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Posttraumatic stress disorder (PTSD) is classified as an anxiety disorder and the characteristic symptoms (re-experiencing, avoidance as well as numbing of general responsiveness and hyperarousal) of this disorder develop in response to a traumatic event. The disorder is characterised by hypothalamic-pituitary-adrenal (HPA) axis abnormalities linked with changes in cortisol moreover, the hippocampus and cortex also play a role in the neurobiology. With regard to the neurochemistry of this disorder it is known that gamma amino butyric acid (GABA) is involved however, the precise role of GABA in PTSD and how stress changes GABA concentrations in the brain are still not fully understood. Another aspect regarding PTSD that has not been clearly defined is the treatment of PTSD. Classic anxiolytics such as diazepam is expected to relieve the anxiety linked with PTSD. Studies with this group of drugs have however not produced the concrete evidence needed to establish it as a treatment of choice for PTSD and subsequently other classes of drugs have been investigated as possible treatment options for PTSD. Among these is lamotrigine, which in a clinical study was found to be effective in alleviating symptoms of PTSD. Moreover, a possible pharmacokinetic-pharmacodynamic relationship for each of these drugs has also not been elucidated. In order to elude on some of these uncertainties, an animal model of PTSD, time dependent sensitisation (TDS), was used. GABA levels in the rat hippocampus and frontal cortex were determined at two different time intervals following the TDS procedure (1 day and 7 days post re-stress). High performance liquid chromatography (HPLC) with electrochemical (EC) detection was used to determine gamma amino butyric acid (GABA) concentrations. To investigate the possible anxiolytic effects of diazepam and lamotrigine in this model, as well as a possible pharmacokinetic-pharmacodynamic relationship for each drug, pharmacokinetic profiles for both drugs were established in order to find the times of peak and trough levels of each drug. Blood samples were collected at different time intervals after drug administration either from the tail vein of rats (lamotrigine) or directly from the heart (diazepam). Subsequently, drug concentrations at each time interval were determined by means of HPLC with ultraviolet (UV) detection. The behaviour of rats was analysed using the elevated plus-maze (EPM) at peak or trough concentrations of the drugs and this was performed after either acute administration of the drug, or after a 14 day chronic treatment regime. GABA levels in the hippocampus were not found to change statistically significantly in response to stress at either 1 day or 7 days post re-stress. In the frontal cortex, however, GABA levels increased in response to stress at 1 day post re-stress, with a statistically insignificant, but strong trend towards an increase, at 7 days post re-stress. With regard to the pharmacokinetic profiles, the peak concentration of diazepam was found to occur at 60 minutes, with lamotrigine's peak at 120 minutes. The behavioural studies indicated that acute treatment with diazepam 3 mg/kg resulted in a statistically significant increase in both ratio open arm entries and ratio time spent in the open arms at peak level of the drug. After acute treatment with diazepam 3 mg/kg a statistically significant decrease in ratio time spent in open arms was also found when the ratio time spent in open arms at peak level of the drug and the ratio time spent in open arms at trough level of the drug was compared. In response to chronic treatment with diazepam 3 mg/kg for 14 days, test animals exhibited an increase in the ratio open arm entries at trough level of the drug, with a statistically insignificant yet definite trend towards an increase at peak level. Acute treatment with lamotrigine 10 mg/kg resulted in no statistically significant change in EPM parameters. In response to chronic treatment, however, a statistically significant increase was found in ratio time spent in open arms at peak level of the drug, with a statistically insignificant trend towards an increase at trough level. From the results of this study, we may therefore conclude that GABA-levels in the brain are definitely affected, but in different ways, following TDS-stress. A pharmacokinetic-pharmacodynamic relationship between the drugs' levels and aversive behaviour could also be established. Furthermore it appears that more sustained anxiolytic effects are evident following chronic treatment with both drugs than with acute administration of these drugs. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2006

Posttraumatic stress disorder (PTSD) is an anxiety disorder that may follow exposure to severe emotional trauma and presents with various symptoms of anxiety, hyperarousal and cognitive anomalies. Interestingly, only 10-30% of an exposed population will go on to develop full-blown PTSD. Cholinergic neurotransmission is implicated in anxiety as well as other typical manifestations of PTSD, particularly cognitive changes. The frontal cortex and hippocampus regulate and in turn are affected by stress, and have also been implicated in the underlying neuropathology of PTSD. These areas are densely innervated by cholinergic neurons originating from the basal forebrain. In this study, the time dependent sensitization (TDS) model was used to induce symptoms of PTSD in animals. The study was designed to determine the long-term effects of an intense, prolonged aversive procedure on central muscarinic acetylcholine receptor (mAChR) characteristics and the correlation if any of those findings to cognitive aspects and general arousal as characteristics associated with PTSD. In order to achieve this goal, male Sprague-Dawley rats were exposed to the TDS stress paradigm with behavioral/neuro-receptor assessments performed on day 7 post re-stress (duration of each experiment in whole is 14 days). Acoustic startle reflex (ASR) was used to determine emotional state (hyperarousal), while the conditioned taste aversion (CTA) paradigm was implemented in order to assess aversive memory. Muscarinic receptor binding studies were performed in the frontal cortex and hippocampus. Moreover, both the stress-exposed and control animals were pre-tested in the acoustic startle chamber in order to attempt to separate stress sensitive from stress-resilient animals based on predetermined ASR criteria. The ASR niodel was previously validated in our laboratory, while the CTA model was validated in this project before application. In the CTA model, an i.p. injection with lithium chloride (LiCl) (associated with digestive malaise), was used as unconditioned stimulus (US) and was paired with a saccharinlcyclamate drinking solution as conditioned stimulus (CS) to induce aversion to the novel taste (CS) when presented in the absence of the US. Population data of animals tested in the ASR experiment indicated no statistical significant difference between stressed and control animals. However, when each animal was assessed individually, 22.5 % of the exposed population displayed all increase above the predetermined criteria of 35 % in startle response, indicating a state of heightened arousal. In contrast, only 4.2 O h of control animals (no stress) displayed an increase in arousal based on the above mentioned criteria. Muscarinic receptor densities (Bm,) in the total population of animals exposed to stress showed a statistical significant increase in both the hippocampus and frontal cortex when compared to controls, with no changes in & values observed in either one of the areas. In the CTA experiment, TDS stress was implemented as US paired with a saccharinlcyclamate drinking solution as CS. An acute session of prolonged stress (as used in the TDS model) effectively induced aversion to a novel taste and a subsequent reminder of the stress (restress) paired with the CS sustained the acquire adversive memory. Furthermore, LiCl was reintroduced as US in order to assess the effect of prior exposure to two types of stress (acute and TDS) on subsequently acquired CTA memory. Prior exposure to acute stress had no significant effect on subsequently acquired aversive memory when measured either 3- or 7 days post-conditioning (CS-US). Stress-restress (TDS) exposure, however, indicated a significant decrease in aversive memory from 3- to 7 days post-conditioning (CS-US) as well as a significant decrease in aversive memory between the control- and the TDS group 7 days post-conditioning. The mAChR density (B,,) in the frontal cortex; but not in the hippocampus, was elevated at the same point in time (7 days post CS-US pairing) that CTA memory was impaired following TDS stress (stress-restress). Ultimately, these data support an association between altered cholinergic receptors and hyperarousallanxiety in an animal model of PTSD. The data also support the phenomenon of individual susceptibility to stress in animals that parallels that observed in humans exposed to severe trauma. Impaired aversive memory (CTA) is a consequence of prior exposure to TDS stress, but not acute stress, and is likewise mediated by an altered central cholinergic transmission displayed as an increase in mAChRs in the frontal cortex. The lack of studies regarding the influence of the cholinergic system in PTSD related behavior earns ,this project value as inimitable PTSD research. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2007.

La présente thèse porte sur l’évaluation de l’efficacité d’un nouveau traitement pour le trouble de stress post-traumatique (TSPT). Le traitement a été développé selon les prémisses de la théorie de la reconsolidation des souvenirs. Il consiste en six courtes séances de remémoration de l’événement traumatique réalisées sous l’effet du propranolol, un bêtabloquant. La population de l’étude est constituée de patients souffrant d’un TSPT chronique. La thèse comporte cinq chapitres. Le premier chapitre est l’introduction, on y retrouve une description du TSPT, des traitements validés empiriquement, de diverses théories de la mémoire, d’un modèle étiologique du TSPT, d’études sur la consolidation et la reconsolidation, de la pharmacocinétique et du mécanisme d’action du propranolol,ainsi que des objectifs de la thèse. Le second chapitre est une revue critique de littérature sur la théorie de la reconsolidation. Comme l’étude du phénomène de la reconsolidation est récente, nous tentons de faire le point sur l’état des connaissances dans le domaine, dans un effort de réflexion sur la validité de la théorie. Nous proposons une série de critères permettant de différencier la reconsolidation d’autres processus connexes. Nous concluons que la théorie paraît valide, bien que d’autres études soient nécessaires afin de rendre compte de résultats négatifs publiés par le passé. Le troisième chapitre est un essai ouvert, et vise à évaluer l’efficacité d’un traitement basé sur la reconsolidation à diminuer la sévérité et l’incidence du TSPT, auprès de 42 patients souffrant d’un TSPT chronique. Le traitement consiste en six séances de remémoration de l’événement traumatique sous propranolol. Lors d’un suivi à trois mois, nous rapportons une diminution des symptômes de TSPT de 41%-56%, ainsi qu’une diminution de l’incidence du TSPT de 74%. En comparaison, seulement 2/25 patients du groupe contrôle (ayant participé uniquement aux évaluations) ne souffrent plus d’un TSPT. Dans le groupe traitement, les tailles d’effet (d de Cohen)varient entre 1.32-2.19. Le quatrième chapitre a comme objectif d’identifier des caractéristiques des patients prédisant l’efficacité du traitement, et d’explorer s’ils s’améliorent dans des domaines de santé autres que le TSPT. Nous rapportons que les femmes s’améliorent davantage que les hommes, mais que d’autres facteurs, tels que la sévérité des traits de personnalité borderline ou le type de trauma (enfance versus adulte), n’influent pas sur l’efficacité. Également, les patients s’améliorent dans les domaines de santé suivants : la qualité de vie, la symptomatologie dépressive, l’intensité des émotions négatives au rappel de l’événement traumatique et dans la vie courante. Le cinquième chapitre contient la discussion générale de la thèse. Nous effectuons une synthèse et interprétation des résultats, nous examinons les hypothèses alternatives à l’amélioration clinique et abordons des pistes de recherches futures. Nous concluons que le traitement à l’étude a été efficace dans notre échantillon de patients souffrant d’un TSPT chronique. Étant donné la méthodologie employée (essai ouvert), nous ne pouvons statuer sur le mécanisme d’action du traitement, à savoir si l’amélioration clinique a été réellement causée par un blocage de la reconsolidation des souvenirs. / This dissertation aims at exploring the efficacy of a new treatment for posttraumatic stress disorder (PTSD). The treatment was developed in accordance with an emerging theory in neuroscience, the reconsolidation theory, and it consists in six short reactivation sessions of a traumatic memory under the influence of propranolol (a ß-blocker), with patients suffering from longstanding PTSD. This dissertation includes five chapters. Chapter I is the introduction, it includes a discussion on the following topics : definition and prevalence of PTSD,empirically validated treatments in the field, memory theories, etiology of PTSD, studies on consolidation and reconsolidation, pharmacokinetics of propranolol and its mechanism of action in reconsolidation, and the objectives of the dissertation. Chapter II is a critical literature review on reconsolidation theory. We discuss some of the contradicting findings in reconsolidation, as some researchers have reported negative results in the field. We address the possibility to reconcile these discrepancies,within the scope of evaluating the validity of the theory. We also discuss a series of criterion which could provide guidance in differentiating reconsolidation from other processes. We conclude that reconsolidation theory seems valid, although more research is needed in order to shed light on some negative results that were published in the past. Chapter III is an open label trial comprising six sessions of treatment (trauma reactivation under propranolol) with 42 patients suffering from chronic PTSD. At a three-month follow-up, we report that patients have a 41% - 56% reduction in PTSD symptoms, and that 31 / 42 patients no longer meet the diagnostic threshold for PTSD. In comparison, only 2 / 25 patients from the control group (assessments only) don’t meet the diagnostic threshold for PTSD. In the treatment group, effect sizes (Cohen’s d) range between 1.32 -2.19. Chapter IV follows on the previous chapter’s study, and aims at identifying predictors of treatment outcome (i.e., predictors of the improvement in PTSD symptoms), and whether patients also improve in health domains other than PTSD. We report that women improve more than men during the treatment, but that other factors such as borderline personality severity traits or type of trauma (childhood versus adulthood) do not influence treatment outcome. Patients also improve in diverse health domains during the treatment; they have a better quality of life, less depressive symptoms, less intense negative emotions in daily life and during trauma recollection. Chapter V contains a general discussion and a conclusion. We summarize and interpret the results, we explore alternative hypotheses to the clinical improvement as well as future research directions. We conclude that this treatment yielded interesting results in our sample of patients suffering from chronic PTSD. However, our methodology (open label study) doesn’t provide any information on the mechanism of action of the treatment used in this dissertation, i.e. whether the clinical improvement was caused or not by reconsolidation blockade.

Une récente théorie de la mémoire a proposé que lorsqu'un souvenir déjà bien consolidé est réactivé, il redevient labile et susceptible aux modifications avant d'être restabilisé (reconsolidé) en mémoire à long terme. Ce nouveau modèle réfute le modèle classique de la consolidation qui propose qu'une fois consolidés, les souvenirs soient permanents et donc résistants aux effets des agents amnésiques. Les études validant la théorie de la reconsolidation abondent chez les animaux, mais encore peu d'études ont été réalisées chez les humains. L'objectif de cette thèse est de vérifier, dans une population de sujets sains et de sujets souffrant de trouble de stress post-traumatique (TSPT), l'efficacité d'un agent pharmacologique, le propranolol (un β-bloquant noradrénergique) à atténuer des souvenirs émotionnels nouvellement acquis ou déjà bien consolidés. Plus spécifiquement, nous avons mené un essai clinique contrôlé à double insu chez des sujets sains en leur administrant du propranolol (vs du placebo) lors de l'acquisition d'un nouveau souvenir et une semaine plus tard, lors de sa réactivation. L'objectif du premier article était d'évaluer l'efficacité du propranolol à diminuer la consolidation et la reconsolidation d'un souvenir émotionnel. Par ailleurs, puisque les études chez les animaux ont démontré que ces deux processus mnésiques s'effectuent à l'intérieur d'une fenêtre temporelle précise, le moment de l'administration du propranolol fut pris en considération. Les résultats ont démontré que le propranolol est en mesure de diminuer la consolidation et la reconsolidation d'une histoire émotionnelle tel que démontré par un pourcentage de bonnes réponses plus faible que le groupe contrôle lors des rappels. Toutefois, pour que cet effet soit observé, le propranolol doit être administré une heure avant la présentation des stimuli, pour la consolidation et une heure avant leur réactivation, pour la reconsolidation. En outre, les études portant sur la consolidation et la reconsolidation chez les animaux et chez les humains obtiennent parfois des résultats contradictoires. Ceci pourrait s'expliquer par le type de stimuli utilisé. Ainsi, l'objectif du second article était de préciser quel type d'information est le plus susceptible d'être affecté par le propranolol lors de son acquisition (consolidation) et lors de sa réactivation (reconsolidation). Pour ce faire, les éléments de l'histoire émotionnelle ont été divisés en fonction de leur valence (émotionnel ou neutre) et de leur centralité (central ou périphérique). Les résultats ont démontré le propranolol affecte l'ensemble des informations centrales lors du blocage de la consolidation, mais qu'il affecte plus spécifiquement les éléments émotionnels centraux lors de la reconsolidation. Notre groupe ayant précédemment démontré que le traitement avec le propranolol est en mesure de réduire les symptômes de TSPT chez une population clinique, nous nous sommes interrogés sur son efficacité à diminuer la mémoire implicite d'un événement traumatique. Le propranolol a été administré aux participants à 6 reprises (une fois par semaine sur une période de 6 semaines) lors de la réactivation de leur trauma. Les résultats ont révélé que le traitement avec le propranolol est en mesure de diminuer la réponse psychophysiologique des participants à l'écoute du compte rendu de leur trauma une semaine et 4 mois suivant la fin du traitement. En somme, cette thèse démontre que le propranolol est en mesure de bloquer la consolidation et la reconsolidation de souvenirs émotionnels chez l'humain lorsqu'il est administré une heure avant l'acquisition ou la réactivation des souvenirs. Il arrive en outre à atténuer un souvenir déclaratif émotionnel chez des sujets sains, mais également un souvenir implicite chez des sujets souffrant de TSPT. Ainsi, ces résultats ouvrent la voie à la création de nouveaux traitements pour les psychopathologies ayant comme étiologie un souvenir émotionnel intense. / A recent theory of memory proposes that when a well-consolidated memory is reactivated, it becomes labile again and susceptible to change before being restabilized (reconsolidated) in long-term memory. This new memory theory refutes the classical model of consolidation, which suggests that once consolidated, memories are permanent and hence resistant to the effects of amnestic agents. Studies validating reconsolidation theory in animals abound, but fewer studies have been conducted in humans. The objective of the current thesis is to verify the potential of the pharmacological agent propranolol (a β-blocker) to impair newly acquired or already consolidated emotional memories in healthy subjects and subjects suffering from posttraumatic stress disorder (PTSD). We conducted a double blind controlled trial where propranolol (vs. placebo) was administered to healthy subjects during the acquisition of a new memory (an emotionally valenced story) and one week later, during its reactivation. The aim of the first paper was to evaluate the efficacy of propranolol to reduce the consolidation and reconsolidation of emotional memories. Furthermore, since animal studies have shown that these two memory processes occur within a given time window, the timing of the propranolol administration was taken into consideration. The results showed that propranolol was able to dampen the consolidation and reconsolidation of an emotional story as evidenced by a lower percentage of correct answers at recall compared to the control group. However, to observe this effect, the propranolol needed to be administered one hour before the presentation of the story at consolidation and one hour before it’s reactivation at reconsolidation. While consolidation and reconsolidation studies in animals and humans have yielded conflicting results, this may depend on the type of stimuli used. The objective of the second paper of this thesis was to determine what type of information is most likely to be affected by propranolol during acquisition (consolidation) and reactivation (reconsolidation). To do this, the elements of the emotional story were divided according their emotionality (emotional vs. neutral) and centrality (central vs. peripheral). The results demonstrated that propranolol blocks the consolidation of all central information, but it affects selectively the central-emotional story elements at reconsolidation. Our group previously demonstrated that treatment with propranolol is able to reduce the symptoms of PTSD in a clinical population. In this thesis, we investigated whether it could also reduce the implicit memory of a traumatic event. Propranolol was administered on 6 different occasions (once a week over a period of 6 weeks) to participants upon reactivation of their traumatic event. The results unveiled that treatment with propranolol was able to decrease the participants’ psychophysiological responses to their traumatic script at one week post-treatment and at the 4 months follow-up. In sum, this thesis reports results suggesting that propranolol is able to block the consolidation and reconsolidation of emotional memories in humans when it is administered one hour before acquisition or before reactivation. Furthermore, this thesis suggests that propranolol impairs selectively central-emotional type of information and that it has the ability to dampen declarative emotional memory in healthy subjects, but also implicit memory in subjects suffering from PTSD. Hence, these results open the way to create new treatments for psychopathologies having at their core an intense emotional memory

Borderline-Persönlichkeitsstörung (BPS) ist eine schwere psychiatrische Störung, die durch tiefgreifende Probleme in Emotionsregulation und zwischenmenschlichen Beziehungen gekennzeichnet ist. Die gestörten Beziehungsmuster werden als ein Kernmerkmal von BPS betrachtet, obwohl die empirische Evidenz dafür weitestgehend fehlt. Bisherige Ergebnisse sind auf behavioraler und neuronaler Ebene bei BPS durch das häufig komorbide Auftreten einer posttraumatischen Belastungsstörung (PTBS) verzerrt. Eine vielversprechende Möglichkeit, die Beziehungsstörung von Patienten mit BPS näher zu untersuchen, bietet das multidimensionale Konzept der Empathie. Daher konzentriert sich die vorliegende Arbeit auf die Identifizierung behavioraler und neuronaler Korrelate kognitiver und emotionaler Empathie bei BPS Patienten und den Einfluss einer komorbiden PTBS auf diese. Die Ergebnisse zeigen, dass Patienten mit BPS Einschränkungen in beiden Facetten von Empathie zeigen, aber komorbide PTBS, intrusive Symptomatik und sexuelle Traumatisierung in der Vergangenheit mit schlechterer kognitiver Empathie einhergehen. Außerdem ist unter kognitiver Empathie die neuronale Aktivität im linken superior temporal Sulcus/Gyrus (STS/STG) bei BPS Patienten reduziert und mit der Ausprägung ihrer intrusiven Symptomatik assoziiert. Während emotionaler Empathie zeigen Patienten mit BPS im rechten insulären Kortex mehr Aktivität, die mit dem Hautleitwiderstand der BPS Patienten assoziiert ist. Die hier dargestellten Ergebnisse unterstützen ein Bild von BPS als eine Störung der emotionalen und kognitiven Empathie. Eine komorbid diagnostizierte PTBS scheint sich dabei zusätzlich verschlechternd auf die Fähigkeit zur kognitiven Empathie auszuwirken. Die veränderte Funktion von STS/STG und Insula könnte einen pathophysiologischen Vermittlungsmechanismus auf neuronaler Ebene für BPS darstellen, dabei scheinen die intrusiver Symptomatik und dem Grad der Erregung der Patienten eine wesentliche Rolle zu spielen. / Borderline personality disorder (BPD) is a severe psychiatric malfunction, which involves deficits in emotion regulation and interpersonal relationships. Especially the interpersonal problems are seen as a core feature in BPD, even if there is only weak empirical evidence. Furthermore, the current results on behavioral and functional alterations of patients with BPD are biased by the high rate of comorbidity with posttraumatic stress disorder (PTSD). The multidimensional concept of empathy seems to be an eligible framework for the interpersonal problems of patients with BPD. Hence, the present work focuses on the identification of behavioral and neural correlates of cognitive (i.e., social cognition) and emotional (i.e., empathic concern) empathy in patients with BPD. Moreover the influence of comorbidities (e.g., PTSD) on the behavioral and neural alterations of patients with BPD was explored. Patients with BPD showed impairments in both facets of empathy, but comorbid PTSD, intrusive symptoms, and history of sexual trauma were only associated with outcomes in cognitive empathy. In this condition the brain responses were significantly reduced in BPD patients compared to controls in the left superior temporal sulcus and gyrus (STS/STG), where this reduction was associated with levels of intrusive symptomatology in the BPD group. During emotional empathy, patients with BPD exhibited greater brain activation than controls in the right middle insular cortex, a response that was associated with skin conductance responses in the patients. Thus, these findings support a conceptualization of BPD as involving deficits in emotional as well as in cognitive empathy. A comorbid PTSD seems to impair the cognitive empathic outcome additionally. Findings at the neural level indicate that altered functioning of the STS/STG and insula represents pathophysiological mediators for BPD, with an important role for intrusive symptomatology and levels of arousal.

Submitted by Fabricia Fialho Reginato (fabriciar) on 2015-08-28T22:49:03Z No. of bitstreams: 1 RenataZancan.pdf: 353007 bytes, checksum: 31a58b0044f4158aacaf13e5e91683cb (MD5) / Made available in DSpace on 2015-08-28T22:49:03Z (GMT). No. of bitstreams: 1 RenataZancan.pdf: 353007 bytes, checksum: 31a58b0044f4158aacaf13e5e91683cb (MD5) Previous issue date: 2013-02 / Nenhuma / O câncer infantil é um conjunto de doenças caracterizadas pela proliferação descontrolada de células anormais. Apesar dos avanços da ciência e da medicina, fazendo com que a taxa de sobrevida chegue em média a 80%, a doença ainda é considerada ameaçadora e os tratamentos são dolorosos e invasivos. Esta experiência pode acarretar consequências psicológicas, dentre elas, o Transtorno de Estresse Pós-traumático (TEPT) ou a presença de sintomatologia do mesmo. Dessa forma, o objetivo dessa dissertação foi investigar a presença de TEPT em jovens sobreviventes de câncer infantil através de dois estudos, um de revisão sistemática e outro empírico. O estudo de revisão sistemática, apresentado na sessão 1, buscou investigar a presença e a prevalência de sintomas de TEPT em sobreviventes de câncer infantil, fatores associados ao transtorno e implicações clínicas. Identificaram-se índices de sintomas de TEPT mais altos nos sobreviventes quando comparados à população em geral. Variáveis como idade, idade no diagnóstico, sintomas de TEPT nos pais e crenças sobre saúde e doença foram associadas ao TEPT. Destacou-se a necessidade de intervenções clínicas específicas para esta população. O estudo empírico, apresentado na sessão 2, foi realizado com 65 adultos e adolescentes, com idade média de 19 anos, que haviam concluído o tratamento há pelo menos um ano em um hospital público de Porto Alegre. O principal objetivo foi investigar a presença de sintomas de estresse pós-traumático e sua relação com a percepção sobre a doença nesses pacientes sobreviventes. Examinou-se também a relação dos sintomas de TEPT com variáveis clínicas e sociodemográficas. Foram aplicados os questionários IPQR-H – Revised Illness Perception Questionaire for Healthy People , para avaliar a percepção sobre a doença, o PCL-C- PTSK Checklist – Civilian Version e SPTSS-Screen for Post -traumatic stress symptoms, para transtorno de estresse pós-traumático e um questionário de dados clínicos e sociodemográficos. Os índices de sintomatologia de TEPT variaram de 9,2% a 18,5% na amostra, não havendo diferenças significativas entre homens e mulheres. Correlações significativas foram encontradas entre sintomas de TEPT e algumas dimensões da percepção sobre a doença. Não foram encontradas associações significativas entre variáveis clínicas e sociodemográficas e sintomas de TEPT. A percepção sobre a doença foi preditora de sintomatologia de TEPT em sobreviventes de câncer infantil. Assim, identificou-se que a percepção sobre a doença deve ser investigada em sobreviventes de câncer infantil para atuar na prevenção e no tratamento de sintomas de TEPT nesses pacientes. Destaca-se a importância do acompanhamento psicológico durante todo o tratamento e após o término do tratamento, durante o período necessário para readaptação desses pacientes a vida social. / Childhood cancer is a group of diseases characterized by uncontrolled proliferation of abnormal cells. Despite advances in science and medicine, making the survival rate reaches 80% on average, the disease is still considered threatening, and the treatments are painful and invasive. This experience can lead to psychological consequences, among them Post Traumatic Stress Disorder (PTSD) or the presence of its symptoms. Thus, the aim of this thesis was to investigate the presence of PTSD symptoms in young survivors of childhood cancer through two studies, one systematic review and one empirical. The systematic review study, presented in session 1, attempted to investigate the presence and prevalence of PTSD symptoms in childhood cancer survivors, factors associated with the disorder and clinical implications. Higher indices of PTSD symptoms were identified when compared to general population. Variables as age, age at diagnosis, PTSD symptoms in parents and beliefs about health and illness were associated with PTSD. We pointed out the need for specific clinical interventions for this population. The empirical study presented in session 2 was conducted with 65 adults and adolescents with the mean age of 19, who had completed the treatment, at least one year before, in a public hospital in Porto Alegre. The main objective was to investigate the presence of PTSD symptoms and its relation to illness perception in these survivor patients. It also examined the relationship between the PTSD symptoms and the clinical and sociodemographic variables. Questionnaires were IPQR-H – Revised Illnes Perception Questionnaire for Healthy People, to assess the perception of the disease, the PCL-C-PTSK checklist – Civilian Version and SPTSS- Screen for Post-Traumatic Stress Symptoms for Posttraumatic Stress Disorder and a questionnaire of clinical and sociodemographic date. The rates of PTSD symptoms ranged 9.2% to 18.5% in the sample, with no significant differences between men and women. Significant correlations were found between PTSD symptoms and some dimensions of illness perception. No significant associations were found between clinical and sociodemographic variables and PTSD symptoms. The illness perception was a predictor of PTSD symptoms in survivors of childhood cancer. Thus, we identified that the illness perception should be investigated in childhood cancer survivors in order to act in the prevention and treatment of PTSD symptoms in these patients. We highlight the importance of psychological counseling throughout the treatment and after the treatment during the period required for rehabilitation of these patients social life.

Made available in DSpace on 2016-04-28T20:39:15Z (GMT). No. of bitstreams: 1 FlaviaSilva.pdf: 1342298 bytes, checksum: 3f1bb82d3d44eb1bf3d06e8318041238 (MD5) Previous issue date: 2006-06-02 / This research is the result of the master s degree dissertation in Clinical Psychology in the Psychosomatic Department and Hospital Psychology of PUC-SP, with theorical reference to the psychoanalitic theory. The study had, as a first objective, the literature revision of the posttraumatic stress disorder (PTSD) in children; as second, the literature revision in the psychodinamic of the trauma experience in the psychoanalitic clinic, and as the third objective, the apprehension of the posttraumatic stress disorder (PTSD) clinical presentation with the psychodinamic of the trauma experience. For the first revision, the data bases Pubmed, Medline, Lilacs and Pilots were used. For the second, it was used database entailed Psique to the library of the São Paulo s Institute of the Brazilian Psychoanalysis Society. The study includes the posttraumatic stress disorder (PTSD) aspects in children with an illness or a potentially serious, acute or chronic, medical condition and studies about the trauma subjective experience in the psychoanalitic theory involving the sick children. The studies with children excluded those who were victims of automobile trauma. The apprehension of the PTSD from the psychodinamic theory was based on elements of S. Freud, S. Ferenczi and D. W. Winnicott s theories. The results, as well as the discussion, had demonstrated a Brazilian publication scarcity in the area. They had evidenced the joint and apprehension of the PTSD with the trauma psychoanalitic psychodinamic. It was possible to verify the serious disease traumatic potential in infancy and the damages that it can cause in the biological, psychic and social development, when the child cannot give a meaning to her experiences in her representation system. Steady care and social support can act as protection factors, favoring a growth posttraumatic stress situation. Finally, it has been considered that the health professionals whom directly deal with these children have an important paper to brighten up the stressing effects of these experiences, as well as the psychoanalitic psycotherapy can offer a accompaniment for the child in the confrontation with the irrepresentable. / Esta pesquisa é resultado da dissertação de mestrado em Psicologia Clínica no Núcleo de Psicossomática e Psicologia Hospitalar da PUC-SP, com referencial na teoria psicanalítica. O estudo teve como um primeiro objetivo a revisão de literatura do transtorno de estresse pós-traumático (TETP) na criança; como segundo, a revisão de literatura sobre a psicodinâmica da experiência do trauma na clínica psicanalítica e como terceiro objetivo, a compreensão da apresentação clínica do transtorno de estresse pós-traumático (TETP) com a psicodinâmica da experiência do trauma. Para primeira revisão utilizou-se os bancos de dados Pubmed, Medline, Lilacs e Pilots. Para a segunda, utilizou-se a base de dados Psique vinculada à biblioteca do Instituto da Sociedade Brasileira de Psicanálise de São Paulo. Foram incluídos no estudo os aspectos do transtorno de estresse pós-traumático (TEPT) na criança portadora de uma doença ou condição médica potencialmente grave, aguda ou crônica e estudos sobre a experiência subjetiva do trauma dentro da teoria psicanalítica envolvendo a criança doente. Foram excluídos estudos sobre crianças vítimas de trauma automobilístico. A compreensão do TEPT a partir da teoria psicodinâmica foi fundamentada em elementos da teoria de S. Freud, S. Ferenczi e D. W. Winnicott. Os resultados, bem como a discussão, demonstraram uma escassez de publicações brasileiras na área. Evidenciaram a fatível articulação e compreensão do TEPT com a psicodinâmica psicanalítica do trauma. Foi possível verificar o potencial traumático da enfermidade grave na infância e os prejuízos que pode causar no desenvolvimento biopsicossocial quando a experiência deixa de ser significada no sistema de representações da criança. Cuidados estáveis e suporte social podem atuar como fatores de proteção favorecendo um crescimento pós-situação traumática. Finalmente, consideramos que os profissionais de saúde que lidam diretamente com essas crianças têm importante papel no sentido de amenizar os efeitos estressógenos dessas vivências, assim como a psicoterapia psicanalítica pode oferecer um acompanhamento para a criança no confronto com o irrepresentável.

O proposito deste estudo e avaliar o impacto psicologico da vivencia hospitalar de individuos que sofrem complicacoes pos-operatoria, partindo do pressuposto de que a intercorrencia agrava o quadro clinico com repercussoes na esfera psiquica destes pacientes. Teoricamente enfoca a evolucao do conceito de trauma na teoria freudiana, partindo do desamparo primordial (hilflosigkeit) ate a nova concepcao de angustia, levando em consideracao o fator economico, a nocao de a posteriori (nachträglichkeit) e a compulsao a repeticao. Com o intuito de ampliar a compreensao do fenomeno, o estudo percorre a etiologia do trauma para outros teoricos: Sandor Ferenczi, sobre o narcisismo da doenca; Donald W. Winnicott, que correlaciona o trauma a vivencia do fracasso do ambiente, a imprevisibilidade, ao excesso de tempo de exposicao a situacao desorganizadora, e a elevacao do nivel de dependencia. A constancia desta situacao leva ao que Maksud Khan nomeou de trauma cumulativo. A hipotese e a de que esta experiencia hospitalar pode promover um trauma psiquico, na medida em que o individuo se ve diante de uma situacao imprevisivel, que pode lhe causar transbordamento emocional pelo estado de desamparo, impotencia e risco da perda de sua integridade fisica -, que inibe uma elaboracao psiquica. Apos a alta hospitalar tais fatores podem, ainda, desencadear efeitos pos-traumaticos, acarretando-lhe, assim, uma dificuldade adaptativa. Para Moty Benyakar isto significa que o evento disruptivo pode promover um vivenciar traumatico dado a magnitude do impacto no psiquismo. Metodologicamente, para melhor compreensao do processo psiquico, faz-se um estudo longitudinal, de seis sujeitos, iniciando enquanto estes se encontram hospitalizados (situacao potencialmente traumatica), tres e seis meses apos a alta hospitalar. Na aplicacao do metodo qualitativo o estudo baseia-se na coleta de dados com entrevistas e na aplicacao reduzida da tecnica projetiva do TAT (Thematic Apperception Test). Pelo metodo quantitativo os pacientes sao submetidos a aplicacao da escala de avaliacao do transtorno de estresse pos-traumatico (CAPS Clinician Administred PTDS Scale). Esta pesquisa foi realizada em Hospital Escola de Universidade Publica, apos a aprovacao do Comite de Etica desta instituicao e do Comite de Etica para Seres Humanos do Instituto de Psicologia da Universidade de Sao Paulo. Atraves dos resultados obtidos na pesquisa pode-se constatar que ha uma relacao direta entre o evento e os seus efeitos no psiquismo. Pelo proprio carater disruptivo da instituicao hospitalar, dos encargos dos problemas de saude e do entorno (familiar, socioeconomico) o individuo vivencia uma vulnerabilidade fisica e psiquica. Contudo constatou-se que a dimensao da repercussao psiquica esta diretamente associada ao quadro clinico dos pesquisados, e ao tempo que ficam expostos a situacao potencialmente traumatica. Sendo este um fator fundamental na incidencia dos sintomas do Transtorno de Estresse Pos-traumatico. Com base neste estudo psicologico das complicacoes pos-operatorias, espera-se possibilitar aos profissionais de saude um novo olhar ao promover sua conscientizacao sobre problemas advindos desta experiencia, nao so aos individuos como, tambem, aos familiares, levantando a possibilidade de, se necessario, recorrerem a uma assistencia psicologica e/ou psiquiatrica / The objective of this study is to assess the psychological impact in subjects who stay in hospital after suffering from post-operative complications, on the assumption that the clinical picture gets worse causing troubles in the psychic area of these patients. Theoretically it focuses the evolution of the concept of trauma according to Freudian theory, since the primordial abandonment (hilflosigkeit) up to the new concept of distress, considering the economical situation, the concept of a posteriori (nachtraglichkeit) and the repetition compulsion. Aiming to offer a deeper understanding of the phenomenon, the study works with the etiology of trauma by other theorists: Sandor Ferenczi, about the narcissism of the disorder; Donald W. Winnicott, who relates the trauma to the experience of the environment failure, the unpredictability, the length of time facing a disordering situation, and the raising in dependence level. The constancy of this situation leads to what Maksud Khan called as cumulative trauma. The hypothesis is that in-hospital experience might provide a psychic trauma in so far as the subject has faced an unpredictable situation that might cause an overflow of emotions feeling abandoned, powerless and at the risk of losing physical integrity -, inhibiting a psychic elaboration. After having been discharged from hospital, such factors might also trigger post traumatic effects, implying into an adapting difficulty. According to Moty Benyakar, the disruptive event might provide a traumatic experience due to the great impact in the psychism. Methodologically for a better understanding of the psychic process, a longitudinal study has been made, with a number x of subjects, starting while they are in hospital (a potentially traumatic situation), from three to six months after they had been discharged from hospital. Applying the qualitative method the study has been based on the data collected through interviews and in the reduced application of the projective technique of TAT ( Thematic Apperception Test). Through the quantitative method the patients have been submitted to the application of the evaluation scale on the post-traumatic stress disorder (CAPS - Clinician Administered PTDS Scale). This research was carried out at the Hospital Escola da Universidade Publica, after the approval of the Comite de Etica ( Ethics Committee) of this institution and the Comite de Etica para Seres Humanos ( Ethics Committee for Human Beings) of the Instituto de Psicologia (Psychology Institute) of Universidade de Sao Paulo (USP). Through the results provided by the research, it was observed that there is a direct relation between the event and the effects in the psychism. For the own disruptive aspect in hospital, the burdens of health disorders and other surroundings ( familiar, socio- economic problems), the subject lives in a physical and psychic vulnerability. However it was pointed out that the dimension of the psychic repercussion is directly linked to the clinical picture of the six subjects who are studied, and the length of time that they have been exposed to the potentially traumatic situation. And this factor is extremely important in the incidence of the symptoms of the Post-Traumatic Stress Disorder. This psychological study of the post- traumatic surgery complications is meant to bring to health professionals much more awareness about the problems that come after this experience, not only for the subjects as well as to the relatives, who should be allowed to require, whenever necessary, some psychological and/or psychiatric treatment

Purpose: Posttraumatic stress disorder (PTSD) affects nearly 10% of the population, a prevalence comparable with that of tinnitus. Similarities between the way PTSD and tinnitus influence auditory behaviors include exaggerated startle responses and decreased loudness tolerance. Tinnitus loudness is often exacerbated by sounds that trigger PTSD-related anxiety. This report addresses physical and psychological relations between PTSD and tinnitus. Method: A chart review of veterans seen over a 4-year period for tinnitus services was conducted. Case history and self-assessments of tinnitus handicap were examined in all patients. A review of the literature related to triggers and effects of PTSD was conducted to explore potential consequences related to the presence of PTSD in the Veterans Affairs Medical Center (VAMC) tinnitus population. Results: Chart review confirmed that 34% of the first 300 patients enrolled in the VAMC Tinnitus Clinic also carried a diagnosis of PTSD. Patient reports citing tinnitus severity, suddenness of tinnitus onset, sound-tolerance problems, and sound-triggered exacerbation of tinnitus were more common for patients with a PTSD diagnosis than patients with tinnitus only. Conclusions: Several neural mechanisms linked to both tinnitus and PTSD affect auditory behaviors. Audiologists should be aware that patients with tinnitus and PTSD will require test protocols and referrals that address these powerful responses.