There is a growing body of literature demonstrating an association between childhood trauma and schizotypy (e.g. Afifi et al. 2011;Myin-Germeys et al. 2011). However, more research is required to build on methodological limitations of previous studies, explore the possible differential effects of specific trauma types and expand the focus from a single contributor (e.g. psychological, biological) by considering the additive/interactive contributors to schizotypal symptomatology. The aim of the thesis was to explore the relationship between a range of childhood traumatic experiences and schizotypy whilst also incorporating several social, psychological and genetic factors underlying these relationships. Participants were recruited as a part of a cross-sectional case-control study conducted in the London Boroughs of Lambeth and Southwark. The thesis covers a subsample of controls (N=212), healthy volunteers, aged 18-64 and residents in the same geographical area. Data were gathered using an in-depth standardised interview regarding childhood abuse (Childhood Experience of Care and Abuse - CECA) and The Structured Interview for Schizotypy – Revised (SIS-R) measuring a range of schizotypal symptoms and signs. The study found a linear association of total trauma and schizotypy (adj. β=.88, p=0.004), with the strongest associations observed for psychological (adj. OR=4.85, p=0.039) and physical abuse (adj. OR=3.56, p=0.003). These particular types of trauma had an especially robust effect on positive schizotypal traits (psychological: adj. OR=3.79, p=0.013; physical abuse: adj. OR=2.32, p=0.042), which are attenuated forms of positive symptoms of schizophrenia (e.g. hallucinations, delusions). Negative beliefs about self/others and depression were the main mediators of these associations. A strong relationship was found for genetic risk of psychosis and increased schizotypy (adj. β=3.41, p=0.015). Other moderators of the childhood trauma - schizotypy association were intrusive life events (adj. β=4.20, p=0.045). This study provides further insights into the association between childhood trauma and schizotypy and gives clues to pathways underlying this association.

This thesis is presented in three parts. Part one is a review of the literature concerning deinstitutionalisation and the move towards psychiatric care in the community. Studies evaluating the outcomes of psychiatric patients discharged from hospital to community services are discussed. Part two presents a qualitative empirical study which explores the experiences of psychiatric patients in a rehabilitation ward, and the views of staff who work there. The understanding of the rehabilitation process is explored as is the impact of reprovision as a result of ward closure. Part three presents a critical appraisal of the empirical paper, reflecting on theoretical and methodological issues that were raised during the research.

Language defects are one of the nuclear features of schizophrenia, and difficulties in semantic memory processing have been considered to be at the core of these deficits. However, the underlying mechanisms of deficits in semantic memory processing and their relationship to the overt symptoms of schizophrenia are still not entirely understood. Furthermore, tools for assessing language deficits in schizophrenia are sparse and the existing ones are based on observations rather than a pathophysiological understanding of these deficits. The first part of this thesis is a literature review aiming to explore the underlying mechanisms of language deficits in schizophrenia. The review focuses on the findings produced by the studies employing event related potential techniques that aim to provide objective measures of pathophysiological mechanisms of language deficits and relate them to overt, behavioural symptoms in schizophrenia. Given the wealth of data produced by these studies, the review focuses on the recent advances in this area of research and discusses the possible directions for the future research. Part two is an empirical paper presenting a validation of the English version of the Schizophrenia Communication Disorder Scale (SCD). SCD is a clinical scale designed to quantify communication deficits in schizophrenia by assessing the underlying deficits of language disorder in schizophrenia, as demonstrated by electrophysiological findings presented in the review paper. Specifically, the SCD measures contextual information processing and theory of mind abilities. The original version was published in French, and we aimed to translate the scale in to English and provide the preliminary findings on the reliability and validity of the English version. Additionally, SCD data for a healthy control sample has been presented for the first time. Part three includes my personal reflections going through the experience of research. It also includes a critical appraisal of the research project.

This thesis comprises three parts: Part 1 is a review of the literature regarding computerised Cognitive Behavioural Therapy (CCBT) for depression and anxiety disorders focussing specifically on its benefits and drawbacks for clients and clinicians. The review finds strong evidence for the effectiveness of CCBT, mixed evidence for the benefits and drawbacks of CCBT and little existing literature on the acceptability to clients, identifying gaps in the literature which could be addressed by future research. Part 2 is an empirical paper of a qualitative study which used focus groups and interviews to explore the views of clients with chronic depression on computerised interventions in general and their specific views of standard Cognitive Behavioural Therapy (CBT) and Compassionate Mind Training (CMT), using the biomedical model of depression for comparison purposes. Using a thematic analysis approach, key themes which emerged from the focus groups and interviews are identified and supplementary quantitative data is provided. The findings highlight some of the perceived benefits and drawbacks of computerised interventions in general and of the CBT, CMT and biomedical models for a chronically depressed group. Part 3 is a critical appraisal of the research process, highlighting methodological and ethical issues which emerged during the course of the study. It also includes personal reflections on the process of carrying out the research.

Volume One of this D.Clin.Psy. thesis is a research project investigating aspects of perseveration in Axis I psychopathology and is comprised of three parts. Part One is a literature review examining the relationship between stuck-inset perseveration and depression. It aims to answer the question of whether a set shifting impairment might be implicated in the maintenance of depression. Part Two is an empirical paper which first outlines the literature relating to set shifting in anorexia nervosa (AN), evaluating the evidence for trait and state explanations of set shifting deficits in AN. Using a non-clinical population exposed to short-term starvation, the study explores the hypothesis that starvation might exacerbate existing tendencies towards rigidity. The results are discussed in relation to previous findings and the limitations are considered alongside the implications for future research and practice. Part Three is a critical appraisal of the research process. It outlines how the area of study came to be selected and includes some personal reflections on the wider research process. In this section some of the limitations of the study are also discussed in greater detail.

Disrupted In Schizophrenia-1 (DISC1) is a key susceptibility gene implicated in schizophrenia. Previous studies have revealed a potential role for DISC1 in kinesin-1 mediated transport, the same motor responsible for powering mitochondrial transport. Mitochondria are highly dynamic organelles that must be correctly transported to neuronal regions with high energy demand such as growth cones and pre and postsynaptic domains. Disruption of mitochondrial transport impairs correct neuronal development, synaptogenesis and synaptic function. This work demonstrates that DISC1 regulates the level of mitochondrial transport in neurons. Furthermore, DISC1 mediated effects on mitochondrial transport are compromised by a disease associated single nucleotide polymorphism in DISC1, demonstrating a novel role for DISC1 is the brain, and suggesting synaptic energy loss as a potential mechanism explaining DISC1’s contribution in disease. Further investigation of the underlying mechanism revealed a key role for the GSK3β signalling pathway in the regulation of DISC1 mediated control of mitochondrial transport. A further disease mechanism of DISC1 is also addressed. DISC1 forms insoluble protein aggregates in vitro and in human post-mortem brain tissue, but the cellular dynamics of these DISC1 aggregates and their effects on neuronal function are unknown. Via characterisation of DISC1 protein aggregates, these findings localise aggregates to the aggresome, demonstrate a compromised exchange between DISC1 in the aggresome and the cytosolic pool and show a loss of functional DISC1 from the cytosol. Finally a pathological effect of DISC1 aggresome formation in neurons is identified, as aggresome containing neurons display disrupted intracellular transport of mitochondria. Findings presented in this work therefore show a functional role of DISC1 in mitochondrial transport, investigate the mechanisms by which DISC1 mediates this, and finally show the existence of aggresomal DISC1 with disruptive effects on neuronal function, therefore suggesting a novel DISC1 based mechanism for the neuronal contribution to schizophrenia.

Salience attribution, the process by which particular stimuli come to selectively grab one’s attention, is heightened towards drug-associated cues in substance users and irrelevant cues in psychosis. In Chapter 1 I review this literature. Despite their theoretical link and the substantial co-morbidity of substance use in psychotic disorders, the extent to which these processes overlap is not well understood. The aim of this thesis was to investigate their relationship. The ability of drug cues to impact on associative learning processes was examined in Chapter 2 using a newly developed task. Overshadowing by drug cues was found alongside smoking-related attentional bias in abstinent smokers but not in satiated smokers or controls. This overshadowing effect is replicated in Chapter 3 among frequent ketamine users and polydrug-using controls. Ketamine users showed elevated psychotic-like symptoms, a reduction in associative blocking and a stronger impact of drug cues on blocking compared to polydrug controls. These results are indicative of a shared disruption of salience attribution in addiction and psychosis, which I investigated in Chapter 4 among smokers with a diagnosis of schizophrenia. Associative blocking was reduced in these individuals compared to control smokers but both groups displayed an absence of blocking towards drug cues. The patient group also showed higher drug-cue attentional bias that correlated with positive psychotic symptoms. In Chapter 5 I examined the role of dopamine in salience attribution in smokers. The dopamine D2/D3 agonist pramipexole (0.5mg) reduced urges to smoke and decreased attentional bias towards smoking-related images relative to monetary images when compared to placebo. In Chapter 6 I discuss the theoretical and clinical implications of these findings. The effects of drug cues on associative learning provide a methodological advance, and these findings offer preliminary support for a link between disruptions of salience attribution in addiction and in psychosis.

The potential relationship between hypovitaminosis D and non-skeletal health outcomes is a growing public health concern. There is suggestion of a relationship between 25-hydroxyvitamin D (25(OH)D) and brain function, with equivocal epidemiological evidence for an association with common mental disorders (CMD) and cognitive function. The aim of the thesis was to investigate the association of 25(OH)D with CMDs and cognitive function in mid-adulthood. Observational and genetic studies were used to gain better insight into the causal nature of the relationship between 25(OH)D and cognitive function. During observational studies, the association of 25(OH)D with CMDs and cognitive function was assessed in the 1958 British birth cohort (1958BC). A genetic study investigated the potential for a gene-environment interaction (GxE) by APOE ε4 on cognitive function using participants from the 1958BC. This GxE study was replicated in an older European cohort. The causal relationship between 25(OH)D and cognitive function was assessed using a Mendelian randomisation (MR) approach in a meta-analyses using participants from nine European cohorts. Using observational data from 1958BC, there was evidence that both low and high 25(OH)D concentrations were associated with increased risk of CMDs and lower memory function. There was also evidence of a GxE interaction for memory function; where increasing 25(OH)D concentrations may be particularly beneficial for those with APOE ε4 genotype. However, results from a MR study provided no evidence for 25(OH)D concentrations acting as a causal factor for cognitive performance in mid- to later-life. Since there was evidence of a non-linear observational association, the MR study may have been underpowered to detect small causal effects at the extremes of the 25(OH)D distribution. Overall, there is some evidence of a potential non-linear association of 25(OH)D with CMDs and cognitive function. However the causal nature of this relationship requires confirmation from large long-term randomised controlled trials.

This thesis presents an investigation into the concept of parental representations. Part one systematically reviews the role of parenting representations within attachment theory, specifically the extent to which they mediate the concordance between parental and infant attachment. Part two details the development and validation of the 10 PDI, an accessible dimensional coding system, of parental representations for the Parent Development Interview (PDI). The development and initial tests of reliability are reported followed by further psychometric evaluation, through examination of inter-rater reliability and validity. Validity is explored via comparison to parent-infant behaviour, and consideration of the family's current social and emotional context. This research project used some of the same participants as two other D.Clin.Psy. theses (Gale, 2008; Woollaston, 2010). Full details of joint thesis contributions are provided in Appendix 1. In the final part of this thesis, I discuss my experiences of and reflections on conducting this investigation, highlighting the merits and limitations of the secondary use of research data.

This thesis focuses on self-stigma in psychosis. The first part, the systematic literature review, examines the theory of self-stigma and distinguishes between two processes described under this term: internalised stigma and stigma expectations. The literature review then focuses on evaluating available measures of internalised stigma and comments on their ability to capture the concept in question. Following this, empirical studies of the impact of internalising stigma on the lives of people with schizophrenia are reviewed. This constitutes a basis for drawing clinical implications and suggesting future research. The empirical part focuses on the second mechanism of self-stigma, stigma expectations. This project builds on the data set collected for three previous D.Clin. Psy projects completed by Agnieszka Gunning (2007), Tristan Morland (2007) and Kate Theodore (2008). This part starts with a summary of findings from the studies on the impact of stigma expectations on people with mental illness. It then describes the research undertaken by the author: a cross-sectional study of stigma expectations in first episode psychosis. The aims of the study were two-fold. First, to establish whether hospitalisation and detention under the Mental Health Act impact on the strength of stigma expectations of individuals with first episode psychosis. Second, to determine whether the strength of stigma expectations impacts on the subjective sense of recovery. The results of the study, its clinical implications and limitations are then discussed. Future directions for research are suggested. The thesis concludes with a critical evaluation of the entire project. The reasons for my interest in the stigma of mental health are presented. Decisions made and difficulties encountered during the project are discussed. An emphasis is placed on an evaluation of the measures used in the empirical study. The appraisal concludes with consideration of ethical issues and the author's reflections on the concept of recovery.