Posttraumatic stress disorder (PTSD) is an anxiety disorder that may result from an exposure to a severely traumatic life-event. It is characterised by a delayed onset of psychological and physical symptoms including re-experiencing the event, avoidance of reminders associated with the trauma, increased autonomic arousal and distinct memory deficits. This disorder is also characterised by a maladaptive hypothalamic-pituitary-adrenal (HPA)-axis response and altered monoamine concentrations in the hippocampus and pre-frontal cortex. The Time Dependent Sensitization (TDS) model is a putative animal model of PTSD that is based on the concept of repeated trauma, using three acute stressors (TS) of intense severity followed by a mild situational reminder (RS) on day 7 subsequent to the acute stressors. The aims of this study were to determine if the Triple Stressor (TS) induces stress and if the situational reminder (RS) is necessary for the maintenance of the stress response over time and whether these two stress responses are qualitatively and quantitively different. This was done to further validate the TDS model and to characterize the development and progression of the stress-related pathology of PTSD. Methods used were High Performance Liquid Chromatography (HPLC) with electrochemical detection (biochemical correlates) for quantifying the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) concentrations in the hippocampus and pre-frontal cortex (PFC); radio immuno assay (RIA) for the determination of plasma corticosterone concentrations (neuroendocrine parameter) and the use of the Elevated Plus Maze (EPM) to detect anxiety-like behaviour (behavioural analyses). The study was subdivided into an Acute and Re-Stress study (n = 10). In the Acute Study rats were exposed to TS as the only stressor. Group 1 was sacrificed immediately after TS, Group 2 was sacrificed 3 days post TS and Group 3 on day 7 post TS. In the Re-Stress Study both TS and RS were used as stressors. Group 4 was sacrificed immediately after the situational reminder, Group 5 was sacrificed 3 days post RS and Group 6 on day 7 post RS. A group of unstressed rats were used as Control. The results of this study found corticosterone concentrations elevated immediately after the TS (p<0.05). Exposure to the RS resulted in a profound hypocortisolism (p<0.05). These results indicate a possible disturbance in the regulation of the HPA-axis, which manifests as an enhanced negative feed-back upon re-introduction of the stressful situation. Changes in MA concentrations were evident. Although no definite fixed trend is apparent in this study, it is evident that the TDS model does induce monoamine dysregulation. Hippocampal NA. DA and 5-HT concentrations were noted to be elevated on day 7 post TS (p<0.05). On day 7 post RS only hippocampal 5HT was decreased significantly (p<0.05). Behavioural analyses indicate that stress related anxiety was not sustained after the TS but 7 days after the exposure to the RS rats were most anxious (p<0.05). The results confirm that the TDS model does induce PTSD-like symptoms in rats and that the situational reminder (RS) is necessary for the maintenance of the stress response. This model may be useful in the investigation of future experimental pharmacological interventions in the management of PTSD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

Posttraumatic stress disorder (PTSD) is an anxiety disorder that may result from an exposure to a severely traumatic life-event. It is characterised by a delayed onset of psychological and physical symptoms including re-experiencing the event, avoidance of reminders associated with the trauma, increased autonomic arousal and distinct memory deficits. This disorder is also characterised by a maladaptive hypothalamic-pituitary-adrenal (HPA)-axis response and altered monoamine concentrations in the hippocampus and pre-frontal cortex. The Time Dependent Sensitization (TDS) model is a putative animal model of PTSD that is based on the concept of repeated trauma, using three acute stressors (TS) of intense severity followed by a mild situational reminder (RS) on day 7 subsequent to the acute stressors. The aims of this study were to determine if the Triple Stressor (TS) induces stress and if the situational reminder (RS) is necessary for the maintenance of the stress response over time and whether these two stress responses are qualitatively and quantitively different. This was done to further validate the TDS model and to characterize the development and progression of the stress-related pathology of PTSD. Methods used were High Performance Liquid Chromatography (HPLC) with electrochemical detection (biochemical correlates) for quantifying the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) concentrations in the hippocampus and pre-frontal cortex (PFC); radio immuno assay (RIA) for the determination of plasma corticosterone concentrations (neuroendocrine parameter) and the use of the Elevated Plus Maze (EPM) to detect anxiety-like behaviour (behavioural analyses). The study was subdivided into an Acute and Re-Stress study (n = 10). In the Acute Study rats were exposed to TS as the only stressor. Group 1 was sacrificed immediately after TS, Group 2 was sacrificed 3 days post TS and Group 3 on day 7 post TS. In the Re-Stress Study both TS and RS were used as stressors. Group 4 was sacrificed immediately after the situational reminder, Group 5 was sacrificed 3 days post RS and Group 6 on day 7 post RS. A group of unstressed rats were used as Control. The results of this study found corticosterone concentrations elevated immediately after the TS (p<0.05). Exposure to the RS resulted in a profound hypocortisolism (p<0.05). These results indicate a possible disturbance in the regulation of the HPA-axis, which manifests as an enhanced negative feed-back upon re-introduction of the stressful situation. Changes in MA concentrations were evident. Although no definite fixed trend is apparent in this study, it is evident that the TDS model does induce monoamine dysregulation. Hippocampal NA. DA and 5-HT concentrations were noted to be elevated on day 7 post TS (p<0.05). On day 7 post RS only hippocampal 5HT was decreased significantly (p<0.05). Behavioural analyses indicate that stress related anxiety was not sustained after the TS but 7 days after the exposure to the RS rats were most anxious (p<0.05). The results confirm that the TDS model does induce PTSD-like symptoms in rats and that the situational reminder (RS) is necessary for the maintenance of the stress response. This model may be useful in the investigation of future experimental pharmacological interventions in the management of PTSD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

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

Introduction: Recent developments in the study of trauma responses have shown how some people may experience positive and life altering changes following traumatic life events which have been described as posttraumatic growth. Research is beginning to examine the role of trauma treatments in the facilitation of posttraumatic growth. Aim: This study sets out to explore participants’ experiences of posttraumatic growth during Eye Movement Desensitization and Reprocessing therapy, and the role of the therapeutic relationship in facilitating posttraumatic growth. Method: Semi-structured interviews were carried out with participants to examine their phenomenological experiences. Methodology: Interpretative Phenomenological Analysis was employed to consider emergent meanings and themes within a hermeneutic circle of interpretation. Participants: Seven participants were interviewed who had received Eye Movement Desensitization and Reprocessing therapy within National Health Service primary care psychological therapy services for posttraumatic stress disorder. Findings: Four superordinate themes emerged from the analysis of the participant accounts including: (i) Safe and secure; (ii) Taking back control; (iii) Reconstructing the self; and (iv) Journeying beyond trauma to the future. Conclusions: Person-centred conditions and client-therapist attachment were important elements of the therapeutic relationship which provided participants with the safety, trust, and relational depth necessary for the facilitation of experiences of posttraumatic growth during Eye Movement Desensitization and Reprocessing therapy. Implications: The findings emphasise the importance of a clinical focus on the quality of the therapeutic relationship as a facilitative therapeutic environment allowing affective-cognitive processing and the emergence of posttraumatic growth.

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

Moral injury (MI) is associated with severe blame-related emotion and the development of psychopathology including posttraumatic stress disorder (PTSD). Little is known about how MI events are neurally processed when PTSD is comorbid, limiting the development of tailored interventions. Thus, this thesis sought to provide a novel, multi-method examination of the biological underpinnings of moral injury and relevant behavioural correlates. Study one provides the first investigation into the neural activation patterns elicited during MI event recall in military members and public safety personnel with PTSD, relative to MI-exposed civilian controls. In PTSD, emotional processing is challenged by heightened sensory information. Here, we provide evidence of heightened viscerosensory information processing (i.e. internal gnawing or gastrointestinal constriction related to blame-based emotion) during MI event recall, which appears to exert a strong influence over cortical regions facilitating moral cognitive processes including emotion regulation, autobiographical memory integration, and social cognition. Overwhelming visceral sensations can elicit defensive behaviour including tonic immobility (TI), a defensive response that facilitates viscerosensory dampening. Interestingly, more severe negative alterations in cognition and mood were associated with viscerosensory dampening in our PTSD group, pointing towards a compensatory pattern of emotional numbing. Studies two and three explore two posttraumatic symptoms consistent with emotional numbing: alexithymia and posttraumatic TI. In study two, we explore posttraumatic TI as a survival-based dissociative response and test a new measure of posttraumatic TI. In study three, we provide evidence that alexithymia is associated with an altered (muted) pattern of emotion-specific bodily sensation. This thesis provides a framework for embodied MI event processing in PTSD and highlights the importance of assessing the somatic experience of MI and screening for TI responses and emotional numbing as part of PTSD symptomatology. The evidence presented here suggests sensorimotor-based approaches and bottom-up regulatory strategies may be useful adjuncts to MI event processing. / Dissertation / Doctor of Philosophy (PhD) / Moral injury (MI) is a psychosocial-spiritual injury that can occur when deeply held values are violated either by oneself or a trusted other; it produces considerable pain and social alienation. MI has been linked to suicide and the development of posttraumatic stress disorder (PTSD), a mental health condition associated with distressing symptoms and reduced functioning in important areas of life, including social relationships. This thesis focuses on how MI events are processed by military members and public safety personnel, who are both at risk for MI and PTSD. We investigate how shame is experienced in the brain and body, and explore how intensified visceral sensations may become overwhelming (e.g., pit in stomach, vomiting) prompting emotional numbing or difficulties remaining embodied in the present moment (e.g., zoning out, freezing up). By understanding MI event processing when PTSD is present, we hope to gain insight into more effective treatments for these individuals.

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Mobile technology is increasingly leveraged for mental health interventions, with users expressing overall satisfaction and finding the apps helpful and user-friendly. While the apps offer diverse features for symptom management, self-help, and treatment support, evidence regarding their effectiveness remains limited, suggesting a need for further research. Usability, engagement, and tailoring to user preferences emerge as critical factors, emphasizing the importance of customization for different populations. This research presented a systematic literature review aimed at evaluating studies specifically focusing on post-traumatic stress disorder (PTSD) apps, with a subsequent quality assessment using the MARS scale. Additionally, the research involves an in-depth analysis of user reviews for these PTSD apps through thematic, and path analysis. The technology acceptance model (TAM) model serves as the framework for path analysis, and the performance of VADER, Flair, and TextBlob is evaluated. Sentiment analysis is then employed to explore relationships among TAM model factors and additional factors derived from the systematic literature review and thematic analysis. In conclusion, this dissertation contributes to the understanding of PTSD apps, their usability, and their potential for mental health support. It underscores the need for further research, customization, and ongoing collaboration to optimize the effectiveness of these applications in managing PTSD symptoms and supporting individuals in their mental health journey.

Le blocage de la reconsolidation mnésique sous propranolol est utilisé pour traiter le trouble de stress post-traumatique (TSPT) et le trouble de l’adaptation (TA), montrant une réduction significative des symptômes auto-rapportés chez environ 70% des patients. La présente étude d’archive a examiné l’impact de la dose de propranolol sur l’efficacité de cette thérapie. Les données de quatre essais cliniques ont été regroupées. Un modèle mixte a été utilisé pour comparer les symptômes de stress entre deux groupes (dose de 1,67 mg/kg vs 1 mg/kg) sur la durée normale d’un traitement, soit 6 semaines. Les résultats ont indiqué que, comparativement au groupe (n = 61) ayant reçu la dose la plus élevée, celui (n = 76) ayant reçu une dose moins élevée a présenté une amélioration plus importante des symptômes à travers le temps, révélant ainsi un effet d'interaction, F(6, 740) = 8.54, p < .001. L’analyse secondaire examinant la corrélation dose-effet (dose absolue, p. ex., 40 mg, 50 mg, 60 mg, etc.) à travers les séances de traitement au sein de chacun des deux groupes n’a pas mis en lumière un effet de dose, ce qui était attendu. Des études prospectives seront nécessaires pour clarifier la relation dose-effet dans le cadre de cette thérapie. / Blocking memory reconsolidation with propranolol is used to treat post-traumatic stress disorder (PTSD) and adjustment disorder (AD), showing a significant reduction in self-reported symptoms in about 70% of patients. This archival study examined the impact of propranolol dosage on the efficacy of this therapy. Data from four clinical trials were pooled. Linear Mixed Model was used to compare stress symptoms between two groups (1.67 mg/kg vs. 1 mg/kg) over the typical 6-week treatment period. The results indicated that, compared to the group (n = 61) receiving the higher dosage, the group (n = 76) receiving the lower dosage showed a greater improvement in symptoms over time, revealing an interaction effect, F(6, 740) = 8.54, p < .001. A secondary analysis examining the dose-response correlation (absolute dose, e.g., 40 mg, 50 mg, 60 mg, etc.) over treatment sessions within each of the two groups did not reveal a dose effect, as expected. Prospective studies are needed to clarify the dose-response relationship in this therapy.

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