L’objectif de cette thèse est de repérer les mécanismes psychopathologiques inconscients susceptibles de conduire des sujets gays à prendre des risques par rapport au VIH/sida. D’un point de vue épidémiologique, les homosexuels masculins constituent en effet la « population » la plus touchée par cette épidémie en France. Or, les études de psychologie comportementale et de sociologie constructionniste déjà menées sur ce sujet sont limitées dans leur analysepar des présupposés rationalistes et des méthodologies directives. En partenariat avec des associations de lutte contre le sida, nous avons mené des entretiens basés sur l’association libre, le transfert, et analysés à l’aune du signifiant selon lesenseignements de Freud et de Lacan. S’en dégage un savoir inédit, propre à chaque sujet, et qui traverse l’ensemble des cas. Le moment de bascule dans le risque intervient comme une tentative de séparation par rapport à une problématiqueinconsciente dans laquelle le sujet se vit aliéné. Cette problématique a pour fondement structural le rejet du phallus du don dans l’Autre, auquel le sujet se vit réduit lors de ruptures amoureuses ou quand la réalisation de soi dans une pratiqueartistique devient impossible. Dans ces contextes, le sida fait l’objet d’une fétichisation, susceptible de mortifier davantage encore le sujet. Mais en lui redonnant la parole là où elle lui a manqué dans l’acte, des entretiens orientés par lapsychanalyse sont à mêmes de le détourner du risque. Par rapport à ces cas de structure fétichiste, des cas de psychose sont enfin discutés, qui permettent d’envisager une clinique continuiste des suppléances au manque dans l’Autre / The objective of this dissertation is to identify unconscious psychopathological mechanisms adequate to induce risk behaviour related to HIV/Aids in gay men. Namely, seen from an epidemiological perspective, gay males compose the section of the population most affected by this epidemic. Existing studies in behavioral psychology and constructivist sociology dealing with this question are limited in their analysis by rationalist assumptions and their directiveapproach. In cooperation with associations fighting against Aids, we carried out interviews based on free association and transference and analysed them following the teachings of Freud and Lacan. An unprecedented knowledge is produced byeach person for his individual case and at the same time pervades the totality of the cases. The moment of taking a risk occurs in an attempt of detachment related to an unconscious problem in which the person is alienated from himself. This problem is structurally based on the rejection of the phallus of giving in the Other, to which the person feels reduced after a breakup or when the self-realization by means of artistic activity fails. In this context, Aids becomes an object of fetishisation”, leading to further mortification of the person. By giving back the words where they were lacking in the act, interviews based on psychoanalysis are able to change a person’s risk behaviour. Finally, we will discuss these cases of fetishist structure in comparison with cases of psychosis, which will enable us to make out common traits in theapproach to emptiness in the Other

This is a thesis on madness and moments and what happens in between. I invite the reader into the world of a post-psychotic woman living within and without a Kuwaiti culture. As a fragmented and traumatised researcher I use my chaotic and dismembered writing as a narrative quilt creating a layered account of conversations and stories, in other words, “moments of meeting”. Moments that make us, define us and continue to create knowledge. In those moments, I dialogue with myself, with other people representing different cultures as well as the different “messy” theorists I draw on in my work. The messy theorists include writers such as Alec Grant, Sophie Tamas, Helene Cixous and Susanne Gannon. Through the creative freedom afforded me by their theories I begin to explore my chaotic psychic landscape. Those explorations are, what I call in this thesis, process inputs as they are also reflections of my personal process in writing this autoethnography. They exist alongside the moments of meeting to create snapshots of my experiences from different perspectives at different times. In this work, as a bipolar Kuwaiti woman, I have a dual purpose, where I give voice to my lived experience of a severe mental illness highlighting my struggle with narrative coherence as well as to provide a Kuwaiti I-account detailing my experience of being “othered” as a result of my “mad episodes”. I hope to, in the process, provide people with severe mental illnesses, Kuwaiti women and members of marginilised communities who have been forced out of the cultural scripts or master narratives of their country with constitutive narrative resources and alternative story lines that they can draw on in their journey towards “a more functional state” in the case of severe mental illness and the creation of a dialogue with people who are unable to, for cultural reasons communicate about their experiences.

Research demonstrating the positive effects of Mindfulness-Based Interventions (MBIs) has led to a growing interest in the use of mindfulness across a range of populations and psychological difficulties. This thesis explores the feasibility and benefits of mindfulness in relation to self-esteem and psychosis. Paper one is a systematic review exploring the relationship between mindfulness and self-esteem. The review had two main aims: to synthesise and critically appraise studies exploring the association between mindfulness and self-esteem, and studies investigating the impact of MBIs on self-esteem. Thirty-two studies were identified and quality assessed to guide interpretation of results. All cross-sectional studies found significant positive correlations between dispositional mindfulness and self-esteem, whilst improvements in self-esteem were found in the majority of MBI studies. Despite largely positive findings, the review highlighted the need to interpret these with caution due to methodological weaknesses. Priorities for research were identified, with further investigations needed to assess the impact of mindfulness as an intervention for low self-esteem. Paper two is an empirical paper investigating the feasibility of Mindfulness-Based Cognitive Therapy (MBCT) for psychosis. Sixteen participants, with experience of psychosis, completed an 8-week MBCT group. A repeated measures design was used to explore psychological wellbeing and clinical outcomes following MBCT, including clinical functioning, mindfulness, psychotic symptoms, recovery, beliefs about self, others and voices; and to provide a preliminary exploration of changes in the way a person construes their self, others and their experience of psychosis, following MBCT, using repertory grids. Findings from this feasibility and pilot study were promising, indicating that MBCT groups for psychosis are feasible. Preliminary outcome data highlighted potential areas of change for further investigation in a large scale controlled trial, with possible improvements in participants’ self-reported ability to act with awareness and in recovery, and with some evidence of changes in construing following MBCT. The study demonstrated the feasibility and potential benefits of MBCT groups for people experiencing psychosis, and provided a platform for future research. Paper three is a critical reflection of the papers presented and the research process as a whole. Areas of strengths and weaknesses are highlighted, with an evaluation of the decisions made throughout. The implications for clinical practice are discussed as well as areas for further research.

BACKGROUND: Demand for mental health services, especially for clinical high-risk and early psychosis, has increased, creating a need for new solutions to increase access to and quality of care. Smartphones and mobile technology are potential tools to support coordinated specialty care (CSC) for early psychosis, given their potential to augment the six core roles of care: case management and team leadership, recovery-oriented psychotherapy, medication management, support for employment and education, coordination with primary care services, and family education and support. Such digital tools could enhance patient care and mitigate challenges for CSC. However, the services smartphones are offering specifically for coordinated specialty care and the level of evidence are unknown. OBJECTIVE: This thesis consists of three phases: 1) to review the published literature on smartphone technology to enhance care for patients with prodromal and early course psychosis and schizophrenia, 2) to create technology implementation guidelines for coordinated specialty care programs, and 3) to assess the framework created in phase two by implementing it at diverse sites across the country. METHODS: Phase I involved a systematic literature search conducted on August 16 and 17, 2019 which used PubMed, EMBASE, Web of Sciences, and PsycINFO electronic databases. All eligible studies were reviewed and screened based on inclusion and exclusion criteria. Phase II was guided by the results discovered in phase I and consisted of modifying the Replicating Effective Programs framework to create a CSC focused model. Phase III entailed the implementation of the framework at eight coordinated specialty care programs in the United States. Findings from each visit guide improvements for the framework. RESULTS: The search conducted in phase I uncovered 388 unique results, of which 21 eligible studies on 16 unique app platforms were identified. Feasibility studies showed high user engagement and interest among patients, monitoring studies demonstrated correlations between app assessments and clinical outcomes, and intervention studies indicated that these apps have the potential to advance care. The AACCS framework was developed in phase II which is composed of five stages: 1) Assess (e.g. identifying access to and comfort with technology), 2) Align (e.g. understanding aspects of coordinated specialty care that technology can augment), 3) Connect (e.g. customizing technology to the needs of patients and clinicians), 4) Care (e.g. implementing the digital tools into treatment), and 5) Sustain (e.g. creating sustainable technology-enabled mental health services). As phase III is ongoing, only results from the first few site visits are shared. Site 1, an amalgamation of three distinct programs, showcased that access to technology was not a barrier, however other aspects necessary for successful technology implementation were missing, such as access to high-speed internet and adequate technology training. Although staff members reported low confidence with technology, they all believed in the potential of technology to assist with all six key roles of CSC. CONCLUSION: The published literature on smartphone apps for prodromal and first-episode psychosis is small but is growing exponentially. Although the research results and protocols for app studies do not align well with all key roles of coordinated specialty care, high rates of adoption and feasibility suggest the potential for future efforts. The findings from the literature review guided the creation of the AACCS framework. This framework is intended to assist CSC programs in the identification of clinical targets to be augmented with digital tools. Implementation of the AACCS framework at many sites highlighted a need for digital literacy training for both patients and staff members. Technology has the unique potential to reduce staff workload, support CSC efforts, and expand the reach of early course psychosis care by erasing distance.

Investigation of the adenosine A(2A) receptor on the enhanced rewarding effects of nicotine and dopamine D2 receptor signaling in a novel heritable model of drug abuse vulnerability Seth E. Turney, Loren D. Peeters, Olivia A. Jennings, Liza J. Wills, Russell W. Brown Many years ago, our laboratory along with a collaborator established that neonatal treatment of the dopamine (DA)D2-like receptor agonist quinpirole (NQ) to rats induces an increase in DAD2 receptor sensitivity throughout the animal’s lifetime, which has validity to schizophrenia (SZ) and a number of clinical conditions. These clinical conditions, which include SZ but also bipolar disorder, obsessive-compulsive disorder, panic disorder, and major depression all demonstrate increased drug abuse vulnerability, especially to cigarette smoking. Based on this permanent change in DAD2 sensitivity, we bred NQ-treated male and female rats with their NQ-treated or neonatal saline (NS)-treated counterparts. This F1 generation also demonstrated increases in DAD2 signaling, both behaviorally as well as through DAD2 signaling mechanisms. We have shown both d enhanced behavioral responding to nicotine on the conditioned place preference (CPP) and behavioral sensitization paradigms. These F1 offspring of NQ-treated rats also demonstrated increases of G-protein dependent and G-protein independent DAD2 signaling. Interestingly, the adenosine A(2A) receptor forms a mutual inhibitory heteromer with the DAD2 receptor. Adenosine is a known neuromodulator that can increase or decrease synaptic transmission in the brain, and there exists a hypothesis that adenosine dysfunction is the primary system which is disrupted in SZ which leads to changes in the dopamine and other neurotransmitter systems. The drug CGS 21680, an A(2A) agonist which stimulates the A(2A) receptor, is known to decrease DAD2 signaling and has been shown to block nicotine behavioral sensitization. A major focus in this project is on the adenosine A(2A) receptor as a novel pharmacological treatment target, since it is known that antipsychotic drugs which are often used to treat SZ and these other clinical conditions which have increased DAD2 signaling produce deleterious side effects, and novel medications are needed. Results here revealed that a 0.09 mg/kg dose of CGS 21680 was effective to block enhanced nicotine CPP and changes in DAD2 G-protein independent signaling in F1 generation rats. Interestingly, CGS 21680 did not affect G-protein dependent signaling in F1 generation animals, suggesting that the mechanism through which it is working may not be through the traditional DAD2 signaling mechanism. Future work is designed to analyze underlying mechanisms of this effect.

Multisystem Inflammatory Syndrome in Children (MISC-C) is a systemic inflammatory disorder associated with novel COVID-19. Children diagnosed with COVID-19 typically experience mild viral symptoms, however, in rare instances more severe disease will develop. Current epidemiology states <1% of children diagnosed with COVID will develop complications of MIS-C. Symptoms of MIS-C are varying, but in general include abnormal vital signs (tachycardia, tachypnea), Kawasaki-like symptoms, respiratory distress, cardiac involvement, and shock like symptoms. Abdominal pain, features of acute kidney injury, coagulopathy, and neurologic dysfunction have also been reported. It is currently recommended for children with any combination of the above symptoms to be hospitalized and treated for MIS-C, given the potential for severe consequences. This case presentation aims to highlight the neurologic symptoms that can occur with the diagnosis of MIS-C. Current estimations predict 20% of children with MIS-C will develop more severe central nervous system symptoms. Our patient presented with neuropsychiatric symptoms, which has little documentation in current medical literature. Initial presentation, differential diagnosis, hospital workup, and treatment of disease will be discussed. Our case is a previously healthy 8yo male with past medical history of ADHD. He presented to the Emergency room with chief complaints of fever, confusion, and visual and motor hallucinations 3 weeks after receiving a positive COVID test. Prior to the date of presentation, the patient’s only symptom of COVID 19 was rhinorrhea. ED workup revealed tachycardia, pallor and erythema/swelling of fingers, facial rash, abdominal pain, and leukocytosis. Initial differential diagnosis included sepsis secondary to urinary tract infection versus encephalopathic MIS-C. Labs at presentation showed CRP and D-dimer within normal limits, and treatment for UTI was initiated. For the first few days of hospital stay, patients condition was unchanged and inflammatory marker levels rose. The patient also showed sustained tachycardia, fever, widened pulse pressures, nocturnal incontinence, and one episode of bigeminy. Treatment targeting MIS-C with, IV ceftriaxone, vancomycin, IVIG, methylprednisone, and aspirin was begun. Inflammatory markers subsequently began to downtrend and patients condition began to improve. This case study highlights central nervous system features as a potential primary presenting symptom of MIS-C. Currently, there is little literature on COVID 19 associated psychosis. Further research is needed to assess the underlying potential inflammatory mechanisms responsible for our patient’s visual and motor hallucinations resulting from MIS-C.

Sleep disturbances have been observed across the entire psychosis spectrum. Research has begun to focus on the clinical high risk (CHR) period for psychosis, as the presence of sleep disturbance can be examined separately from the effects of antipsychotic medication and is potentially a risk factor for later psychosis. Several studies have demonstrated a link between sleep disturbance and worsened positive symptoms in CHR individuals. However, sleep disturbance is not unique to the psychosis-spectrum and is well documented in individuals experiencing dissociation. Transdiagnostically, dissociation has been associated with poorer outcomes and reduced treatment response. Despite the established associations between these variables, their respective contributions to positive symptom severity in the CHR period has not yet been characterized. This study examined the separate and combined contributions of sleep quality and dissociation on positive symptom severity in a cross-sectional sample of individuals identified as being at CHR for psychosis. Hierarchical linear regression was conducted to examine the independent and additive influence of sleep quality and dissociation on unusual thought content, suspiciousness, and perceptual abnormalities. Finally, logistic regression was used to determine if sleep quality and dissociation increase odds of a CHR diagnosis. Analyses of indirect effects revealed a significant indirect effect of sleep disturbance on perceptual abnormalities through dissociation in the CHR group. In addition, both sleep disturbance and dissociation significantly contributed to a model predicting to perceptual abnormalities, also in the CHR group. In the total sample, both sleep quality and dissociation significantly increased the odds of a CHR diagnosis. These results suggest that dissociation plays a significant role in the sleep-attenuated positive psychotic symptom relationship in the CHR period, and as a result, could be a modifiable treatment target in these individuals. / Psychology

Puerperal Psychosis is the most severe form of postnatal psychiatric illness, and is a psychiatric emergency. Human-based research to find a means of genetically predicting a woman's risk of puerperal psychosis has so far failed to reliably or reproducibly identify candidate genes or pathways, due to problems common within the field of psychiatric genetics, leading to the proposal of using an animal model in the form of Porcine Maternal Infanticide. In this project, the author has aimed to understand the pathophysiology of PMI using NGS technologies in order to 1) extend the validity of PMI as a model for PP; 2) determine future steps for development of the PMI model; and 3) generate insights into the management of PMI (and by extension PP) via prediction and detection of a puerperal trigger. These aims have been pursued via two experiments. In the first, the author has created RNA-Seq libraries from archival RNA, and then performed differential gene expression analysis. The results indicated that RNA-Seq technologies can be used with archival RNA samples, but using such samples introduces the risk of degradation-based bias. The substantial influence of outliers, confounding factors and sample size on the results prevented reliable identification of candidate genes" but provide concrete guidelines development of the Porcine Maternal Infanticide model. In the second, the author has created MBD-Seq libraries from archival tissue, and then performed differential methylation analysis. The results indicated that it is possible to use MBD-Seq technologies with Sus scrofa brain tissue. Once again, the effect of confounding factors and sample size on the results prevented reliable identification of candidate genes, but provide guidance for development of the Porcine Maternal Infanticide model.

Indiana University-Purdue University Indianapolis (IUPUI) / Aim: Early psychosis has been identified as period during which rapid identification and treatment can lead to significant improvement in clinical and functional outcomes. Despite increased research, no studies have examined early psychosis in Veteran populations. It is unknown whether Veterans differ from non-Veterans at this stage of the disorder, and if the treatments offered to non-Veterans are appropriate to implement in Veteran Affairs Medical Centers. Given differences that appear between Veterans and non-Veterans in chronic psychosis, additional work is necessary to determine the best way to approach specialized treatment for Veterans experiencing early psychosis. Methods: The current study is a secondary analysis of assessment batteries collected at a community-based early intervention program and at a local Veteran Affairs Medical Center. Assessment results were compared for Veterans’ and non-Veterans’ background characteristics, symptoms, and neurocognitive deficits. Results: Significant differences were found between the two samples on age of illness onset, marital status, education level, positive symptoms of psychosis, and neurocognitive functioning. Logistic regression analyses identified age of onset as a potential underlying factor. Conclusions: While some aspects of illness presentation appear similar between Veterans and non-Veterans, there are important differences between these populations. Pre-existing treatment interventions, such as Social Skills Training, cognitive remediation approaches and cognitive behavior therapy for psychosis may be appropriate to implement with Veterans. Others– such as family based interventions or supported employment services – may need to be tailored to maximize the benefit for Veterans.

Background: Attachment theory represents a developmental framework which proposes that early relationships with primary caregivers have an enduring effect on interpersonal relationships, affect regulation and psychological functioning throughout the lifespan. It has been suggested that this occurs via the influence of internal representations regarding the self, others and relationships, which form the basis of an attachment style in adulthood. Attachment has been conceptualised as a constructive theoretical basis from which to consider psychological mechanisms underlying the emotional distress, interpersonal problems and difficulties in affect regulation commonly associated with psychosis. Aims: A systematic literature review was conducted investigating the current research findings regarding adult attachment style in psychosis and clinical correlates of this. An empirical study used a cross sectional design to investigate the role of adult attachment style in emotional recovery in psychosis. It was hypothesised that attachment insecurity would be associated with higher levels of depression and symptom related distress. Interpersonal problems and emotion regulation were also investigated and it was predicted that these variables would mediate the relationship between attachment insecurity and increased emotional distress. Method: Individuals with psychosis (n=70) completed self report measures of adult attachment style, interpersonal problems and emotion regulation. Clinician rated measures of depression and symptom related distress were also completed. Results: The literature review revealed that adult attachment style is of relevance in psychosis as consistent findings of greater attachment insecurity in psychosis compared with non clinical populations have been reported. Adult attachment insecurity has been associated with a number of clinical outcomes in exploratory research. The empirical study found support for hypothesised associations between attachment insecurity and greater emotional distress. Predicted relationships were also supported between attachment insecurity and higher rates of interpersonal problems and more use of expressive suppression as an emotion regulation strategy. Interpersonal problems significantly mediated the relationship between attachment insecurity and emotional distress. The hypothesised mediating role of emotion regulation was not supported. Conclusions: Findings of the empirical study suggest that insecurity in adult attachment style is an important variable in understanding emotional distress in individuals with psychosis and that difficulties in interpersonal functioning, as a mediating factor in this relationship, may represent a useful focus in clinical work.