Orientador: Cesar Costapinto Santana / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica / Made available in DSpace on 2018-08-04T05:42:04Z (GMT). No. of bitstreams: 1 Goncalves_CarolineVieira_D.pdf: 3183194 bytes, checksum: f2a1cb206fded5b0573c8a68c4578d34 (MD5) Previous issue date: 2005 / Resumo: Fases Estacionárias Quirais (FEQs) têm-se mostrado eficientes na resolução de racematos. O Rolipram, (mais ou menos)-4-(3-(ciclopentiloxi)-4-metoxifenil)-2-pirrolidinona, é um antidepressivo que tem apresentado importantes propriedades farmacológicas. A purificação do Rolipram na FEQ tris(3,5-dimetilfenilcarbamato) de celulose adsorvida em sílica através da cromatografia contínua de Leito Móvel Simulado (LSM) foi o objetivo principal deste trabalho. A FEQ foi sintetizada e suas propriedades foram determinadas por análises físicas e químicas. Através de experimentos de adsorção em coluna forma determinados a influência da temperatura sobre o fator de separação ('alfa¿), as isotermas competitivas da adsorção da mistura racêmica e os parâmetros cinéticos e de equilíbrio da separação do N-Boc-Rolipram na FEQ sintetizada. Os experimentos realizados na unidade LSM foram feitos, sob condições diluídas, á temperatura ambiente. O N-Boc-Rolipram foi separado na FEQ sintetizada através do processo cromatográfico contínuo de LMS. As constantes de adsorção de Henry são discutidas e revelam um fator de separação da ordem de 1,20. AS medidas de pureza e excesso enantiomérico das correntes se extrato e refinado forma determinadas. As analises físicas e químicas da FEQ sintetizada revelam boa concordância com os valores teóricos. Efeitos da temperatura sobre o fator de separação mostram que o processo de adsorção é entalpicamente controlado. Ambos os enantiômeros precisam ser realizados par uma melhor compreensão do processo de adsorção. Os parâmetros de equilíbrio e cinética revelam o bom desempenho da FEQ sintetizada na separação dos enantiômeros principalmente o R-Boc-Rolipram / Abstract: Chiral stationary phases (CSPs) have shown efficiency in racemate purification. Rolipram, (mais ou menos)-4-(3-(cyclopentyloxy)-4-methoxyphenyl)- pyrrolidin-2-one, is an antidepressant with significant pharmacological properties. The main objective of this work was Rolipram purification in the Chiral Stationary Phase tris(3,5-dimethylphenylcarbamoyl) cellulose supported on silica by Simulated Moving Bed continuous chromatography. CSP was synthesized and its properties were determined by physical and chemical analysis. Kinetics and equilibrium parameters of the N-Boc-Rolipram, effect of the temperature on the separation factor (a) and competitive isotherms of the racemic mixture were evaluated by adsorption experiments with columns packed with the synthesized CSP. The experiments in the 5MB unit were carried out under diluted conditions at room temperature. The N-Boc-Rolipram racemate was separated on the synthesized CSP by the 5MB continuous chromatographic processoHenry constants are discussed and reveal Selectivity elose to 1,20. Purity and enantiomeric excess of extract and raffinate streams were determined. Chemicals and physicals analyses of the CSP obtained find good agreement with theoretical results. The effects of the temperature on the separation factor show that adsorption process is controlled by the enthalpy. Both enantiomers adsorb similarly on the synthesized CSP, but detailed studies need to be making for a good understanding of the adsorption processoKinetics and equilibrium parameters show good performance of the synthesized CSP to separate the enantiomers, mainly R-Boc-Rolipram racemate / Doutorado / Desenvolvimento de Processos Biotecnologicos / Doutor em Engenharia Química

Les troubles de l’humeur font partie des problèmes de santé majeurs dans le monde, du fait de leur forte incidence et récurrence dans la population générale, de la nuisance pour la qualité de vie des patients ainsi que la répercussion majeure sur les systèmes de santé. A ce jour, l’étiologie ainsi que les mécanismes biologiques sous-jacents les troubles de l’humeur sous encore très mal connus. Un nombre grandissant de preuves suggère qu’une interaction complexe entre les gènes et l’environnement serait a l’origine de la mise en place et évolution des épisodes dépressifs majeurs – un des troubles de l’humeur les plus répandus. Par conséquent, des régulations épigénétiques complexes, qui consistent en des mécanismes clefs par lesquels l’environnement induit des changements persistant sur l’expression des gènes (sans modifier le code génétique), joueraient un rôle prépondérant dans la pathophysiologie de la dépression. De manière plus spécifique, la répression épigénétique du gène codant pour le brain-derived neurotrophic factor (BDNF) – un facteur de croissance impliqué dans la plasticité neuronale et développement du système nerveux central – serait un mécanisme clef dans la mise en place de la dépression et autres troubles de l’humeur. Dans ce contexte, les travaux de recherche présentés dans cette thèse visent à explorer le rôle des régulations épigénétiques au niveau de la signalisation BDNF/TrkB dans la physiopathologie et traitement des troubles de l’humeur. Les résultats montrent que les régulations épigénétiques au niveau de la signalisation BDNF/TrkB sont fortement impliquées dans la mise en place et maintenance de la plasticité neuronale. De plus, les variations environnementales, particulièrement au cours du développement, sont capables d’induire une reprogrammation épigénétique stable et persistante au niveau du complexe BDNF/TrkB ainsi qu’une altération de la neuroplasticité, conduisant à une augmentation de la vulnérabilité au stress et troubles de l’humeur. De manière intéressante, la signalisation du récepteur TrkB est nécessaire pour les effets neurobiologiques et comportementaux des antidépresseurs. De ce fait, une approche pharmocologique ciblée sur le complexe BDNF/TrkB et ses régulations épigénétiques sous-jacentes apparaît comme stratégie thérapeutique prometteuse pour le traitement des troubles de l’humeur tel que la dépression. / Mood disorders are among the major health problems worldwide due to the high prevalence and recurrence in the general population, and the significant burden for individual life quality and the repercussion on healthcare systems and society. Up to date, the etiology and biological mechanisms underlying mood disorders are still poorly understood. Mounting evidences suggest that a complex interaction between genes and environment might account in the development and course of major depression i.e. one of the most prevalent affective disorders. Accordingly, complex epigenetic regulations - consisting of key mechanisms by which environmental factors induce enduring changes in gene expression without altering the DNA code - have been suspected to plays a pivotal role in the pathophysiology of depression. More specifically, epigenetic repression of the gene encoding for brain-derived neurotrophic factor (BDNF) - a small-secreted growth factor implicated in brain development and neuronal plasticity - may have a preponderant role in the onset of depression and other mood disorders. In this context, the research presented in this thesis aimed at exploring the role of BDNF signaling and its downstream epigenetic regulations in the pathophysiology and treatment of mood disorders. Our findings indicate that epigenetic regulation at BDNF/TrkB signaling is critically important in the establishment and maintenance of neuronal plasticity. Moreover, environmental variations, especially when occurring in development, are able to induce stable and enduring epigenetic reprogramming involving aberrant BDNF/TrkB signaling and impaired neuroplasticity, thereby increasing vulnerability to stress and mood disorders. Interestingly, antidepressants require TrkB to exert some of their neurochemical and behavioral effects. Hence, targeting the BDNF receptor TrkB to restore a normal epigenetic regulation and neuronal functioning appears to be a promising strategy for the treatment of mood disorders.

The term medicalization refers to the process through which a previously nonmedical issue newly becomes conceived of as a medical one. The aim of this thesis is to show how the utilization of this concept can help lead to a better understanding of the contemporary phenomenon of mass antidepressant consumption. I attempt to demonstrate here that the rise in antidepressant use, which has been occurring worldwide in the last few decades, must be understood as the result of a host of factors, among which a key role is played by changes in the conception of certain emotional states, previously understood as normal, as symptoms of mental illness. Aside from a general analysis of the factors that contribute to the consumption of these medications, the thesis also contains my own case study of one of them, namely the ways in which antidepressants are portrayed by the media. I focus on articles, published between the years 1996 and 2016 in Czech national newspapers and attempt to show how discussions about antidepressants, despite their relative neutrality, by accenting a medicalized frame of understanding mental problems help to create an environment, which supports their consumption.

Les douleurs neuropathiques, caractérisées par une prévalence élevée, résultent de la compression ou lésion de nerfs. Les antidépresseurs figurent parmi les traitements de première intention de cette pathologie, toutefois des besoins médicaux restent insatisfaits par ces molécules. Mon travail de thèse s'est intéressé à la connexine 43 (Cx43) astrocytaire impliquée dans le mécanisme d'action des antidépresseurs ainsi que dans les douleurs neuropathiques. La première partie des travaux, réalisée avec des cultures d'astrocytes corticaux de souris, a permis de préciser le lien entre les antidépresseurs et la Cx43 astrocytaire. Alors que son expression s'est avérée inchangée dans notre modèle, un effet hétérogène des antidépresseurs a été observé sur le couplage intercellulaire des astrocytes. L'ensemble des molécules testées a conduit à l'inhibition de l'ouverture des hémicanaux de Cx43 étudiée dans un contexte inflammatoire, notre étude est la première à rapporter cet effet. De plus, les antidépresseurs prescrits dans les douleurs neuropathiques ont induit l'inhibition du couplage et/ou des hémicanaux. La seconde partie de mes travaux a porté sur la combinaison entre l'amitriptyline et la méfloquine. Ceci repose sur les approches combinatoires proposées par Theranexus, start-up avec qui la thèse a été réalisée. Les deux molécules ont présenté une synergie d'effet sur la réduction du couplage astrocytaire in vitro corrélée a une potentialisation de l'action anti-hyperalgésique de l'amitriptyline in vivo, chez le rat lésé au niveau du nerf sciatique. Ces résultats valident l'implication de la Cx43 astrocytaire dans la réponse antinociceptive des antidépresseurs. / Neuropathic pain, characterised by a marked prevalence, is the consequence of nerve compression or lesion. Antidepressants represent the main treatments of this disease, however, medical needs remain mostly unsatisfied by these molecules. In order to improve this therapeutical approach, my thesis work has focussed on astroglial connexin 43 (Cx43) that has recently been involved in the mechanism of action of antidepressant as well as in neuropathic pain. The first part of my work, performed in primary cultures of mouse cortical astrocytes, has allowed to reinforce the link between antidepressants and Cx43 in astrocytes. Whereas its expression was unchanged in our model, an heterogeneous effect of antidepressants was observed on the intercellular communication of astrocytes. Furthermore, all tested molecules led to the inhibition of Cx43 hemichannel activity in an inflammatory context, our study is the first to report such effect. Interestingly, antidepressants prescribed in neuropathic pain induced inhibition of coupling and/or hemichannels. The second part of my work concerned the combination between amitriptyline and mefloquine. This is based on combinatorial approaches proposed by Theranexus, a start-up partner in this project. The association of the two molecules presented a synergy on astroglial coupling reduction in vitro correlated to a potentiation of the anti-hyperalgesic effect of amitriptyline in vivo, in rats with injured sciatic nerve. These results confirm the implication of the astroglial Cx43 in the antinociceptive response to antidepressants.

Certain electrophysiological markers hold promise in distinguishing individuals with major depressive disorder (MDD) and in predicting antidepressant response, thereby assisting with assessment and optimizing treatment, respectively. This thesis examined resting brain activity via electroencephalographic (EEG) recordings, as well as EEG-derived event-related potentials (ERPs) to auditory stimuli and facial expression presentations in individuals with MDD and controls. Additionally, the utility of resting EEG as well as auditory ERPs (AEPs), and the associated loudness-dependence of AEPs (LDAEP) slope, were assessed in predicating outcome to chronic treatment with one of three antidepressant regimens [escitalopram (ESC); bupropion (BUP); ESC+BUP]. Relative to controls, depressed adults had lower pretreatment cortical activity in regions implicated in approach motives/positive processing. Increased anterior cingulate cortex (ACC)-localized theta was observed, possibly reflecting emotion/cognitive regulation disturbances in the disorder. AEPs and LDAEPs, putative indices of serotonin activity (implicated in MDD etiology), were largely unaltered in MDD. Assessment of ERPs to facial expression processing indicated slightly blunted late preconscious perceptual processing of expressions, and prolonged processing of intensely sad faces in MDD. Faces were rated as sadder overall in MDD, indicating a negative processing bias. Treatment responders (vs. non-responders) exhibited baseline cortical hypoactivity; after a week of treatment, cortical arousal emerged in responders. Increased baseline left fronto-cortical activity and early shifts towards this profile were noted in responders (vs. non-responders). Responders exhibited a steep, and non-responders shallow, baseline N1 LDAEP derived from primary auditory cortex activity. P2 LDAEP slopes (primary auditory cortex-derived) increased after a week of treatment in responders and decreased in non-responders. Consistent with overall findings, ESC responders displayed baseline cortical hypoactivity and steep LDAEP-sLORETA slopes (vs. non-responders). BUP responders also exhibited steep baseline slopes and high ACC theta. These results indicate that specific resting brain activity profiles appear to distinguish depressed from non-depressed individuals. Subtle ERP modulations to simple auditory and emotive processing also existed in MDD. Resting alpha power, ACC theta activity and LDAEP slopes predicted antidepressant response in general, but were limited in predicting outcome to a particular treatment, which may be associated with limited sample sizes.

Bakgrund: Medicinering med antidepressiva läkemedel ökar i samhället. Statistikur Socialstyrelsens databas för läkemedel från 2017, visar att 632 000 personer iSverige medicineras med antidepressiva. Studier visar att även om patientenförväntar sig att vårdpersonal informerar om läkemedelsbiverkningar såsomsexuella biverkningar görs det inte. Genom att tidigare forskning visade attsjuksköterskor känner sig obekväma trots att biverkningsprofilen är känd, väcktesett intresse att undersöka vidare hur och varför samtal om sexuella biverkningar iomvårdnaden verkar hamna längre ner i prioriteringen.Syfte: Syftet var att genom intervjuer undersöka sjuksköterskors erfarenheter avatt samtala med psykiatriska patienter om sexuella biverkningar vid behandlingmed antidepressiva läkemedel.Metod: Efter godkänd etikansökan från Malmö Universitet utformandes ensemistrukturerad intervjuguide, både allmänsjuksköterskor samt psykiatrisjuksköterskordeltog. Tio intervjuer utfördes på informanternas arbetsplats.Intervjuerna spelades in digitalt och varade mellan 15 och 30 minuter.Transkribering gjordes efter varje intervju. Texten analyserades enligt enmodifierad version av Burnard (1991).Resultat: Följande kategorier identifierades i resultatet: Att samtala om sexuellabiverkningar, att möta patienten och att undvika frågan. Resultatet påvisade att deflesta sjuksköterskor inte samtalar om sexuella biverkningar. Delvis på grund avde anser det vara pinsamt, men även på grund av de anser sig besitta begränsadkunskap inom området.Diskussion: Sjuksköterskorna var i behov av ökad kunskap och utbildning för attde skulle känna sig trygga att samtala om sexuella biverkningar med patienterna.En etablerad relation visade sig göra ämnet enklare att samtala om, dock fanns detofta ett hinder för detta, vilket var tidsbrist. Något som även visade sig göra ämnetproblematiskt var att sju / Background: Medication with antidepressant drugs increases in society. Statisticsfrom the National Board of Health's Drugs database from 2017 show that 632,000people in Sweden are being treated with antidepressants. Studies show thatalthough the patient expects healthcare professionals to inform about drug sideeffects such as sexual side effects, it is not done. Because previous researchshowed that nurses feel uncomfortable even though the side effects profile isknown, an interest was raised to further investigate how and why discussingsexual side effects seems to be less prioritized in nursing.Aim: The aim was to investigate, through interviews, the nurse's experience oftalking with psychiatric patients about sexual side effects in treatment withantidepressant drugs.Method: After an approved ethics application from Malmö University, a semistructuredinterview guide was drafted involving both general nurses andpsychiatric nurses. Ten interviews were conducted and lasted between 15-30minutes and were recorded with mobile phones. The interviews were conducted atthe informants' workplace at a time chosen by the informant. Each interview wastranscribed, and the analysis was made according to a modified version ofBurnard’s method (1991).Result: The following categories were identified in the result: To talk about sexualside effects, to meet the patient and to avoid the question. The result showed thatmost nurses do not talk about sexual side effects. Partly because they consider itembarrassing, but also because they consider themselves possessing limitedknowledge in the area.Discussion: Nurses needed to increase their knowledge and education to makethem feel assured when talking about sexual side effects with patients. Anestablished relationship made the topic easier to talk about, but time shortage wasan obstacle to this. Something that also proved to be problematic was the nurseslack of routines for conversations about sexual side effects.

Dans cette thèse, nous avons étudié la relation entre le traitement par antidépresseurs, la prise du poids et le syndrome métabolique sur un échantillon de patients atteints de TDM. Les résultats cliniques ont suggéré que la prise du poids précoce due au traitement par antidépresseurs augmenterait le risque de prise du poids ultérieure et d’incidence ultérieure du syndrome métabolique. Ainsi que la relation entre l'utilisation des antidépresseurs, la réponse au traitement et la prise du poids reste complexe. Malgré l'augmentation simultanée de la consommation d'antidépresseurs et la tendance à l'obésité dans les sociétés occidentales, des cohortes prospectives supplémentaires sont nécessaires pour tester pleinement l'hypothèse traitant que la prise du poids chez les utilisateurs des antidépresseurs est un effet iatrogène. Bien que l'impact des antidépresseurs sur la morbidité cardiovasculaire ne puisse toujours pas être déterminé, les résultats du premier chapitre ont montré que l'utilisation des antidépresseurs, indépendamment de leurs classes, avait un impact sur les dérèglements métaboliques, nécessitant une attention clinique spécifique. Une étude de cohorte à long terme est nécessaire pour confirmer si l'interruption et la réinstauration du traitement par des antidépresseurs seraient liées à la fluctuation des dysrégulations du syndrome métabolique. / In this dissertation we have studied the relationship between AD treatment, weight gain and MetS on a sample of MDD patients. Clinical findings have suggested that early weight gain due to AD treatment would increase the risk of both later weight gain and later MetS incidence. The relationship between AD use, response to treatment and weight gain remain complex. Despite the simultaneous increase in AD use and obesity trends in Western societies, additional prospective cohorts are needed to fully test the hypothesis that weight gain among AD users is indeed an iatrogenic effect. Although impact of AD on cardiovascular morbidity still cannot be ascertained, the results from the first chapter showed that AD use – irrespective of the class - does impact and worsen metabolic dysregulations, which would require specific clinical attention. A long term cohort study is required to confirm whether discontinuation and re-initiation of AD treatment would be linked to fluctuation in MetS dysregulations.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23408号 / 医博第4753号 / 新制||医||1052(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中山 健夫, 教授 古川 壽亮, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

La dépression majeure représente l’une des affections les plus lourdes dans le monde, touchant plus de 350 millions depersonnes. La 5e édition du Diagnostic and Statistical Manual of Mental Disorders (DSM-V) est la référence mondiale utiliséepour poser le diagnostic de la pathologie chez l’humain. Bien que très nombreux, les antidépresseurs prescrits à ce jour restentencore malheureusement inefficaces pour 30% des patients. Dans ce contexte, il est fondamental de développer de nouvellesstratégies thérapeutiques pour soigner les patients. Des études récentes suggèrent, sans toutefois le démontrer véritablement,l’implication de l’axe « activateur tissulaire du plasminogène / inhibiteur de l’activateur tissulaire du plasminogène de type 1 »(axe tPA/PAI-1) dans la pathogenèse de la dépression majeure.La première partie de mes travaux a été consacrée à la mise au point d’un nouveau système d’évaluation comportementalede la dépression majeure chez la souris en modélisant de manière exhaustive et standardisée les symptômes cliniques du DSMV.La seconde partie de mes travaux a consisté à étudier les mécanismes d’action potentiels de l’axe tPA/PAI-1 dans ladépression majeure. Pour ce faire, j’ai tout d’abord caractérisé le phénotype comportemental de souris déficientes en tPA (souristPA-/-) et en PAI-1 (souris PAI-1-/-), ainsi que de leurs homologues de type sauvage, grâce au système fonctionnel d’évaluationinitialement mis en place. Par ailleurs, du fait de la forte comorbidité entre anxiété et dépression, les comportements de typeanxieux ont également été analysés chez ces animaux. Mes expériences ont révélé un phénotype de type dépressif, indépendantdu tPA, chez les souris déficientes en PAI-1, associé à des diminutions des concentrations de deux monoamines (sérotonine etdopamine) dans des structures cérébrales connues pour être impliquées dans la dépression majeure (hippocampe et noyau du litde la strie terminale). De surcroît, l’enrichissement modéré de l’environnement n’amenuise pas les symptômes de type dépressifdes souris PAI-1-/- mais conduit cependant à la disparition des troubles anxieux dépendants, quant à eux, de l’axe tPA/PAI-1.La troisième partie de ma thèse a été dédiée à des manipulations pharmacologiques visant à tester l’efficacitéd’antidépresseurs de type inhibiteurs de la recapture de la sérotonine. L’escitalopram produit un effet anxiolytique chez les sourisdéficientes en PAI-1, sans toutefois contrebalancer le phénotype dépressif chez ces mêmes sujets. Qui plus est, la fluoxétine, àla même dose que l’escitalopram, est toxique pour ces souris.Les résultats de ma thèse apportent ainsi la première démonstration de l’implication de PAI-1 dans la dépression majeurepar un mécanisme indépendant de son interaction avec le tPA. Ces travaux démontrent également que la souris PAI-1-/- constitueun outil essentiel et innovant pour étudier les mécanismes cellulaires et moléculaires sous-jacents à la dépression majeure, ainsique pour la recherche de cibles thérapeutiques visant à améliorer l’efficacité des traitements. / Major depressive disorder is one of the heaviest mental disorders in the world, affecting more than 350 people worldwide.It is in the fifth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) that the basis for an internationallyadmitted diagnosis was laid. Albeit diverse, existing antidepressants still remain ineffective for 30% of the patients. Under suchcircumstances, the necessity of developing new therapeutical strategies has arisen. Recent studies tend to suggest, withoutabsolute demonstration, the implication of the axis "Tissue Plasminogen Activator / Plasminogen Activator Inhibitor type-1"(tPA/PAI-1 axis) in the pathogenesis of major depressive disorders.The first section of my works has been devoted to the development of a new system of behavioural assessment in micefor depressive-like disorders, through a comprehensive and standardised modelling of clinical symptoms of DSM-V.The second section of my works has consisted in studying the potential action mechanisms of the tPA/PAI-1 axis in theemergence of depressive-like disorders. To do so, I first had to identify the behavioural phenotype of mice having from a tPA(tPA-/- mice) and PAI-1 (PAI-1-/-mice) deficiency as well as their wild-type counterparts through the system of assessment setup in the beginning of my research. In addition, due to the significant comorbidity between anxiety and depression, anxious-likebehaviours have been analysed as well. Among PAI-1-deficient mice, my experiments have disclosed a depressive-likephenotype, independent of tPA, and correlated with a decrease in the concentration of two monoamines (serotonin and dopamine)in brain structures known to be involved in major depressive disorder (hippocampus and bed nucleus of the stria terminalis).Besides, the moderate enrichment of the environment does not reduce the depressive-like symptoms of PAI-1-/- mice, yet inducesthe dissipation of dependent-tPA/PAI-1 axis anxious disorders.The third section of my PhD has been devoted to pharmacological experiments meant to assess the effectiveness ofantidepressants classified among selective serotonin reuptake inhibitors (SSRIs). Escitalopram produces anxiolytic falloutsamong PAI-1-deficient mice without for all that offsetting the depressive phenotype among these same mice. Moreover,fluoxetine administered in the same concentration as escitalopram has proven to be toxic for these mice.The results of these doctoral experiments have therefore demonstrated for the first time the implication of PAI-1 in theprocess of major depressive disorder through a mechanism independent from its interaction with tPA. These works have alsodemonstrated that PAI-1-/- mice make up a fundamental and cutting edge tool to study the cellular and molecular mechanismsunderlying major depressive disorder as well as to develop competent therapeutical targets intended to improve the efficiency oftreatments.

L’analyse de donnée textuelle est facilitée par l’utilisation du text mining (TM) permettant l’automatisation de l’analyse de contenu et possède de nombreuses applications en santé. L’une d’entre elles est l’utilisation du TM pour explorer le contenu des messages échangés sur Internet.Nous avons effectué une revue de la littérature systématique afin d’identifier les applications du TM en santé mentale. De plus, le TM a permis d’explorer les préoccupations des utilisateurs du forum Doctissimo.com au sujet des antidépresseurs et anxiolytiques entre 2013 et 2015 via l’analyse des fréquences des mots, des cooccurrences, de la modélisation thématique (LDA) et de la popularité des thèmes.Les quatre applications du TM en santé mentale sont l’analyse des récits des patients (psychopathologie), le ressenti exprimé sur Internet, le contenu des dossiers médicaux, et les thèmes de la littérature médicale. Quatre grands thèmes ont été identifiés sur le forum: le sevrage (le plus fréquent), l’escitalopram, l’anxiété de l’effet du traitement et les effets secondaires. Alors que les effets indésirables des traitements est un sujet qui a tendance à décroitre, les interrogations sur les effets du sevrage et le changement de traitement sont grandissantes et associées aux antidépresseurs.L’analyse du contenu d’Internet permet de comprendre les préoccupations des patients et le soutien, et améliorer l’adhérence au traitement. / Analysis of textual data is facilitated by the use of text mining (TM) allowing to automate content analysis, and is implemented in several application in healthcare. These include the use of TM to explore the content of posts shared online.We performed a systematique literature review to identify the application of TM in psychiatry. In addition, we used TM to explore users’ concerns of an online forum dedicated to antidepressants and anxiolytics between 2013 and 2015 analysing words frequency, cooccurences, topic models (LDA) and popularity of topics.The four TM applications in psychiatry retrieved are the analysis of patients' narratives (psychopathology), feelings expressed online, content of medical records, and biomedical literature screening. Four topics are identified on the forum: withdrawals (most frequent), escitalopram, anxiety related to treatment effect and secondary effects. While concerns around secondary effects of treatment declined, questions about withdrawals effects and changing medication increased related to several antidepressants.Content analysis of online textual data allow us to better understand major concerns of patients, support provided, and to improve the adherence of treatment.