um déficit neuroquímico, passível de ser corrigido com antidepressivos. Os relatos guardam histórias de diversos tipos de violência, tentativas de suicídio com uso de psicofármacos, internações hospitalares etc. Trata-se de histórias que foram escamoteadas no processo de medicalização. Deste modo, amparados na psicanálise, posicionamo-nos a partir da ética do bem-dizer, tendo como prerrogativa que o antidepressivo não pode tamponar a palavra do sujeito em sofrimento psíquico. Sabemos, por meio de Freud/Lacan, que a ... / Abstract: It is not from today that humanity seeks medicines to mitigate, treat and cure the most different kinds of suffering. With the "diseases of the soul/body" the story has been no different. We researched the effects of long term use of antidepressives from the report of five people who use the drug for more than three years. The subjective state of depression and antidepressives are the contingencies that provide reliefs to answer on the existence of a remnant suffering to the use of psychotropic. Thereby, the research investigated how the medicalization of depression enters a device which makes it the reality of the treatment of mental disorders, the context in which depression is part and its function in social exchange. We have deployed the multiple facets of psychotropics, rescuing the conflict inherent in the phármakon. The limitation of phármakon in mental health treatment brings the need to discuss the ethical dimension, because while that drugs can be important allies, they should not take the role of the subject in its treatment. So, we revisit and try to relocate the discourse of the interviewed as an essential element for the analysis. The interviews reported experiences that show us that the depressive state is above all a sense experience and not just a consequence of that can be corrected with antidepressants neurochemical deficit. The reports keep stories of various types violence, suicide attempts with the use of psychotropic drugs, hospitalizations etc. Stories that were concealed in the medicalization process. So we set ourselves from the ethics of psychoanalysis, whose prerogative that antidepressives cannot buffer the word of the subject in psychological distress. We know through of Freud/Lacan, that symptomatic complaint is just the beginning of treatment and that the work takes from it. We conclude that the antidepressives after long-term use can make it difficult to appropriate ... / Mestre

Made available in DSpace on 2014-11-10T11:09:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-01-22Bitstream added on 2014-11-10T11:57:28Z : No. of bitstreams: 1 000780309.pdf: 1083444 bytes, checksum: dce52b020887fcab16c85ebe6baa8741 (MD5) / Não é de hoje que a humanidade busca remédios para atenuar, tratar e curar os mais diferentes tipos de sofrimento. Com as ”doenças da alma/corpo” a história não tem sido diferente. Pesquisamos os efeitos do uso a longo prazo de antidepressivos a partir do relato de cinco pessoas, que utilizam o remédio há mais de três anos. O estado subjetivo da depressão e os antidepressivos são as contingências que fornecem os relevos para respondermos sobre a existência de um sofrimento remanescente ao uso do psicofármaco. Deste modo, na pesquisa investigamos como a medicalização da depressão entra num dispositivo que faz dela a realidade do tratamento dos transtornos psíquicos, o contexto no qual a depressão se insere e a sua função no intercâmbio social. Desdobramos as múltiplas faces dos psicofármacos, resgatando, o conflito inerente ao phármakon. A prescrição do phármakon no tratamento em saúde mental traz a necessidade do debater da dimensão ética, pois ao mesmo tempo em que os psicofármacos podem ser aliados importantes, não devem retirar o protagonismo do sujeito no seu tratamento. Sendo assim, revisitamos e procuramos realocar o discurso d@s entrevistad@s como elemento essencial para a análise. As entrevistas relatam vivências que nos mostram que o estado depressivo é, antes de tudo, uma experiência sensível e não é apenas consequência de um déficit neuroquímico, passível de ser corrigido com antidepressivos. Os relatos guardam histórias de diversos tipos de violência, tentativas de suicídio com uso de psicofármacos, internações hospitalares etc. Trata-se de histórias que foram escamoteadas no processo de medicalização. Deste modo, amparados na psicanálise, posicionamo-nos a partir da ética do bem-dizer, tendo como prerrogativa que o antidepressivo não pode tamponar a palavra do sujeito em sofrimento psíquico. Sabemos, por meio de Freud/Lacan, que a ... / It is not from today that humanity seeks medicines to mitigate, treat and cure the most different kinds of suffering. With the diseases of the soul/body the story has been no different. We researched the effects of long term use of antidepressives from the report of five people who use the drug for more than three years. The subjective state of depression and antidepressives are the contingencies that provide reliefs to answer on the existence of a remnant suffering to the use of psychotropic. Thereby, the research investigated how the medicalization of depression enters a device which makes it the reality of the treatment of mental disorders, the context in which depression is part and its function in social exchange. We have deployed the multiple facets of psychotropics, rescuing the conflict inherent in the phármakon. The limitation of phármakon in mental health treatment brings the need to discuss the ethical dimension, because while that drugs can be important allies, they should not take the role of the subject in its treatment. So, we revisit and try to relocate the discourse of the interviewed as an essential element for the analysis. The interviews reported experiences that show us that the depressive state is above all a sense experience and not just a consequence of that can be corrected with antidepressants neurochemical deficit. The reports keep stories of various types violence, suicide attempts with the use of psychotropic drugs, hospitalizations etc. Stories that were concealed in the medicalization process. So we set ourselves from the ethics of psychoanalysis, whose prerogative that antidepressives cannot buffer the word of the subject in psychological distress. We know through of Freud/Lacan, that symptomatic complaint is just the beginning of treatment and that the work takes from it. We conclude that the antidepressives after long-term use can make it difficult to appropriate ...

Serotonin gilt als Hauptangriffsstelle gängiger Antidepressiva bei schweren Depressionen, wie bspw. selektive Serotonin-Wiederaufnahmehemmer (SSRI), und -Enhancer (SSRE). Es bleibt offen, ob SSRI / E ausschließlich über die Manipulation des Serotoninspiegels wirken, oder ob alternative Signalwege daran beteiligt sind. Ansatzpunkte hierfür sind beispielsweise die neurotrophen Signalwege (spez. Brain derived neurotophic factor, BDNF) oder die Hypothalamus-Hypophysen-Nebennieren- (HPA) – Signalwege des Stressachsensystems. Ebenfalls wurde in Nagetiermodellen beobachtet, dass mit der Dysregulation des zentralen Serotoninsystems bei schweren Depressionen, ein Rückgang der Neurogenese im Gyrus dentatus des Hippocampus einhergeht. Ziel dieser Arbeit war, das Zusammenspiel von Serotonin, BDNF, adulter Neurogenese und der Stressachse zu untersuchen. Zentrum der Studien ist ein Mausmodell, mit einer genetischen Depletion des zentralen Serotonin-synthetisierenden Enzyms Tryptophanhydroxylase 2 (sog. Tph2-/- Mäuse). Es wurden die physiologische Reaktionen auf die Behandlung mit gängigen Antidepressiva abhängig von der Abwesenheit von Serotonin untersucht, um mögliche alternative Signalwege aufzeigen zu können. Die bekannte Zunahme der Neurogenese nach SSRI/SSRE-Behandlung wurde in Wildtyptieren beobachtet, während die Therapie in Tph2-/- Mäusen keine direkte kausale Wirkung zeigte. Im Gegensatz dazu waren die BDNF-Spiegel in depressionsrelevanten Hirnregionen in Tph2-/- Mäusen nach SSRI, signifikant verringert. Auch zeigen die Studien eine neurobiologische Relevanz von Serotonin im ZNS, bei den antidepressiven Mechanismen einer Elektrokonvulsiven Krampftherapie. Ebenfalls deuten erhöhte Neurogeneseraten bei lebenslanger Abwesenheit von Serotonin im ZNS, Therapiemethoden-unabhängig, möglicherweise auf eine modulierte Stressreaktion hin. Untersuchungen der Parameter des HPA-Stressachsensystems, wiesen auf einen grundlegend veränderten Stresshormonspiegel in Tph2-/- Mäusen hin. / Serotonin, the "molecule of happiness" is an important target for antidepressants. The mainly prescribed drugs in major depression are selective serotonin re-uptake inhibitors (SSRI); but recently, SSR-enhancer (SSRE) have also attracted clinical attention. However, only a quarter of patients responds to treatment. It needs to be determined, whether SSRI/E act solely via manipulating serotonin levels or whether other pathways are involved, e.g. neurotrophic signaling (brain-derived neurotrophic factor, BDNF) or the hypothalamus-pituitary-adrenal (HPA)-axis. Furthermore, in major depression, dysregulation of central serotonin signaling is accompanied with a decline in hippocampal neurogenesis, as has been observed in rodent models. At the center of this thesis is a mouse model deficient in the central serotonin-synthesizing enzyme, tryptophan hydroxylase 2 (Tph2-/- mice). I have investigated physiological responses to antidepressant treatment in the absence of brain serotonin, and the possible role of alternative pathways. I observed the typical increase in neurogenesis upon SSRI treatment in WT mice, while it had no effect in Tph2-/- mice. In contrast, BDNF levels were significantly decreased in Tph2-/- mice after treatment with no effect in WT control mice. Furthermore, my results show a critical role of brain serotonin in the neurobiological effects of electroconvulsive seizure. Surprisingly, in animals lacking central serotonin, increased neurogenesis was observed independently of the treatment. The gathered data indicated an altered stress response; therefore, parameters of the HPA-axis have been studied, indicating a downregulated HPA system in Tph2-/-animals in baseline state, but showed no difference in treatment or feedback control. This thesis gives insight into the mechanisms of antidepressant action and reveals ideas for novel pathways involved in the process that could be used as targets in therapeutic approaches and further research in major depression.