Search

Background: Health Locus of Control (HLoC), and health beliefs in general, have been found to play a role in the way in which people manage their healthcare needs. Increasingly, patients are being encouraged to self-manage a variety of health conditions, including chronic physical health conditions, such as diabetes, and mental health conditions, such as depression and anxiety. However, evidence regarding which factors might be related to response to self-management is limited. HLoC may help to explain why some take well to the self-management of health conditions, or respond to recommended remote therapies, whereas others struggle to implement advised changes. Similarly, attitudes towards eHealth (AteH) may play a role in engagement with specific remote therapies. Aims & Objectives: The current thesis project aims to consolidate the existing research into the relationship between HLoC and diabetes self-management by conducting a systematic review of the literature (chapter 1), before exploring the concept of HLoC and AteH as potential predictors of response to computerised Cognitive Behavioural Therapy (cCBT), as defined by uptake (starting treatment), adherence (extent to which treatment is completed), and clinical outcome (magnitude of symptom reductions) in chapter 2. Methodology: In chapter 1, a systematic review of the literature was conducted across three electronic databases (PsychINFO, Ovid MEDLINE, and Embase) to examine and critically appraise the literature regarding the relationship between HLoC and adherence to diabetes self management. Studies included research investigating diabetes self-management in relation to HLoC. In chapter 2, a longitudinal study with three major time-points was conducted across N=2130 patients accessing cCBT services in Scotland to individually explore predictors of uptake, adherence and clinical outcomes. Results: N=17 studies were identified and critically reviewed using the AXIS tool in chapter 1. Most were deemed to be of good methodological quality, with a small number of exceptions. The review revealed that the majority of studies found evidence to suggest that stronger internal HLoC beliefs were associated with better adherence to diabetes self-management regimens, however inconsistencies were found across certain HLoC domains, and the heterogeneity of predictor and outcome measures posed a challenge to inter-study comparisons. In chapter 2, neither of the healthcare belief-related factors were found to significantly predict uptake in cCBT services, however both HLoC and AteH predicted higher adherence to cCBT, and various HLoC domains predicted magnitude of clinical changes across treatment. Other significant sociodemographic and clinical predictors of adherence and reductions were found and discussed. Conclusions & Clinical Implications: Chapter 1 concluded that stronger internal HLoC beliefs are positively related with adherence to diabetes self-management regimens, which may improve health outcomes for those self-managing diabetes. However, further research is needed to apply causality to this model. Chapter 2 demonstrated interesting insights into the theoretical factors predicting response to cCBT, which may help inform clinicians in making referrals to the service.

Objective Compassion Focussed Therapy (CFT) was initially developed to treat people with high levels of shame proneness and self-criticism. In CFT, shame is conceptualised as transdiagnostic in psychological distress. The prevalence of psychological distress (including shame) in people living with long-term physical health conditions (LTCs) is well evidenced. There is interest in the use of compassion-focussed interventions for people with LTC's and initial evidence that they can reduce distress and increase self-management behaviours. The presented systematic review explores the current evidence for illness-related shame (IRS) across physical health populations and identifies associated psychosocial factors. The empirical paper investigates the process of change for individuals with various LTCs during a CFT group intervention. Methods Three key databases were searched to identify studies with a measure of illness-related shame (IRS). Papers that met the inclusion criteria were quality assessed and results synthesised to provide narrative summary. A multiple baseline, single case experimental design was used to track changes in compassion, illness cognitions, self-efficacy, social functioning and psychological wellbeing, with daily and weekly measures, over a ten-session structured CFT intervention. Results Results of the review indicated illness-related shame has been tested in a small but diverse number of health conditions and is prevalent in all conditions studied. Associated factors were heterogenous however, the presence of IRS was most commonly associated with reduced wellbeing, increased anxiety and depression, and cognitive fusion. In the CFT group, improved self-compassion was reported across all individuals. Changes on measures related to psychological adjustment were not consistent across individuals. The process of change was gradual, with quantifiable change most commonly demonstrated within the last four sessions of the group. Conclusions IRS is present across a range of LTC groups. Further research is needed to identify differences in the prevalence between LTC populations and clarify the role of IRS as a target for psychological intervention. A CFT group for various and multiple health conditions was effective in producing changes in self-compassion. A clearer understanding of the link between compassion and adjustment to illness is sought to inform changes to intervention or measurement, in order to produce and demonstrate therapeutic change.

This thesis is derived from my own experience that: When I am sane, I am an atheist, but when I am Mad, I am driven by the Hand of God. From this paradoxical position I hypothesise a non-binary Intersection of Madness, Mental Disorder and Acute Religious Experiences. To establish and develop this Intersection I explore the way Madness, Mental Disorder and Acute Religious Experiences have been constructed and how they do and do not construct their referent realities. I explore the interrelation of these ideas showing how these have been addressed, but also remain undertheorised in the Academic disciplines of Psychiatry and Religious Studies. This thesis draws on my experiences but also an extensive bibliography of over six hundred texts split evenly between the sciences and the humanities. I introduce three innovations: 1.) Mad Studies: This approach privileges the voices of those who have experience of Madness. By applying this approach to both Psychiatry and Religious Studies for the first time, traditional models of understanding can be redescribed. 2.) Acute Religious Experiences: I conceptualise these as a distinct category which is competent to address species wide behaviours, in the same way that the categories of ritual or worship are not limited by particular instances. I propose that Acute Religious Experiences as a category is competent to address the full diversity of instances of extreme experiences articulated by humans in ‘religious’ terms. 3.) Disruption: DSM-5 (APA 2013), the dominant psychiatric text, introduces Disruption as a new approach to cultural relativism. I theorise Disruption as a placeholder for the Intersection of Madness, Mental Illness and Acute Religious Experiences. The work of Part II is to develop and establish my theoretical approach. I draw on historical understandings only insofar as they provide context and expose the antecedents on which contemporary understandings of these terms have been constructed. The concern of this thesis is always with the existential states of Disruption and developing my argument that understanding these at the Intersection of Madness, Mental Disorder and Acute Religious Experiences provides new insight and understanding. Part III sets out three very different applications, based on the previous work of theory development: 1.) A critique of contemporary psychiatric research into Religion from a Mad Studies point of view. 2.) An Autoethnographic account of one of my own experiences of Disruption in South India in 1985 and 3.) A radical re-description of the life of the Historical Jesus which becomes possible as a result of my Mad Studies point of view. As the result of the work of this thesis I am able to demonstrate that the non-binary Intersection of Madness, Mental Illness and Acute Religious Experiences provides immediate advantages and also new directions for the Academic disciplines of Psychiatry and Religious Studies and these are set out in my conclusions.

Background. Cognitive Behavioural Analysis System of Psychotherapy (CBASP) has been developed to treat individuals affected by persistent depressive disorder (PDD). There is a growing number of empirical studies to suggest that CBASP is effective in treating chronically depressed population. Taking into account these findings as well as the chronic and debilitating nature of persistent depression, it can be invaluable, when planning treatment, to understand the factors contributing to and maintaining this condition, as well as mechanisms of change involved in CBASP. Purpose. A systematic review aimed to establish the quality of evidence indicating the effectiveness of CBASP when addressing difficulties with interpersonal functioning which are believed to be causing and maintaining depressive symptoms according to the theory of persistent depression developed by McCullough (2000). McCullough hypothesised that childhood trauma leads to an impairment in the cognitive-emotional development, which then leads to interpersonal difficulties that result in depressive symptoms. An empirical study aimed to identify the strength of the relationships between different constructs in the theoretical foundations of CBASP. Methods. A systematic literature search was conducted identifying research reporting the effects of CBASP intervention on interpersonal functioning in the clinical samples affected by PDD or depression of chronic nature but not meeting all the criteria for PDD. The search yielded nine papers which met inclusion and exclusion criteria. The Effective Public Health Practice Project quality assessment tool was employed to assess the quality of the included studies. In order to collect data for empirical study, a cross-sectional design was used. Clinicians working in the mental health teams in the local board were asked to identify adult patients on their caseloads who were affected by PDD. The clinicians were then invited to introduce the study to these patients and, if the patient showed an interest, offer them a questionnaire pack to read at home. Thirty-two patients with PDD completed and returned a set of questionnaires measuring childhood trauma, pre-operational functioning/reflective functioning, interpersonal difficulties, and depressive symptoms. A series of multiple regression analyses were used to analyse the results. Results. The systematic review provided evidence supporting the hypothesis that CBASP intervention leads to an improvement in the area of interpersonal functioning. The majority of the assessed studies demonstrated the improvements on the measures of interpersonal functioning, while all of the studies showed reductions in depressive symptoms. The methodological quality of the studies has been evaluated to be of good or very good standard which strengthened the reliability and validity of the results. Findings from the empirical study, somewhat surprisingly, failed to demonstrate the hypothesised association between childhood trauma, pre-operational thinking, interpersonal difficulties and the severity of depression. Childhood adversity, pre-operational thinking and interpersonal difficulties did not predict the severity of depressive symptoms. The relationship between childhood trauma and interpersonal functioning, as well as interpersonal functioning and depression, did not reach statistical significance, even when the subscale of the Inventory of Interpersonal Problems (Horowitz, Alden, Wiggins, & Pincus, 2000) measuring a hostile submissive interpersonal style associated with persistent depression, was entered into the model. Discussion. The findings from the first chapter of this thesis provide evidence suggesting that CBASP intervention leads to an improvement in the area of interpersonal functioning and reduction in depressive symptomatology. Importantly, the review's results demonstrated that while the assessed studies were primarily of good quality, more studies investigating specific mechanisms of change involved in the CBASP intervention are needed. The analyses which were part of the empirical study revealed the lack of associations between the constructs used by McCullough in his theory of persistent depression. While it is possible that the relationships between the discussed constructs are weaker than previously established, there have been a number of methodological limitations, such as a potentially unrepresentative sample and its small size, which might have contributed to the absence of predicted effects.

Background: The past decade has seen an increase in the use of communication technology such as smartphones and social media platforms. Although this improvement in technology might support enhancing communication, socialisation and even education, it also increases the risk of child sexual exploitation. Not only do more children now have access to technology to share personal information which could then be exploited, but more individuals have access to that technology to download, produce and share children sexual exploitation material (CSEM). It is impossible to have an accurate understanding of the prevalence of individuals having sexual interest in children (SIIC) and accessing CSEM who have not been caught. Research suggests that SIIC is commonly seen in the general population and does not solely prevail in sex offender populations. There has been an increase in the past decade in CSEM offences and convictions and organisations have been implemented to support individuals who self-report SIIC. Although research shows that these individuals who committed CSEM offences generally are at low risk of reoffending, certain factors do increase that risk. Law enforcement and criminal justice professionals are required to evaluate their level of risk to inform management, supervision and treatment in the community. The Child Pornography Offender Risk Tool (CPORT) was created specifically for this offender population and has been found to show significant predictive validity for any recidivism and any sexual recidivism; but has not been validated yet in a Scottish population. Method: Firstly, a systematic review of the literature was conducted to investigate the prevalence of individuals who self-report SIIC and their correlates to obtain a better understanding of the phenomenon. Secondly, the empirical research study aimed to replicate the most recent CPORT validation study to investigate the CPORT’s predictive validity in a sample of 144 Scottish CSEM offenders. Like the CPORT validation study, Receiver Operating Characteristic (ROC) and logistic regression analyses were conducted to explore its predictive validity. In addition, the CPORT’s Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were added to the investigation of its predictive validity in this study. Results: A total of 27 studies were analysed in the systematic review and results indicated a mean prevalence rate of SIIC between 16%-21%. Findings also suggested correlates of SIIC such as the presence of mental health problems and adverse childhood experiences. In the empirical research study, ROC and logistic regression analyses indicated that the CPORT significantly predicted any recidivism (Area Under the Curve, AUC = .79), any sexual recidivism (AUC = .79) and CSEM recidivism (AUC = .75), suggesting that it is a valid risk assessment tool for Scottish CSEM offenders. These results were also supported by the other indicators of predictive validity assessed in this study. Conclusions: Overall, the findings from the systematic review suggest that selfreported SIIC in the general population is relatively common and some studies have indicated that individuals from the general public have already accessed CSEM or would do so if they were certain to avoid detection. However, prevalence rates did vary greatly from one study to another, depending on the definition of SIIC and recruitment method used. Generally, the findings indicated inconsistencies in terms of methodology and definition/diagnostic criteria of SIIC and poor external validity. The sensitive nature of this topic likely increases the difficulties that researchers encounter in recruiting representative samples as well as relying on participants’ self-reported answers. The empirical study indicated that the CPORT is a valid risk assessment tool to be used in a Scottish population of CSEM offenders. The implications of this research suggest that the CPORT could be used with a combination of other tools assessing dynamic and protective factors to inform relevant authorities and support them in the supervision and management of individuals with CSEM offences. Strengths and limitations of the systematic review and the research were discussed with implications for clinical practice and recommendations for future research.

In this Doctorate of Psychotherapy and Counselling Dissertation, I offer a variety of different perspectives on queer shame and body shame in the context of trekking experiences. The overall project of this thesis is to offer some glimpses into the ongoing and ever-changing process that surrounds these topics. I draw methodological inspirations from Mason's (2011) conceptualization of Facet Methodology as well as Gale's (2018) conceptualization of Methodogenesis. I approach this with a poststructuralist perspective that follows flashes of insight through various assemblages, drawing on Deleuze and Guattari (1987). Being inspired by Haraway (2016), I attempt to foster a more-than-human view of the world. I employ a variety of methods for this inquiry, drawing largely on writing-as-inquiry (Wyatt, 2019; St. Pierre, 2008; Richardson, 2008) and autoethnography (Holman Jones & Harris, 2019; Gale, 2018; Wyatt, 2019). Emphasis is also drawn from dialogue and the unfinalizability of subjects (Bakhtin, 1984; Frank, 2004; Willis, 2009; 2013). I draw on themes from queer theorists including Halberstam (2011; 2015), Holman Jones and Harris (2019), and Butler (1997), among many others. The chapters of this thesis each contribute something to understanding queer shame and body shame experiences, and then offer something that we might use to work with that shame productively. I have concluded by emphasizing the entangled nature of our realities, and our interconnectedness. We strive to build lives work living, lives which allow us to live and die well together. The greatest source of strength in precarious times is the making of queer kin. Connecting with our queer families that are more-than-human and stretched across aeon time opens the door of possibility for us to make use of (at least) six different ways of working with queer shame and body shame: Decoding, Multiplicity and Becoming Queer, Daemonizing, Suffering/Resisting/Hoping with, (Re)Storying, and Being Together in Precarity.

The field of mental health and gaming has grown with the surge of the digital gaming industry in the last thirty years. While research on video games in regard to mental health, especially their effects on children, concerns about pathological use, and potential applications health interventions, is becoming a known field of study, there are many more avenues for approaching games that have yet to be explored. There are three nexuses in which research into games and their relationship with mental health are underrepresented: 1. Qualitative, experience-focused research; 2. Research focusing on adult populations; and 3. Research on traditional games. Where these three nexuses meet, there is an absolute dearth of research. Given substantial previous work into the impact of games on human culture and society, and promising results from other populations and types of games, this thesis considers whether this might be a worthwhile subject area for future mental health research to expand on. With this epistemic gap in mind, this thesis uses an ethnographic approach grounded in social realism to provide a foundational inquiry into whether traditional games can be considered therapeutic for adults. The hope for this research is that its results may be applicable and usable by further academic work from a wide breadth of different disciplines and onto-epistemic approaches. Using the game Magic: The Gathering as a case study, this work analyses the digital artefacts and experiential accounts offered by players, the design elements that are worked into the game, as well as the personal experiences and insights of the author as a Magic player, therapist and researcher. By marrying observations and experiences from the ludic field of Magic: The Gathering with theories from counselling and psychotherapy, the author outlines a process by which we might determine whether an activity is therapeutic. By applying this definition to narratives and outcomes offered by players online, this research concludes that traditional games can be therapeutic for adults, and further inquiry is needed to fully understand what impacts and potential benefits traditional games could have on the field of mental health for adults. With this conclusion in mind, this thesis also offers an understanding of how one might theorize or conceptualize the ways a game can be therapeutic. This thesis maps out a potential path through which therapeutic affect evident in outcomes may develop in relation to game-play interactions, through a process of working with culturally established boundaries and expression both in-game and in the community that constitutes a process of contained reality-testing. This process is also explored alongside the complex relationship and entanglement of wider social discourses and contexts that Magic is a part of, such as assumptions made about games as a whole as well as issues of difference and diversity in gaming. In doing so, this research offers a model of how mental health research into games can be applied at an experiential level, as well as creating a reference point for the potential further application of counselling and psychotherapeutic theories in game.

There is a limited amount of academic research within social sciences investigating the experiences of queer people in post-Soviet Central Asian countries. My study aims to address this gap in the literature by focusing on the everyday narratives of queer people in Kazakhstan within a framework of power and agency, primarily using the theories of Michel Foucault and other scholars such as Hannah Arendt and Erving Goffman. In this study, ‘queer’ is understood as broadly encompassing the whole spectrum of nonheterosexual and non-cisgender identities. By looking at the narratives of queer people within their socio-historical context, this study aims to elucidate two key issues: in Kazakhstan, what regulates queer lives, and how do people negotiate their queer subjectivities? The qualitative study uses a Foucauldian-informed thematic analysis of interviews with eleven people who identify as queer and live in Kazakhstan. The findings reveal that practices of regulation of queer people in Kazakhstan range from legal and medical regulation, surveillance within different everyday contexts, limiting career prospects, and internalised gaze and oppression. Crucially, I argue that despite the manifold regulatory practices, the narratives of queer Kazakhstani participants of this study highlight the artful ability to navigate and negotiate the existing regulatory and power structures to live fulfilling and authentic lives. This study contributes to the scholarship on post-Soviet gender and sexualities by developing a deeper understanding of nonheterosexual and non-cisgender subjectivities in the context of Kazakhstan.

Recent theories in the field of computational psychiatry regard schizophrenia (SCZ) and autistic spectrum disorders (ASD) as impairments in Bayesian inference performed by the brain. In Bayesian terms, perception is a result of optimal real-time integration of sensory information (’likelihood’), which is intrinsically noisy and ambiguous, and prior expectations about the states of the world (‘prior’), which serve to disambiguate the meaning of the sensory information. Priors capture statistical regularities in the environment and are constantly updated to keep up with any changes in these regularities. The extent to which prior or likelihood dominate perception depends on the uncertainty with which they are represented, with less uncertainty resulting in more influence. Individuals with ASD and SCZ might show impairments in how they update their priors and/or how much uncertainty there is ascribed to prior and likelihood representations, leading to differences in inference. While this Bayesian account can be argued to be consistent with many previous experimental findings and symptoms of SCZ and ASD, recent experimental work inspired by these ideas has produced mixed results. In this work, we investigated possible Bayesian impairments in SCZ and ASD experimentally by addressing some of the methodological limitations of the previous work. Most notably, we used an experimental design that allows to disentangle and quantify separate influences of priors and likelihoods, and we tested both SCZ and ASD patient groups as well as autistic and schizotypy traits in the general population. We administered a visual motion perception task that rapidly induces prior expectations about the stimulus motion direction, leading to biases and occasional hallucinations that can be well described by a Bayesian model. In this task, autistic traits were found to be associated with reduced biases, which was underlied by more precise sensory representations, while the acquired priors were not affected by autistic traits. Patients with ASD, however, showed no evidence of increased sensory precision, while there also were no impairments in the acquisition of priors. We also found no effects in the acquisition of priors or sensory representations along schizotypy traits and in patients with SCZ. However, under conditions of high ambiguity SCZ patients were less likely to hallucinate the stimulus than controls. The second part of the thesis is focused on further exploratory analyses conducted using these same datasets. First, we investigated post-perceptual repulsion effects in our task and whether they were related to trait or group differences. We found clear evidence of repulsion from the cardinal directions. In addition to that, we found evidence for a repulsion from the central reference angle, which was randomly selected for each participant and which could only be inferred from the stimulus statistics. Furthermore, we found the repulsion from the central reference angle to be reduced along schizotypy traits. Interestingly, in both SCZ and ASD groups this repulsion was also found to be negligible. While these results are exploratory, they might point to a trans-diagnostic features of ASD and SCZ. Second, we investigated within-trial dynamics of evidence accumulation by constructing a Continuous Choice Drift Diffusion Model (CDM) – an extension of the classical binary choice drift diffusion model. The results of this model showed that increased sensory precision along AQ found in a Bayesian model was underlied by faster drift rates, while slower responses and reduced hallucinations in SCZ were explained by a larger decision threshold. In addition, this model provided a more complete characterization of the performance in this task (by including reaction times) and it serves to emphasize the importance of accounting for exposure to stimulus duration and judgement time in future studies investigating Bayesian inference. Together, this work provides novel experimental evidence that speaks to the hypothesis of impaired Bayesian inference in ASD and SCZ. Furthermore, the analysis of reference repulsion effects and within-trial dynamics provide additional insight related to SCZ and ASD differences that extend beyond the Bayesian framework.

The t(1;11) translocation is a mutation unique to a Scottish pedigree, members of which have been diagnosed with schizophrenia, bipolar disorder, recurrent major depressive disorder and other related disorders. The translocation is significantly linked to increased risk of these diagnoses. It disrupts three genes, only one of which, DISC1, encodes a protein. A number of experiments have explored the function of DISC1 as a molecular scaffold and developmental regulator. DISC1 and its interactors have roles in processes of relevance to psychiatric disease. These include neuronal precursor proliferation, migration and integration in the developing and adult brain, neurite outgrowth, mitochondrial activity, which is particularly important in neurons due to their high energy demands, and intracellular trafficking, especially critical in neurons due to their highly elongated morphology. Although various DISC1 mutations have been investigated in the past, it is only with advances in technology that neural cells derived directly from translocation carriers, and therefore carrying the translocation plus their genetic background, have been generated and analysed. In addition a recently described mouse model mimics the effects of the translocation upon DISC1 expression. It does so by removing endogenous Disc1 exons corresponding to those distal to the breakpoint in translocation carriers, and fusing the remaining endogenous 5’ Disc1 genomic sequence to human chromosome 11 genomic sequence distal to the translocation breakpoint. The result is a chimeric gene with 5’ mouse Disc1 joined to a segment of human DISC1FP1, the non-coding fusion partner of DISC1 located on chromosome 11. This leads to loss of wild-type Disc1 and prediction of chimeric transcripts encoding aberrant C-terminally truncated forms of Disc1. This thesis builds on the work of previous researchers to characterise the RNAsequenced transcriptome of ‘cortical’ neurons derived from induced pluripotent stem cells from various members of the pedigree. Both heterozygous and homozygous mutant mice have also been utilised to generate RNA-sequencing data from the hippocampus and cortex. The thesis not only describes the differential expression of genes and exons, but also carries out a series of analyses to examine whether proportions of certain cell types are altered, as well as whether differentially expressed genes are highly associated with specific cell types. RNA-Seq data have been analysed for differential expression at the gene and individual exon level using DESeq2 and DEXSeq, respectively. This has revealed over 1,200 differentially expressed genes in human neurons carrying the translocation, which predict changes to functions relating to intracellular transport and synaptic activity. In addition, a number of genes have been verified by RT-qPCR as being differentially expressed in these neurons. These include genes of known relevance to schizophrenia such as DRD2, which encodes the D2 dopamine receptor, NTRK2, which encodes the BDNF receptor NTRK2, and BBS1 which encodes the DISC1 interactor and centrosomal protein BBS1. The human neurons also show significant overlap with previously published dysregulated genes in human neurons carrying other DISC1 mutations, as well as with genes associated with schizophrenia by large-scale genome wide association and copy number variation studies. Human neuron RNA-Seq data have also been examined for evidence of local effects of the translocation upon gene expression, and no obvious strong effect was found. The pattern of gene dysregulation in heterozygous mutant mouse cortex overlaps with that of the mutant human neurons. Gene expression changes in the mutant mouse cortex have also been verified by RT-qPCR in the genes Arc and Avp, and the list of implicated genes also shows overlap with genes associated with schizophrenia by large-scale genome wide association and copy number variation studies. An RNA-Seq deconvolution analysis was carried out to look for evidence of altered proportions of cell types at both the broad and more specific cell type level. This compared the observed expression of hundreds of genes in in the RNA-Seq samples against their expression in publically available RNA-Seq data of specific cell types. There does not appear to be any strong and consistent effect of the t(1;11) or mouse mutation on cell proportions. However, the data indicate greater than expected dysregulation of genes that are highly enriched in specific cell types. This includes certain subtypes of astrocyte. Mutant mouse cortex also shows dysregulation of genes associated with several subtypes of interneuron and pyramidal neuron, including parvalbumin positive interneurons. This indicates that, while the proportions of cell types appears to be unaffected by the translocation or mouse mutation, specialised cellular functions may be perturbed. To conclude, this thesis highlights a number of processes which appear to be disturbed by the translocation and mouse mutation. In all models, RNA-Seq evidence suggests signalling pathways of known relevance to psychiatric disease have been affected without significant alteration of cell proportions. This concurs with histological analyses of the mouse model by previous researchers. This thesis also describes the overlap between genes implicated in the study of this unique mutation as well as those implicated by studies seeking common or rare mutations predisposing to schizophrenia, supporting the hypothesis that different genomic risk variants and mutations converge upon certain molecular pathways that are especially important in this illness. The implication that the t(1;11) may alter the activities of certain cell types is also notable and future work can elucidate the cell-specific effects of the translocation.

This is a research project aims to reconceptualise reflexivity and experience to think anew about making sense of ourselves. Methodologically, I think through different traditions to diffract my concepts of interest, arriving at – necessarily temporary – renewed articulations. The traditions that I mostly use are poststructuralism, posthumanism and to a lesser extent, psychoanalysis in a relational strand. The new conceptualisations that I put forward are not only theoretically – abstractly – important, as if theory could be divorced from life. Instead, these new conceptualisations are important because they produce new worlds: different ways of becoming a subject, different ways of articulating affective experience, different questions, different tools, different problems, and so on. In coherence with that, at different points throughout this research, I bring to the page how these reconceptualisations are influenced by my experiences – including my experience as a psychotherapist – and how these reconceptualisations produce me and my experience differently. Based on a relational perspective, we do not pre-exist our relating but are produced through relating – not only in interpersonal terms but in materialdiscursive ones. In coherence with this, my conceptualisation of reflexivity shifts the understanding of it as a discrete activity performed by a bounded subjectivity that captures how things ‘are’ to understand it as an ever-present way of relating to ourselves that is not performed by an already bounded subject but produces a particular kind of subjectivity and a certain world. With this relational, material-discursive and performative understanding of reflexivity, I contend that the possibility of questioning our assumptions is not given by an individual decision but requires yielding to the foreignness of unknown fields that might unwittingly shift our assumptions and hence we are able to see what we were previously taking for granted. Furthermore, I emphasise the need to develop a meta-reflexivity that asks about the ways of relating that we are enacting and what they are producing. Originally, my conceptualisation of reflexivity is made with, not against, diffraction. I contend that we never find pure reflection or pure diffraction but different shades of them, as in a diffraction pattern. Moreover, I propose that when we hold diffraction as the superior term, we unavoidably betray our best intentions and reproduce the representationalism that we were so keen to avoid. I further elaborate the benefits of a diffracted reflexivity and of using meta-reflexivity with diffraction. Throughout the thesis, I argue to regard different concepts and theories as more or less useful for particular contexts because of how they produce these very contexts. I value the theories in their productions rather than in their truthvalue because there is not a world to discover but a production of worlds through practices of knowing. In coherence with this, I read the concept of experience through the lenses of existential phenomenology, poststructuralism and posthumanism. I let myself be taken by each of these traditions, opening up to what they produce. I, intra-actively with the three traditions – and my psychoanalytic background – arrive at an articulation of the concept of experience. I think of experience as an impersonal affect with its own force to produce us as subjectivities. This experience can be elaborated from the felt sense rather than from our cognition to enable a movement in our experience and in our ways of subjectivation. Finally, I assert that we do need to critically consider where this experience/affect is taking us because it can lead to reproduce dynamics that can be detrimental. To conclude, in this thesis I grapple with reflexivity and experience to think differently about the practices of making sense of ourselves. In very broad terms, I would say that I have arrived at the following ideas: 1. In making sense of ourselves we are also producing ourselves. 2. We do not make sense intentionally and separately from our relational, affective, and materialdiscursive engagements. Strictly, it is not that ‘we’ make sense of ‘ourselves’, but a greater intra-active assemblage makes sense and produces ourselves and the world in that movement. 3. There is no way of neutrally judging which ways of making sense and producing ourselves and the world are better or truer. 4. There is not a way to control the way in which we make sense, rather we ‘find ourselves’ making sense. And 5. Given the previous points, the only thing we can do is to be curious about how we are relating to ourselves when making sense and to wonder what that relating is producing.

This thesis critiques the concept of narrative coherence through an in-depth inquiry into the lived experience of narrative incoherence in counselling and psychotherapy. It questions whether lived experience necessarily requires narrative structure and the extent to which a coherent narrative is essential for psychological and emotional well-being. It thus attempts to depathologise the experience of narrative incoherence, instead honouring those moments in therapy when words quite literally fail us. Adopting writing as inquiry as its methodological foundation, the thesis continuously moves between experiential self-searching and intellectual engagement with theoretical insights. I draw particularly on conceptual resources offered by Butler, Foucault, Wittgenstein, Winnicott, Freud, Leader and the theory of the dialogical self. I write into my personal experiences as a client in therapy and as a therapist and this analytical work is complemented by reflections on my experience of a short-term sandplay process, undertaken specifically for this research project, which aimed to surface the interstices of language and the non-verbal therapeutic process. Parallel to its questioning of the demand for narrative coherence is this thesis's challenge to the linear, well-structured and well-articulated scholarly voice of traditional doctoral thesis work. Methodologically and stylistically, this thesis stays close to that which is inarticulate and unstructured, which is often termed incoherence. Instead of presenting a planned linear process, I argue that the research process of this thesis is an unforeseeable and unpredictable journey into the unknown in which I encounter rather than choose the conceptual resources I use. This thesis concludes with three main points, namely 'letting go', 'holding on' and 'to play'. I encourage therapists to let go of the obsession with and demand for coherent narrative as these can silence, alienate and pathologise individuals. Meanwhile, the research process also highlights the necessity of telling one's story to a caring other, and the predicament between the impossibility of expression and the necessity to tell and to be known. In relation to this, I encourage therapists to stay with and listen to what is unsayable and unnarratable without demand. Lastly, this thesis puts forth the value of playfulness when working with the concept of narrative coherence and incoherence, calling for a blurring boundary between the two.

Background/Aims: People with a diagnosis of psychosis often experience stigmatising social encounters. These social encounters may influence the beliefs people hold, as research suggests that people develop a range of processes in an attempt to interpret information about both themselves and others. The internalisation of negative stereotypes about psychosis is one process used to explain how people's beliefs are influenced. Cognitive models highlight the relationship between self and social knowledge and mood. How people process social information might therefore have an important role in pathways to distress in psychosis. There is limited understanding of how different expressions of emotional distress might relate to the processing of social information. This research portfolio therefore has two aims. Firstly it aims to systematically review literature on the relationship between internalised stigma and distress for people with a schizophrenia spectrum diagnosis. It also aims to explore the relationship between attachment style, reflective functioning, personal beliefs about illness, and emotional distress in people who experience psychosis. Method: These two aims are addressed through two studies. The first study is reported in Chapter 1, where literature exploring the relationship between internalised stigma and measures of emotional distress was systematically reviewed. For this review, a search of electronic databases was conducted, included studies were assessed for quality, and results were outlined through a narrative synthesis. The empirical project reported in Chapter 2 employed a cross-sectional design to gather quantitative data from people who had a diagnosis related to psychosis. Mediation modelling was then used to explore cognitive appraisals as mediatory variables between attachment anxiety and emotional distress whilst controlling for psychotic symptomatology as a potential confounding variable. Results: Thirty studies were included in the systematic review, with over half of these being cross-sectional in design. Systematic review findings indicate a significant association between internalised stigma and depression, however the association with other measures of distress was inconsistent. Limited data was therefore available regarding the utility of cognitive interventions focusing upon internalised stigma for improving symptoms of distress in psychosis. Results from the empirical study indicate associations between attachment anxiety, cognitive appraisals, and emotional distress but not reflective functioning. Personal beliefs about illness regarding shame and control were found to mediate the relationship between attachment anxiety and distress. Conclusions: When reviewed systematically the relationship between internalised stigma and distress remained unclear. This is due in part to methodological limitations of included studies which did not allow the exploration of whether these negative beliefs about the self in relation to others around them leads to distress. However, findings from the empirical study suggested personal beliefs about illness could influence the relationship between attachment and emotional distress. Future interventions focusing upon internalised stigma as a vehicle for improving symptoms of distress in psychosis might therefore target perceptions of shame and control whilst recognising a wider range of outcomes for distress.

Relational therapies often require the therapist's wholehearted and conscious use of self as essential to the therapeutic process. I argue that the self I bring to a client is disintegrated and often shattered and that the expectation of integration in the therapist's self is impossible to meet. This study is aimed mainly towards practitioners as readers, in an attempt to uncover the vulnerability of therapists in light of the complex power relationships we enter into and to deconstruct the myth of the undifferentiated, fixed self of the therapist. I do this by using writing as a method of inquiry, within a post-structural research paradigm, to create a detailed exploration of inter-cultural and inter-gender therapy with a fictional client, written from my perspective as a therapist who assumes a minority identity. The writing is left deliberately disjointed and disconnected to embody this deconstructive stance. From a post-colonial and feminist angle, I explore various themes around presence, voice, gender, race, shame, disconnect, dissociation, spirituality, consciousness, sex, integration and oneness within the context of using my self to work therapeutically with the fictional client. The jumbling and jolting experience of moving through the various realms of self is my whole world. I am left fragmented, lost and incoherent as I write into these experiences, which leaves me true not only to the method, wherein "getting lost" becomes key to creating knowledge, but also to the confusing and painful process of psychotherapy itself.

How is the voice healing? Over the past few decades, research has begun to uncover the therapeutic benefits of vocal practices. Research results have evidenced that different forms of vocal expression positively influence the quality of life of an adult emotionally, mentally, physically, psychologically, and spiritually. However, different theoretical approaches, different methods, and different samples have left a heterogeneous picture of the reported benefits. It remains unclear how individuals experience healing through vocal practices, nor do we know much about the qualities that characterise each practice. This research aims to explore how individuals experience healing and transformation through different vocal practices, including therapeutic voicework, creative singing, and performance singing. In this study, these vocal practices are grouped under the term 'vocal creativity'. The research problem was formulated with the following question: What is the nature and meaning of experiences of vocal creativity, and what can these experiences tell us about the human voice's potential for healing? To reveal the elements of each vocal practice, and the mechanisms behind individuals' experiences of healing through the voice, this study adopts a heuristic methodology to yield in-depth findings. More specifically, a heuristic comparison study was undertaken to draw out features that characterise each practice and the therapeutic benefits different forms of vocal creativity have in common. As an additional way to gain knowledge and present key findings, I created songs and lyrical poems to access an embodied understanding of individuals' experiences. To generate data, I engaged my experience of vocal creativity and conducted conversational interviews. Some of my autobiographical contributions were analysed integrating Process-Experiential Theory to produce a richer understanding of how I have healed and transformed through vocal creativity. The ten respondents of the conversational interviews were men and women, aged between 25-67 years old, from the United States, England, and Spain. The present study provides important insights into the significance of the voice for healing that may be useful for practitioners both within, and outwith, the arts therapies. Integration of vocal creativity and Process-Experiential Theory elaborates on Emotion-Focused Therapy and expands the theoretical base for vocal practices, suggesting that using the voice as an embodied and symbolic tool for emotion may assist in the facilitation of emotional processing, and in working with internal multiplicity. The study's findings illuminate underlying qualities, processes, and mechanisms in experiences of vocal practices, and elucidate contexts and conditions that enabled or inhibited ways of healing through the voice, all of which are seldom addressed in current scholarship.

It is now accepted that Schizophrenia, a neurodevelopmental disorder which affects around 1% of the population, is influenced by both genetic and environmental risk factors. Schizophrenia is evidenced as being heritable with twin-heritability estimates of around 80%. Recently, the disorder has been demonstrated to be polygenic in nature; many genetic variants with individually small effects contribute to the overall phenotypic variation. Furthermore, cannabis use, adverse events, urbanicity, obstetric complications and migration, are five environmental risk factors that have been evidenced as being associated with an increased risk of developing the disorder. Abnormalities in brain structure are also well evidenced in individuals with schizophrenia, in particular, reduced cortical thickness, volume and surface area have been linked to those with schizophrenia when compared to healthy controls. It has been posited that these cortical alterations may predate disorder onset, for example, disruptions in brain development may be a function of experiencing schizophrenia-associated genetic and environmental risk factors. However, the link between genes, environment and brain structure within schizophrenia remains unclear. In this thesis, we aimed to examine whether genetic and environmental risk factors for schizophrenia directly impact cortical brain structure. Methods and Results The current aims were assessed using measures of cortical thickness, volume and surface area, as defined by FreeSurfer, in three separate studies. Firstly, ANCOVA models were applied to a case-control sample, the Scottish Family Mental Health (SFMH) study, ncontrols/npatients = 41/58) to determine whether PolyGenic Risk Scores for Schizophrenia (PGRS-SCZ) are associated with lower cortical thickness both globally and within regions of interest (frontal and temporal lobes) as well as to examine whether the effects of experiencing an accumulation of the five environmental risk factors (outlined above) is associated with greater cortical thinning (Chapter Two). The results indicated that an increased PGRS-SCZ was related to lower, global cortical thickness in the whole sample and not a result of group differences. With regards to environmental effects, the more environmental risk factors experienced, the lower the cortical thickness, this was specific to the temporal lobe. Secondly, to further investigate the link between environmental risk factors of schizophrenia, we focused on birth weight as a proxy for obstetric complications (Chapter Three). Linear mixed effects regression (LME) models were used to assess whether birth weight was associated with cortical thickness, surface area and volume in a UK Biobank (UKB) sample (n = 1,680). We then applied Mendelian Randomisation (MR) to determine if birth weight-associated genetic variants were causally related to cortical structure. The results in this chapter suggested that higher weight at birth was associated with larger cortical volumes and surface area, both globally and in several cortical sub-regions. In contrast, a negative association was found between birth weight and cortical thickness in the lateral occipital parcel. MR analysis suggested a causal link of birth weight, as indexed by genetic variants, and insular lobe cortical volume as well as surface area globally, in the insular lobe and in middle temporal, medial orbitofrontal and inferior frontal gyrus parcels. Lastly, we tested whether the same association between PGRS-SCZ and cortical thickness (outlined in Chapter Two) could be replicated within a subset of UKB (Chapter Four). For this, we again utilised LME models using the second genetic data release of UKB (n = 2,864). We tested this globally, lobarly and within 27 bilateral cortical parcels for each of these parameters. We found a higher PGRS-SCZ to be associated with lower global cortical volume and thickness as well as insular lobe cortical thickness. To further test potential environmental influences (as outlined in Chapter Three) on these effects, we used a liner regression model to test for a relationship between PGRS-SCZ and birth weight as well as LME models to test for interactional effects. No relationship was found between PGRS-SCZ and birth weight nor were there any significant interactions found between PGRS-SCZ and birth weight on cortical structure Conclusion Together, these studies highlight the fact that both genetic and environmental risk factors for schizophrenia may, indeed, directly but differentially impact cortical brain structure. This information may help us to further understand the progression of the disorder but also, by identifying and addressing these risk factors early, we may be able to minimise the impact that the disorder can have on cortical brain structure; particularly in relation to potentially modifiable factors, such as birth weight. We also highlight the importance of using large samples and replications in order to examine such relationships.

This thesis follows the emergence of a biosocial community and shows the importance of social relations for British and American people living with body-focused repetitive behaviours (BFRBs). It is based on sixteen months of ethnographic fieldwork in multiple sites across the UK and the US. I describe the experiences of women, men, and young people living with hair pulling (trichotillomania) and skin picking (dermatillomania), as well as their loved ones, health professionals, researchers and hairdressers working in the field of BFRBs. I present an in-depth view of what it is like to live with BFRBs, and the stigma and risk involved in the process of concealing and revealing to others. Exploring the complexities of how BFRBs are embodied, I show the shame and confusion that people feel towards their own bodies, triggering negative perceptions of the self. The suffering caused by BFRBs is reflected in families, with parents sharing feelings of loss, grief and frustration with their BFRB children. I expand on kinship theories to unpack these experiences through the concept of intersubjectivity, illustrating how parents are both connected and separated by their shared experiences with children. From these domestic challenges stem care practices that blur the boundaries between love and harm. Within the wider contexts of care, health professionals are described as unsupportive and uninformed, and people rarely receive effective support from the medical sphere. But despite the disappointments in medical care, diagnosis still has a value, and the journey that people living with BFRBs go through towards biosociality is dependent on the medical label. People therefore transition from isolated shame to connecting with others who share their embodied experience, forming relationships that are comparable to kinship ties. I argue that the process of finding and forming the biosocial BFRB community, allows people to overcome long-term feelings of shame, and leads to alternative notions of recovery. But biosociality is complex; it involves conflict, issues of inclusion, and ongoing work in order to be sustained. Due to the limits of biosociality, some people in the BFRB community are inspired towards biosolidarity; where BFRB experiences are turned into acts of advocacy that raise awareness and make these disorders visible in new ways. This thesis involves combined ethnographic and auto-ethnographic perspectives, and hopes to bring BFRB experiences to the attention of scholars, professionals and lay people living and working with mental disorders.

In the context of developmental psychopathology and the psychological and social risk factors associated with psychosis and 'schizophrenia', this thesis proposes that early attachment interactions underlie the development of reflective function and emotion regulation which contribute to the emergence of negative symptoms. Attachment, reflective function and emotion regulation have been associated with mental health difficulties characterised by emotion dysfunction and interpersonal problems. However, there is very little research examining these factors in relation to the development of negative symptoms, perhaps due to historical conceptualisation of negative symptoms as 'non-affective' phenomena. Therefore, less research has been performed into possible interpersonal affective mechanisms driving negative symptoms than other disorders. Two studies, each using a quantitative cross-sectional design were used to examine the following primary questions: 1) Does attachment insecurity predict negative symptoms? 2) Is this relationship mediated by reflective function and emotion regulation? 3) Is psychological distress associated with negative symptoms? Secondary questions were: 1) Do attachment, reflective function and emotion regulation predict psychotic experiences? 2) Does self-agency mediate the relationship between attachment and negative symptoms? The first empirical study was a large-scale survey of 1647 participants aged between 16 and 35 years recruited online from the general population. Participants completed questionnaires measuring attachment, reflective function, emotion regulation, negative symptoms and distress. Data was analysed using univariate statistics, multivariate statistics and structural equation modelling. Results demonstrated that attachment insecurity predicted negative symptoms and this relationship was partially mediated by emotion regulation. Reflective function also predicted negative symptoms and distress significantly covaried with negative symptoms. Self-agency also acted as a partial mediator between attachment, reflective function and negative symptoms. Attachment, reflective function and emotion regulation also predicted psychotic experiences. Method The second empirical study examined attachment, reflective function, emotion regulation and negative symptoms in a help-seeking population of 52 young adults attending mental health and third sector services in Edinburgh and the Lothians. Participants were administered the Clinical Assessment Interview of Negative Symptoms (CAINS), Comprehensive Assessment of At-Risk Mental States (for psychosis) (CAARMS), and the Adult Attachment Interview (AAI) scored for attachment and reflective function. Participants also completed questionnaires measuring distress, emotion regulation, interpersonal problems and self-agency. Data was analysed using appropriate univariate statistics, multivariate statistics and path analysis. The sample was divided into three groups according to psychosis: non-at-risk mental state (n=17), at-risk mental state (n=18) and first-episode psychosis (n=17). Results The sample was characterised by high levels of distress, interpersonal problems, attachment insecurity, dysfunctional emotion regulation and low reflective function. Attachment insecurity significantly predicted reduced reflective function which mediated the relationship between attachment insecurity and negative symptoms. Emotion regulation was not predicted by attachment or reflective function, nor did it predict negative symptoms. Distress significantly covaried with negative symptoms. Discussion These results highlight the importance of investigating the underlying psychological mechanisms and considering the role of affect in the development of negative symptoms. Attachment insecurity, emotion regulation and reflective functioning play a role the emergence of negative symptoms which are related to psychological distress. Therefore, to improve understanding and treatment of negative symptoms, it is important to focus on these interpersonal affective mechanisms and consider how they interact with distress to contribute to negative symptoms.

Abnormalities of reward processing, decision-making and emotion processing are core features of bipolar I disorder (BD). These processes are closely linked with fronto-striatal and midbrain circuitry. I sought to test whether dysfunctions of these pathways were present in BD and whether they related to genetic vulnerability to illness or resilience. I recruited twenty-five BD I patients each with their unaffected sibling, and compared them to 24 healthy age- and gender-matched controls. In chapter 1, I provide a research background and literature review. Chapter 2 describes the neuropsychological assessments which demonstrated trait-related deficits in working memory with slower processing speed representing an endophenotype. Chapter 3 describes the implicit/ explicit facial emotion processing task performed during event-related functional MRI (erfMRI). Pairwise comparisons demonstrated implicit processing was associated with increases in lingual gyrus and insula activations and explicit processing elicited reduced fusiform activations in patients compared with controls. Increased posterior cingulate activations and reductions in putamen and cerebellar activity were found in siblings compared to controls, and reductions in parietal activations were noted in siblings compared to their ill relatives. These findings suggest over-activations in regions involved in facial expression recognition and attentional shifting (lingual and insula respectively) and deactivations in a region important for the perception and recognition of faces (fusiform) represent correlates of disease expression. Additionally regional deactivations associated with category learning and attentional processing (parietal, putamen and cerebellar) and increased activations in a region involved in emotional salience (posterior cingulate) may represent adaptive responses associated with resilience. Chapter 4 describes an instrumental reward-learning task performed during erfMRI. Data were analysed at whole brain level and using a priori region of interest analyses in ventral striatum/midbrain and prefrontal cortex (PFC). Results included increased ventral striatum activation in association with the difference between observed and expected rewarding outcomes (the prediction error (PE)) in patients compared to controls. Decreased prefrontal activations were seen in the patient and sibling groups compared to controls in association with the learning of the value of the conditioned stimulus. These findings suggest that i) PE associated circuitry (striatal) overactivation, and ii) prefrontal deactivations underlie the genetic vulnerability to BD.

Introduction and Aims: Recovery from severe and enduring mental health difficulties, such as psychosis, continues to be researched and is an area of importance regarding the development of successful interventions to help increase quality of life and wellbeing. Systematic Review - This aimed to review the current literature base regarding studies which have investigated change in self-compassion as an outcome measure, pre to post intervention, for individuals living with severe and enduring mental health difficulties. Empirical Study - Using a qualitative approach, this study was interested in investigating young people's experiences of early psychosis. In particular, to investigate 1) the importance of autobiographical memories in young people's recovery and 2) in what way early adverse experiences and memory formation affect future thinking and establishing an overall sense of self during this recovery process. Methodology: Systematic Review - Search terms were used within PsychInfo, Embase and Ovid databases in order to locate all papers which included a severe and enduring population and used compassion as an outcome pre and post an intervention. Fourteen studies were included for review. Quality was rated, using adaptations of the NICE and CASP checklists; two small meta analyses were also conducted in order to pool effect sizes. Empirical Study - Eight young people, from 16-19 years, were interviewed using a grounded theory approach. Interviews were transcribed and coded following each individual interview and developed over time; line by line coding was initially used, followed by the development of more focused codes and salient themes. This was combined with the completion of quantitative outcome measures in order to triangulate the data. Results: Systematic Review - Studies were grouped into two separate categories: those which had a control group and those which had a repeated measures design. Pooled effect sizes illustrated that self-compassion was shown to increase significantly in the intervention group in comparison to controls, and for groups over two time points. Studies are discussed separately, focusing on limitations, and then drawing on similar themes. Empirical Study - Salient categories which emerged from the interviews were: interpersonal connections, self-identity, choice and freedom, recovery and autobiographical memory. These are discussed in addition to sub-categories and with reference to quotes from young people. Locus of control was used to understand the findings, linking them to theory and models based in the literature. Conclusions: Systematic Review - The current review offers some support to the literature and suggests that self-compassion can be generated and increased in this population, who are susceptible to self-stigma and shame. The varied quality of studies, however, suggests a need for higher quality RCTs in order to increase our understanding and aid the development of more successful interventions for this complex population. Empirical Study - Findings illustrate the importance of helping young people develop coherent narratives of their experiences, in turn helping to build a sense of sense following early psychosis. Locus of control was found to be a helpful concept in viewing recovery and is helpful to consider when working with this population. Results from the current study were also shown to support literature in the area of positive contributions and empowerment, which are shown to be key for young people during recovery and will be helpful areas for further research.

Purpose The systematic review aimed to identify, synthesise and evaluate the state of evidence regarding quality of social relationships and interpersonal patterns experienced by people with early psychosis, including those with at risk mental states (ARMS). The research study aimed to explore relationships between experiences of trauma and neglect, ability to mentalise and interpersonal problems in people with psychosis. Method The review article included a systematic search of four electronic databases, the search revealed eighteen articles. The research study involved gathering data via questionnaires, a semi-structured interview and a cartoon-based task from 48 participants with experience of psychosis. These outcome measures assessed childhood adversity, trauma related distress, ability to mentalise, interpersonal problems and psychotic symptomatology. Results The review revealed that people in the early stages of psychosis and those with ARMS experience poor quality relationships and have difficulties with relating to others, such as struggling to prioritise and assert their own needs. These difficulties appear early in the disorder and there was some evidence to suggest they may be related to distress. Further research is required to establish the predictors and consequences of these difficulties. The research article found that participants experienced high levels of trauma related distress and poor mentalising ability. Experience of childhood trauma and neglect was found to influence interpersonal problems via emotional distress and trauma related distress. Trauma related distress was also found to mediate the relationship between childhood adversity and negative symptoms. Mentalising was found to be unrelated to trauma and interpersonal problems. Conclusions Taken together the above findings indicate that people with psychosis experience relational difficulties. These difficulties appear to occur early in the disorder and potentially prior to onset. Difficulties in relationships appear to be influenced by experience of trauma, trauma related distress and emotional distress, indicating that a person's adaptation to trauma is significant. Distress (e.g. depression, emotional distress, trauma symptoms) appears to be related to relational functioning. Results reflect that some people may cope with the aftermath of trauma by 'deactivating' and numbing emotional experiences, as trauma was found to indirectly affect negative symptoms via trauma related distress. Findings regarding mentalising appear inconsistent and potentially measures of mentalising require review and refinement.

This thesis is an exploration of two interconnected areas: Acceptance and Commitment Therapy (ACT) training for helping professionals (HPs) and psychological flexibility in helping professionals. The ACT model holds that HPs need to be psychologically flexible (or, herein, flexible) in order to be effective ACT practitioners, and thus a primary goal of ACT training is to enhance participant flexibility. The first chapter is a systematic review of studies that have evaluated the effectiveness of ACT training. It focused on ACT training practices and outcomes related to knowledge, skills, and psychological flexibility in HPs. The results of this review suggested that ACT training can be effective in providing HPs from a range of occupational background with the necessary knowledge and competency to deliver ACT interventions. Furthermore, ACT training can increase HP flexibility. However, confidence in these findings is limited due to methodological weaknesses, particularly variability in ACT training practices, inconsistent use of available measures, a lack of psychometrically robust measures to assess ACT knowledge, and the absence of a flexibility measure designed for use with HP populations. Recommendations were made regarding future research needs in this area, including the development of a HP-specific measure of flexibility. The second chapter reports on the development and initial validation of a measure designed to assess flexibility in the specific context of professional helping, called the Mindful Healthcare Scale (MHS). The results of two studies employing two separates samples of HPs provided good preliminary evidence of the MHS's factor structure and internal validity. The MHS was also found to converge in theoretically-consistent ways with other measures of flexibility and constructs related to the occupational functioning of HPs including burnout syndrome, self-compassion, and empathy. These findings suggest that the MHS may have considerable utility in relation to ACT training for HPs and may also advance our understanding of flexibility's role in HP occupational well-being and functioning.

Psychotic disorders such as schizophrenia and bipolar disorder have a strong genetic component. The aetiology of psychoses is known to be complex, including additive effects from multiple susceptibility genes, interactions between genes, environmental risk factors, and gene by environment interactions. With the development of new technologies such as genome-wide association studies and imputation of ungenotyped variants, the amount of genomic data has increased dramatically leading to the necessary use of Machine Learning techniques. Random Forest has been widely used to study the underlying genetic factors of psychiatric disorders such as epistasis and gene-gene interactions. Several authors have investigated the ability of this algorithm in finding single and interaction effects, but have reported contradictory results. Therefore, in order to examine Random Forest ability of detecting single and interaction effects based on different variable importance measures, I conducted a simulation study assessing whether the algorithm was able to detect single and interaction models under different correlation conditions. The results suggest that the optimal Variable Importance Measures to use in real situations under correlation is the unconditional unscaled permutation variable importance measure. Several studies have shown bias in one of the most popular variable importance measures, the Gini importance. Hence, in a second simulation study I study whether the Gini variable importance is influenced by the variability of predictors, the precision of measuring them, and the variability of the error. Evidence of other biases in this variable importance was found. The results from the first simulation study were used to study whether genes related to 29 molecular biomarkers, which have been associated with schizophrenia, influence risk for schizophrenia in a case-control study of 26476 cases and 31804 controls from 39 different European ancestry cohorts. Single effects from ACAT2 and TNC genes were detected to contribute risk for schizophrenia. ACAT2 is a gene in the chromosome 6 which is related to energy metabolism. Transcriptional differences have been shown in schizophrenia brain tissue studies. TNC is expressed in the brain where is involved in the migration of the neurons and axons. In addition, we also used the simulation results to examine whether interactions between genes associated with abnormal emotion/affect behaviour influence risk for psychosis and cognition in humans, in a case-control study of 2049 cases and 1794 controls. Before correcting for multiple testing, significant interactions between CRHR1 and ESR1, and between MAPT and ESR1, and among CRHR1, ESR1 and TOM1L2, and among MAPT, ESR1 and TOM1L2 were observed in abnormal fear/anxiety-related behaviour pathway. There was no evidence for epistasis after Bonferroni correction.

This thesis follows the research portfolio format and is carried out in part fulfilment of the academic component of the Doctorate in Clinical Psychology at the University of Edinburgh. An abstract provides an overview of the entire portfolio thesis. Chapter One contains a systematic review of published research exploring staff attitudes towards computerized cognitive behavior therapy (cCBT). Chapter Two is an empirical study examining a range of potential predictor variables on well-being outcomes from cCBT. Chapter one is prepared for Behavioural and Cognitive Psychotherapy, whereas chapter two is prepared for submission to the journal, Behaviour Research and Therapy. Both chapters follow the relevant author guidelines. Background: Evidence suggests that computerised cognitive behavioural therapy (cCBT) is both effective and efficacious in treating depression and anxiety. Numerous barriers to its implementation and uptake have been identified, however, including attitudinal variables and high patient attrition rates. Research examining predictors of response from cCBT have tended to adopt the pathological model of distress, focussing on symptom reduction rather than the promotion of well-being. Furthermore, exploration of possible predictors has tended to focus on a narrow range of factors (e.g. age, gender), neglecting key psychosocial variables (e.g. social identification, baseline distress) that could be exerting an effect. Aims: A systematic review examined staff attitudes towards cCBT for depression, anxiety, and comorbid depression and anxiety, focussing on three attitudinal domains: Perceived acceptability of cCBT; staff's self-reported intention to use cCBT in the future, and perceived advantages and disadvantages of cCBT for depression and/or anxiety. An experimental study was subsequently conducted, examining a range of potential predictors on well-being outcomes from a cCBT intervention utilising Beating the Blues. Method: A systematic search across five databases was conducted, followed by manual searches. Strict search criteria were applied, resulting in the identification of 15 studies. These were subjected to quality assessment, data extraction and synthesis. For the empirical study, data from 1354 participants was collected, with subgroup-analyses conducted on those completing measures of life and mental health satisfaction, functioning and well-being. Key potential predictors of interest were level of group identification, baseline distress, and socioeconomic deprivation. Results: Findings from the systematic review indicated that staff held relatively positive attitudes towards cCBT, with some ambivalence emerging in relation to perceived advantages and disadvantages of the intervention. The empirical study obtained significant effects of group identification on life and mental health satisfaction. A mediating impact of group identity on baseline distress emerged, whereas a moderating effect of baseline distress on deprivation was obtained for the functioning model. Discussion: The current findings demonstrated both positive and negative aspects of staff attitudes towards cCBT for depression and/or anxiety, whereas the empirical project established a clear link between social identification, baseline distress, and well-being. Results from both studies are discussed in terms of clinical implications relating to the uptake of cCBT.

This thesis is an autoethnographic exploration and articulation of aspects of my lived experience of the longterm impact of professional abuse. It is a context-dependent single case study written from a researcher-participant-counsellor perspective. In my review of the literature I demonstrate the challenges of researching and documenting the direct experiences of women who have been sexually exploited by male professionals. These challenges stem from our natural human tendency to deny traumatic experience, and from the prevailing culture of many social institutions which continues to have the effect of silencing women's voices and discrediting women's experience. The methodological approach I have taken in this thesis is evocative autoethnography. I have chosen this approach in order to document and analyse my present embodied experiences of remembering past abuse, continuing feelings of loss, and unfulfilled longing for resolution and release. I explore the relationship between my past and present selves in context, and consider the therapeutic possibilities of combining memory work, lifewriting, poetry, and imagination to create texts of remembering and re-remembering, to reclaim both what is and what might have been.

This thesis focuses on the trainee counsellor’s experience of speaking a second language in counselling practice. It is based on a single in-depth case study, examining the author’s experience of practice during her training and in her first post-qualification years. Through a detailed exposition of the practitioner’s countertransference experience in relation to her use of a second language, it identifies three positions, termed ‘Worrying and Stumbling’, ‘Connecting and Attuning’ and ‘Relaxing and Playing’. Detailed practice examples are provided to illustrate each position. Like Klein’s use of the term, positions are conceptualised not as chronological or fixed stages, but as ways of being in relation which can dominate or recede at any time. In contrast to the problem-focused perspective that characterises existing research on second language use in counselling, this thesis provides evidence of the opportunities that arise in the therapeutic relationship when the counsellor is working in a second language, even arguing that second language use can be an asset. As counselling and psychotherapy become increasingly globalised, with counsellors and clients often no longer sharing the same native tongues, this thesis makes a timely contribution to research focused on the counsellor’s experience in this setting. Shedding new light on the experience of trainees working in a second language, it offers insights to counselling educators, researchers, practitioners and trainees.

Psychotic disorders represent a severe category of mental disorders affecting about one percent of the population. Individuals experience a loss or distortion of contact with reality alongside other symptoms, many of which are still not adequately managed using existing treatments. While animal models of these disorders could offer insights into these disorders and potential new treatments, translation of this knowledge has so far been poor in terms of informing clinical trials and practice. The aim of this project was to improve our understanding of these pre-clinical studies and identify potential weaknesses underlying translational failure. I carried out a systematic search of the literature to provide an unbiased summary of publications reporting animal models of schizophrenia and other psychotic disorders. From these publications, data were extracted to quantify aspects of the field including reported quality of studies, study characteristics and behavioural outcome data. The latter of these data were then used to calculate estimates of efficacy using random-effects meta-analysis. Having identified 3847 publications of relevance, including 852 different methods used to induce the model, over 359 different outcomes tested in them and almost 946 different treatments reported to be administered. I show that a large proportion of studies use simple pharmacological interventions to induce their models of these disorders, despite the availability of models using other interventions that are arguably of higher translational relevance. I also show that the reported quality of these studies is low, and only 22% of studies report taking measures to reduce the risk of biases such as randomisation and blinding, which has been shown to affect the reliability of results drawn. Through this work it becomes apparent that the literature is incredibly vast for studies looking at animal models of psychotic disorders and that some of the relevant work potentially overlaps with studies describing other conditions. This means that drawing reliable conclusions from these data is affected by what is made available in the literature, how it is reported and identified in a search and the time that it takes to reach these conclusions. I introduce the idea of using computer-assisted tools to overcome one of these problems in the long term. Translation of results from studies looking at animals modelling uniquely-human psychotic disorders to clinical successes might be improved by better reporting of studies including publishing of all work carried out, labelling of studies more uniformly so that it is identifiable, better reporting of study design including improving on reporting of measures taken to reduce the risk of bias and focusing on models with greater validity to the human condition.

A fundamental question in language research is the extent to which linguistic and cognitive systems interact. The aim of this thesis is to explore that relationship across new contexts and over the entire adult lifespan. This work centers on two branches of empirical research: the first is an investigation into the impact of later-life language learning on cognitive ageing (chapters 2-4), and the second examines the cognitive mechanisms underlying communicative perspective-taking from young adulthood into old age (chapter 5). The results of these chapters demonstrate that changes to one's linguistic environment can affect cognitive functions at any age, and similarly age-related changes to cognition can affect linguistic abilities, shedding light on the extent to which language and the brain are intricately connected over the lifespan. In the discussion (chapter 6), I consider how this work contributes new insights to the field, opening the door for future research to explore methods of improving cognitive abilities and linguistic behavior in old age.

Clinical decision-making about psychological interventions is best supported by robust evidence and informed patient choice. Randomised controlled trials (RCTs) are the current gold standard in evaluating intervention effectiveness and identifying harm. At present, RCTs of psychological intervention are unlikely to include measurement of adverse effects and this is in part due to lack of consensus about this topic. A Delphi study was conducted with a panel of both professionals and people with personal experience of face-to-face psychotherapy across the spectrum of mental health difficulties to seek consensus on what to include on a measure of adverse effects. Fifty-four items derived from an initial list of 147 items generated by the panel, are included on the APTMOS outcome measure, which now in it's preliminary form now requires validation before use in RCTs. To date, the evidence for psychological interventions for psychosis and schizophrenia has not been synthesised, which is important to inform patient choice and decision-making. Network meta-analysis compares multiple interventions using direct evidence from randomised controlled trials (RCTs) and indirect evidence from the network. A systematic review of the literature identified 91 RCTs across 23 different intervention/control group categories. Psychological interventions were more effective at reducing total symptoms of psychosis than control groups. One intervention with a low risk of bias, mindfulness-based psychoeducation, was consistently identified as most effective, with large effect sizes. Subgroup analyses identified differential effectiveness in different settings and for different subgroups. Further high quality RCT evidence of the highest ranked interventions is required to inform updates to clinical guidelines of psychological interventions for psychosis.

1H-Magnetic Resonance Spectroscopy (MRS) is a MRI paradigm that allows the levels of specific metabolites to be estimated in vivo [1]. This means that insights into the biochemical changes associated with a rare genetic change that raises the risk of mental disorders, and the impact of having a mental disorder, can potentially be made. In this study the levels of glutamate and N-acetyl-aspartate (NAA) were measured at 3T field strength in three separate voxels: right dorsolateral prefrontal cortex (DLPFC), left DLPFC and the anterior cingulate cortex (ACC). This thesis reports that members of a family that carry a unique t(1;11)(q42.2;q14) translocation that affects DISC1 have a substantially raised risk of developing a range of mental disorders, including bipolar affective disorder, schizophrenia and depression. A genetic change that leads to an increase in the susceptibility to a range of mental disorders is in line with other genetic studies that have been recently reported [2, 3]. The translocation was associated with a significant reduction in right DLPFC glutamate (mean difference= -2.11, CI= -0.24: -3.98, p=0.029) and left DLPFC NAA (mean difference= -1.97, CI= -0.34: -3.61, p=0.020). Changes in these metabolites offer some support to studies in cells and rodents trying to understand the impact of the t(1;11) translocation. More specifically the results offer support to studies that have linked alterations in DISC1's molecular biology to changes in glutamate receptors and mitochondrial function [4-6]. The results need to be interpreted with some caution due to the small sample size and the lack of a significant effect in the bilateral DLPFCs. People with a major mental disorder were also found to have significantly lower levels of glutamate in the left DLPFC (F=3.16, p=0.047). When compared to controls the reductions were significant in the people with a diagnosis of schizophrenia (mean difference= -0.86, CI= -0.19: -1.51, p=0.012), but not in people with bipolar affective disorder. Glutamate levels were significantly correlated with negative symptoms in people with schizophrenia (SANS r= -0.44, CI= -0.07: - 0.70, p= 0.024). The effect of experiencing depressive symptoms was also evaluated due to support for a link in previous studies [7, 8]. Whist the participants were not recruited due their experience of depressive symptoms, metabolite levels were found to be significantly associated with depressive symptoms in all participants with a mental disorder (all three voxels, both NAA and glutamate p < 0.05). The experience of depressive symptoms is not the same experiencing a depressive episode though, and further work may offer more insights into the association between metabolite changes and experience of depression. These findings provide insights into the relationship between diagnosis, current psychopathology and genetic risk in major mental disorders. The thesis provides some support that MRS imaging can be used to try understand neurobiological changes that are associated a genetic change, which is in turn linked to range of mental disorders. Interpreting the results of MRS imaging studies in humans remains challenging due to the complexity of the molecular biology that underpins the estimated metabolite levels, but where there has been a wide range of translational study into a specific protein (or genetic change) MRS may offer further information to help understand any effect in vivo.

Background An increasing body of research is suggesting that childhood trauma and adversity may be associated with various adverse mental health outcomes, including psychosis. Cognitive functioning is often compromised in psychosis, and research has shown that there may be a link between early trauma and cognitive impairment in people with psychosis. No systematic review of the literature of this link has been undertaken, and very few studies have examined samples of individuals at high clinical risk for psychosis, to assess whether the potential link between adversity and cognitive functioning exists, without the confounding factors of length of illness, antipsychotic medication and chronicity of symptoms. Method The systematic review of all relevant electronic databases investigates the research to date on the association between childhood adverse experiences and cognitive ability in psychosis, and the conclusions that can be drawn from the existing literature, taking into account relevant considerations regarding sample, methodology and statistical analysis. The subsequent empirical study utilizes a sample at clinical high risk of developing psychosis, and a healthy control group to investigate whether any putative association in specific domains of cognitive functioning, or global cognitive ability and childhood adversity exist in those at clinical high risk, compared to controls. Results The systematic review indicated that at present, the literature looking into childhood adversity and cognitive ability in relation to psychosis is heterogeneous, with some studies finding that this association only occurs in patients, whilst others suggest it only occurs in the control groups. Some studies found it to be specific to certain cognitive domains, whilst others suggest it was a more global impairment. Methodology, samples and analysis differed considerably across studies, and likely contribute to the heterogeneity of the literature. The empirical paper showed a significant interaction effect between group (high risk versus controls) in the high childhood adversity group, in relation to global cognitive ability. Interestingly, this was not related to psychotic symptom severity or distress. Conclusion Several limitations of the existing studies limit the conclusions that can be drawn from the existing evidence regarding the link between childhood adversity and cognitive ability, and future research in prodromal samples is essential. The empirical study showed that there is a link between childhood adversity and cognitive ability in those at clinical high risk of developing psychosis, before disorder onset, that is not present in controls. This suggests that this may form a vulnerability in those at high risk for psychosis, rather than a more general mechanism present in the typical population.

Human population-based studies have shown that cognitive ability and negative emotions are associated with later health outcomes. Part of this association might be due to shared genetic influences. The present thesis has two main objectives. The first is to examine the shared genetic aetiology between cognitive ability and mental and physical health. The second is to examine the shared genetic aetiology between the tendency to experience negative emotions and mental and physical health. Chapter 1 and Chapter 2 provide an introductory overview of the field of individual differences in psychology, with the first Chapter focussing on cognitive ability and the second on personality (especially neuroticism). Each of these Chapters provide an historical overview of the two traits, followed by the associations with health outcomes, and finish by exploring the genetic aetiology of both cognitive ability and negative emotions and the potential genetic overlap with health outcomes. Chapter 3 focusses on the main cohort analysed in this thesis, the UK Biobank. This Chapter outlines the study population and its demographics, and provides a detailed account of the main variables examined in this thesis. Chapters 4 to 7 present the empirical work and are split in two parts; the first part (Chapters 4 and 5), focusses on cognitive ability. The second part (Chapters 6 and 7) focusses on negative emotions. Chapter 4 presents two studies, examining the shared genetic aetiology between cognitive ability and mental and physical health using linkage disequilibrium score regression and polygenic profile analysis; Mendelian Randomization is used to test for direction of effect between cognitive ability and physical health. The results indicate a substantially shared genetic aetiology between cognitive ability and both physical and mental health. No evidence was found for a causal association between cognitive ability and physical health. Chapter 5 examines the genetic aetiology of a test of executive cognitive function, the Trail- Making test, which has been closely associated with other cognitive abilities. This Chapter also examines the shared genetic aetiology between the Trail-Making test, general cognitive ability, processing speed, and memory, using a range of molecular genetic techniques. The results provide heritability estimates ranging from 7% to 22% for the different Trail-Making test measures, and there are new genetic associations with the Trail-Making test. A considerable degree of genetic overlap is found between the Trail-Making test and general cognitive function and processing speed in particular. Chapter 6 explores the shared genetic aetiology between the personality trait of neuroticism and mental and physical health using Linkage Disequilibrium Score Regression and polygenic profile analysis. The results show significant genetic correlations between neuroticism and major depressive disorder, schizophrenia, and anorexia. Polygenic profile scores for multiple mental health traits, as well as body mass index, coronary artery disease, and smoking status are predictive of neuroticism. Chapter 7 examines the genetic contributions to self-reported tiredness, a trait strongly related to the tendency to experience negative emotions; it also examines the genetic overlap with health outcomes using Linkage Disequilibrium Score Regression and polygenic profile analysis. The results demonstrate a significant heritability estimate of 8% for self-reported tiredness. Extensive genetic overlap is identified between self-reported tiredness and mental and physical health, and particularly with the trait of neuroticism. Finally, Chapter 8 summarizes the empirical findings presented in Chapters 4 to 7. This Chapter discusses limitations of the methods used in this thesis, and offers suggestions for future research in the field of genetic epidemiology, especially as applied to health and psychological differences.

Background There now exist a range of efficacious options for the treatment of psychosis in mental healthcare. The importance of recovery, empowerment, dignity and choice among patients with severe mental health diagnoses are important topics in contemporary research and practice. This thesis presents a meta-analytic review followed by a randomised controlled experimental study. These address distinct but related questions which aim to further our understanding of the choices available for intervention in psychosis and whether intervention may improve the ability of psychosis patients to make those choices. Aims The first objective aimed to offer a comprehensive review of the effectiveness of social skills training (SST), which is a psychological intervention for psychosis. SST has fallen out of favour in the UK and is not widely implemented in practice. We hypothesised that SST would demonstrate superiority for the negative symptoms of psychosis. The second objective was to determine whether decision-making capacity regarding treatment among psychosis patients could be improved by the application of a brief psycho-educational intervention targeting the jumping-to-conclusions (JTC) bias, which is a commonly observed cognitive bias in psychosis. We hypothesised that the intervention would improve decision-making capacity. Methods Firstly, a series of 70 meta-analyses are presented in a systematic review assessing the efficacy of social skills training across a number of psychosis outcome domains: positive symptoms, negative symptoms, general symptoms, overall symptoms and social functioning outcomes. Secondly, a randomised controlled experimental study is presented in which 36 psychosis patients in NHS Lanarkshire and 1 in NHS Dumfries & Galloway were allocated to receive either a brief meta-cognitive training (MCT) intervention or an non-specific control presentation lecture. Capacity was assessed at baseline and post-treatment while the impact of the intervention upon capacity was estimated by ANCOVA. Mediation analyses assessed whether changes in the JTC bias mediated outcome. Findings In the meta-analytic review, SST demonstrated superiority over treatment as usual (TAU. g=0.3), active controls (g=0.2-0.3) and comparators pooled (g=0.2- 0.3) for negative symptoms; and over TAU (g=0.4) and comparators pooled (g=0.3) for general psychopathology. In the randomised controlled study, MCT demonstrated large effects on two capacity outcomes; overall capacity (d=0.96, p < .05) and appreciation (d=0.87, p < .05). Exploratory analyses suggested a mediating effect of JTC (d=0.64, p < .05). Interpretation SST demonstrates a magnitude of effect for negative symptoms similar to those commonly reported for CBT for positive symptoms and may have potential for wider implementation in mental healthcare settings. The randomised controlled study suggests that psycho-educational interventions targeting capacity have clinical utility and may be developed for implementation. Limitations included lack of blinding, no fidelity checks and inclusion based on clinical diagnosis therefore a larger randomised controlled trial addressing these limitations is warranted.

Background: With advances in medical treatments, the numbers of cancer survivors have grown considerably over recent years. Following completion of cancer treatment, patients can experience a range of physical and psychological difficulties, particularly around critical transition phases such as adjustment to survivorship. One of the most common difficulties cited by cancer survivors is that of fear of cancer recurrence (FOR). Existing treatments for improving psychological wellbeing in this population appear to offer limited efficacy, and there are very few interventions directly targeting FOR. Acceptance-based approaches, with an underlying aim of improving psychological flexibility, offer one novel alternative approach to addressing these difficulties. Methods: This thesis presents a systematic review and meta-analysis of the literature in relation to the effectiveness of acceptance-based interventions for post treatment cancer survivors, with a particular focus on Mindfulness-Based Interventions (MBI). A cross sectional questionnaire study is then reported which explores the potential role of psychological flexibility in mediating the relationship between FOR and distress and quality of life (QoL)outcomes. Results: The findings of the review offer tentative support for the effectiveness of MBI in reducing stress and depressive symptoms, while less convincing results emerged for anxiety. Results from the empirical study suggest that while psychological flexibility does not appear to significantly mediate the impact of FOR on distress and QoL, value based living and cognitive fusion did emerge as significant mediating variables within these relationships. Conclusions: Findings suggest that acceptance-based approaches, may be of benefit in reducing the burden of distress and improving the lives of cancer survivors. Supporting cancer survivors to become less entangled with their thoughts and live in accordance with their values may be particularly beneficial. Further studies using larger samples and longitudinal designs are warranted.

This thesis investigated treatment outcomes and processes in young people with chronic pain. The first chapter describes a systematic review, which examined the effectiveness of acceptance and mindfulness-based interventions in improving pain-related outcomes in young people. Secondary aims were to review changes in proposed treatment processes following the interventions, and to compare the effectiveness of these interventions to control conditions. Although there was evidence to suggest that these treatments may improve outcomes, particularly levels of daily functioning, further research is needed to adequately assess the utility of acceptance and mindfulness-based approaches with paediatric chronic pain populations. The second chapter details a cross-sectional study of contextual and cognitive processes in adolescents with chronic pain. Specifically, the study tested the mediating effects of acceptance, catastrophising and kinesiophobia in the relationship between pain intensity and indicators of adjustment. Both acceptance and kinesiophobia mediated the effects of pain intensity on disability and quality of life, while catastrophising mediated the effect of pain intensity on levels of anxiety and depression. The results demonstrated that both contextual and cognitive factors are important determinants of young people’s well-being. Future research would benefit from gaining a greater understanding of how these processes interact with each other to affect pain-related outcomes.

Mental time travel (MTT) refers to an individual’s ability to mentally travel through subjective time, autonoetically re-experiencing past events under the form of autobiographical memories (past MTT), and pre-experiencing events as future autobiographical representations (future MTT). MTT can occur voluntarily, whereby a past/future autobiographical event is subjectively experienced as an intended occurrence, or involuntarily, wherein such an event is subjectively experienced as an unintended outcome of which the individual is aware. Studies investigating MTT’s characteristics in dysphoria and depression show that dysphoric and depressed individuals produce more overgeneral and negative MTT events when compared to control groups. However, existing research has been limited to past and voluntary MTT events, with few studies investigating involuntary MTT and future MTT in dysphoria and depression. The overarching aim of the present research was to compare the phenomenological characteristics of MTT in dysphoric individuals vs. normal mood individuals (Study 1), and in clinically depressed individuals vs. never-depressed individuals (Study 2), with the purpose of furthering existing knowledge on MTT and its relation with dysphoria and Major Depressive Disorder. This aim was addressed by conducting two studies, using a 2 x (2 x 2) mixed-factorial design, with temporality (past vs. future events) and type of retrieval (voluntary vs. involuntary events) as within-subjects independent variables, and participant group as a between-subjects variable. In Study 1, Portuguese university students were categorised into a dysphoric (n=17) or a normal mood group (n=39) depending on their score on the Beck Depression Inventory (BDI-IA) – cutoff point (≥ 10). In Study 2, clinically diagnosed depressed patients (n=32) were recruited from a Portuguese hospital and matched for age and gender with never-depressed control participants (n=32) recruited from the community. The dependent variables tested were: level of spatiotemporal specificity, self-relevance, mood and physical impact, valence, and visual perspective of the MTT events produced. A diary methodology was used in both studies, with an open-ended time period that lasted for a minimum of two weeks, for participants to record their MTT events and grade them on the above mentioned variables using Likert-type ratings. Between seven and fourteen MTT events were produced for each of the four MTT conditions (past voluntary, past involuntary, future voluntary, future involuntary). Results showed that when compared to their respective control groups, depressed, but not dysphoric participants, exhibited a clear influence of mood on several of the phenomenological characteristics of MTT. In Study 1 there were no statistically significant differences in the specificity, negative valence, and mood/physical impact of the MTT events produced by dysphoric and normal mood participants. On the contrary, in Study 2, results partially supported a lower specificity and fully supported a greater negativity and mood/physical impact of MTT events in depressed individuals compared with never-depressed participants. Both studies supported the greater self-relevance of voluntary MTT events and partially supported the hypothesised effect of type of retrieval in specificity. These were the first studies to directly compare past and future, voluntary and involuntary MTT events in dysphoric and depressed individuals, addressing existing gaps in the literature. The key limitation is the relatively small sample size of both studies, however each participant was comprehensively assessed for at least two weeks, providing a rich set of reliable data. Despite limitations, this thesis provides novel pilot findings that help understand the similarities and differences between involuntary and voluntary, past and future MTT, as well as providing new information regarding the possible role of MTT in dysphoria and depression.

Purpose: A systematic review and meta-analysis was conducted to test key predictions of the widely-studied ‘paranoia as defence’ model (more formally known as the ‘attribution–self-representation cycle’) proposed by Bentall, Corcoran, Howard, Blackwood, and Kinderman (2001), as applied to people with psychosis with persecutory delusions. A novel case series was also conducted to examine the feasibility and acceptability of collaborative psychological assessment and formulation of impaired treatment decision-making capacity (TDMC) among patients with psychosis, and produce preliminary data on safety and efficacy. Methods: With regard to the systematic review and meta-analysis, people with psychosis with persecutory delusions were compared to healthy controls, people with depression and people with psychosis without persecutory delusions (and, if specified, grandiose delusions) on a number of outcomes: externalising attributional bias, explicit self-esteem, implicit self-esteem and discrepancy between implicit and explicit self-esteem. Correlations between paranoia severity and each of these outcomes and self-esteem instability were also examined. In regards to the case series, a formulation of impaired TDMC for 5 patient participants was developed and shared with 13 clinician participants. Acceptability, utility, working alliance and safety were assessed through pre and post self-report and interview measures. Results: Sixty-three studies were included in the meta-analysis and systematic review, of which 33, 36, 10, 10 and 4 were used to test hypotheses on externalising attributional bias, explicit self-esteem, implicit self-esteem, implicit-explicit self-esteem discrepancy and selfesteem instability, respectively. Key model-consistent findings included the following: people with psychosis with persecutory delusions had a greater externalising attributional bias compared to all the other groups and a greater implicit-explicit self-esteem discrepancy than people with depression, and paranoia severity was positively correlated with externalising attributional bias and self-esteem instability. Key model-inconsistent findings included the following: people with psychosis with persecutory delusions had lower explicit self-esteem than healthy controls, and paranoia severity was negatively correlated with explicit self-esteem. There were also some model-inconclusive findings. Regarding the case series, 3 of the patient participants collaborated in the development of their formulation. They found the intervention safe and acceptable, following which they provided a much richer understanding of the factors that may impair their TDMC (Cohen’s d = 2.16). Two patient participants only partially adhered to the intervention protocol, but a psychological formulation was still feasible to produce and no adverse effects were reported. Clinician participants provided a much richer understanding of the factors that may impair the patient participants’ TDMC (Cohen’s d = 1.36; 95% CI = 0.63 to 2.07) after the presentation of the case formulations. Increases in knowledge, confidence and positive attitudes regarding supporting the TDMC of patients were observed. They strongly believed that the formulations cohered with their knowledge of the patient participants and were comprehensive and accurate. Conclusions: The findings of the systematic review and meta-analysis support a ‘weak’ version of the paranoia as defence model, which suggests persecutory delusions are only partially effective at protecting low implicit self-esteem from reaching awareness. The findings of the case series suggest that patients with psychosis, and their clinicians, can be engaged in a collaborative psychological assessment and formulation of factors that may impair their TDMC. Initial data from the case series also suggests this process is acceptable, safe and helpful.

Introduction: Poor insight is included as a risk factor for violence in risk assessment tools such as the Historical Clinical Risk-Management-20 version 3 (HCR-20v3) yet there is a lack of consensus around the relationship between poor insight and violence in individuals with psychosis. A systematic literature review was therefore carried out to clarify this relationship. Relatedly, a research project aimed to outline the predictive validity of the HCR-20v3 total and sub-scale scores to violence in forensic inpatients. A secondary aim was to understand the predictive ability of 2 dynamic risk factors within the HCR-20v3 clinical sub-scale; insight and positive symptoms, alongside age and history of violence in relation to violence in psychosis. Method: A systematic search of studies investigating insight and violence in patients with psychosis, published between 1980 and 2016 was carried out on relevant databases.17 articles from combined search results of 5694, met the inclusion criteria. These were selected for full-text review and quality grading which was subject to inter-rater reliability. In the research project, the predictive validity of the HCR-20v3 to violence was assessed in N=167 forensic inpatients. A sub-sample of N=135 was then used to investigate insight, positive symptoms, age and history of violence in relation to violence. Data was extracted from case files, with the exception of violence data which was collected prospectively from date of HCR-20v3 publication via DATIX. Results: The systematic review found 8 studies in support of a positive relationship between poor insight and violence, whilst 9 studies did not support this relationship. The majority of better quality studies measured the clinical insight dimension which tended to demonstrate a positive relationship between poor insight and violence. Methodological limitations were apparent across studies. The research project found HCR-20v3 total and clinical and risk-management sub-scale scores to predict violence. The clinical sub-scale was the strongest predictor of violence and physical violence specifically. Sub-sample analysis found positive symptoms and history of violence to significantly predict violence generally whilst only positive symptoms demonstrated prediction of physical violence. Insight and age were not significantly associated with either violence type. Discussion: The systematic review found partial support for a positive relationship between poor insight and violence in psychosis. Future good quality research is required to develop a fuller understanding of this issue. Research project results support the use of the HCR-20v3 in the risk assessment and management of forensic inpatients. They reinforce the usefulness of dynamic risk factors within the clinical sub-scale in particular. In line with the majority of studies within the systematic review however, a relationship between insight and violence in a sub-sample of patients with psychosis was not found. Recommendations are made for the regular re-assessment of dynamic risk factors within the HCR-20v3 clinical sub-scale in order to support patients to reduce their level of risk, with the caveat that future research is still required to support a relationship between insight and violence in this patient group.

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.

Background: Maltreated children, including those who are looked after away from home, are amongst the most vulnerable members of society. Due to the relational trauma that most looked after children have experienced they are at increased risk of attachment and mental health difficulties, which can impede their ability to form close relationships with new carers. Indeed, many such children behave in ways that fail to elicit caregiving or even as if they do not need caregivers, and providing sensitive, therapeutic care to these vulnerable children can be a considerable challenge. Aims: The aims of this thesis were threefold: to review the impact of maltreatment experiences on children’s executive functioning, to investigate the prevalence of attachment and trauma-related difficulties in children in foster care, and their impact on the parenting task of foster carers. Methods: Aims are addressed in two journal articles. To address the first aim, a systematic review of research regarding the association between maltreatment and executive function in children and adolescents is presented in journal article one. Subsequent aims are addressed in journal article two, a cross-sectional study with foster carers of children in care aged 3-12 years who completed self-report measures investigating the emotional, behavioural, attachment and trauma related difficulties of their foster child, the perceived quality of the relationship, and levels of parenting stress and sense of competence. Results: The systematic review revealed that the majority of studies demonstrated a significant impairment in one or more areas of executive ability in maltreated children, with particular support for impairments in inhibitory control, executive working memory and decision making. However, there was only limited support for impairments in cognitive flexibility, planning/problem solving, and fluency. Furthermore, there was considerable variability between studies in the specific deficits reported. Results from the empirical study highlight the prevalence of attachment and trauma-related difficulties in children in foster care. Hierarchical regression analyses revealed that levels of foster carer-rated inhibited attachment behaviour was a significant predictor of quality of the foster carer-child relationship and parenting stress. The level of emotional and behavioural difficulties also emerged as a significant predictor of quality of the foster carer-child relationship, and parenting sense of competence. Conclusions: This thesis highlights the pervasive impact of relational trauma on children. Results of the systematic review indicate its impact on children’s executive ability. The empirical study reveals the high prevalence of attachment and trauma-related difficulties in children in foster care, and provides insight into factors related to quality of the foster carer-child relationship, and the stress and sense of competence of foster carers. Implications for interventions and service provision regarding maltreated children who become looked after away from home, and their carers, are discussed.

Purpose: The systematic review summarised the literature on the impact of patient illness perceptions on health outcomes and coping after an acute neurological event, guided by Leventhal’s Self-Regulatory Model (SRM). The empirical study investigated individuals’ lived experiences of emotionalism, a sudden onset neurological disorder characterised by involuntary laughter and crying. A further aim was to develop a questionnaire measuring beliefs about emotionalism based on patients’ perspectives. Method: The review identified seventeen articles through database searches using predefined inclusion criteria. In the empirical paper, eighteen individuals took part in a qualitative study to explore their experiences of emotionalism. Results: Findings provided support for the SRM in acute neurological populations. Negative illness perceptions were associated with a range of poor health outcomes and unhelpful coping behaviours. The empirical paper provided rich individual accounts of the social and personal impact of emotionalism. Four themes were identified and used to develop a questionnaire measuring beliefs about emotionalism. Conclusions: Both chapters emphasise the value of eliciting patient beliefs about their neurological condition and of providing support at the early stages of recovery. The clinical implications and directions for future research were discussed as was the need for further validation of the questionnaire.

Background: Stress and burnout is often reported within the ‘human service’ professions. A systematic review aimed to ascertain the prevalence of stress and burnout within clinical psychologists, and the coping strategies utilised by members of this profession. Specifically, the role of clinical psychologists that work with people with intellectual disabilities and behaviour that challenges may, arguably, be particularly challenging, given the risks inherent in behaviour that challenges. Previous work has found that paid and family carers for this population experience substantial levels of stress. However, little is known about the experiences of clinical psychologists who may play a pivotal role in the multi-disciplinary team supporting individuals and their carers. Methods: The systematic review explores the prevalence of stress, burnout and coping in clinical psychologists. An electronic review and hand search of the literature was completed. The quality of all eligible articles was assessed, and themes within the findings were discussed using a narrative synthesis approach. The subsequent empirical article explores the perspectives of 14 female clinical psychologists. Thematic analysis was utilised to derive themes from their interview transcripts. Results: Eight studies met inclusion criteria for the review; findings suggest that a large proportion of clinical psychologists experience symptoms of stress and burnout. Nevertheless, most psychologists also experience high levels of personal achievement in their role. Within the empirical study, two overarching themes were apparent across participants. These included difficult and positive experiences. Participants reported barriers to influencing change and feelings of stress, worry, anxiety, self-doubt and frustration within the role. However, supervision and support from colleagues appeared to moderate difficult emotions. All conveyed a sense of reward within their role. Conclusions: Comparable to other ‘human service’ professionals, clinical psychologists experience symptoms of stress and burnout. With regard to clinical psychologists working with people with intellectual disabilities and behaviour that challenges, it appears that supervision and support from colleagues is key in managing difficult emotions. Based on the findings, provisions that are believed to improve clinical psychologists’ experiences are considered.

Background: Acceptance and Commitment Therapy (ACT) has shown promise as an effective intervention in the treatment of mental health disorders. In the last decade, the delivery of ACT has expanded to include various formats (e.g. groups, self-help, online and phone apps). Further research is needed to evaluate whether such delivery formats are a viable extension of ACT. Furthermore, the existing evidence base of certain alternative delivery formats have yet to be reviewed. This thesis portfolio sought to contribute to this area of research. Methods: A systematic review of the literature was conducted to investigate the efficacy of group-based interventions for mental health disorders using ACT. Five databases were systematically searched, manual searches were conducted and corresponding authors were contacted. Studies which used a randomised-controlled design, with adult samples and investigated group-based ACT interventions for mental health disorders were included. A meta-analysis of the included studies was conducted for post-intervention and follow-up data. In the empirical study, an ACT manual was trialled using a randomised-controlled design to investigate the efficacy of using ACT in a guided self-help context. Participants with anxiety/depression were randomly assigned to receive either the ACT intervention or treatment as usual (TAU). Those in the ACT group were posted an ACT manual and received two telephone calls. Outcome measures were analysed after the six-week intervention. Results: From the meta-analysis, 18 randomised-controlled trials were identified, 14 of which focussed on anxiety and depression. The findings suggest that ACT-based groups have a large effect on symptom reduction when compared to non-active comparisons at post-treatment and a moderate effect when compared to non-active comparisons at follow-up. Additionally, there was a small effect in favour of ACT when compared to active treatment controls at post-treatment and equivalent effects when comparing ACT to active treatment controls at follow-up. Similar effects were found when separately comparing the 14 studies which focussed primarily on anxiety and depression. The empirical study revealed that guided self-help was found to be no more effective in improving quality of life or reducing psychological distress than the TAU group. However, such results should be interpreted with caution as the small sample size and high attrition rate indicates that further research with larger samples and follow-up are needed before strong conclusions can be made. Conclusions: The findings of this research indicate that group-based ACT interventions may be a suitable alternative delivery format for service providers in the provision of common mental health disorders, particularly anxiety and depression. Further research is needed before any strong conclusions can be made regarding the efficacy of guided self-help for anxiety/depression.

Introduction: This research portfolio set out to examine service user defined recovery in psychosis. A systematic review was undertaken to examine the evidence-base for the effectiveness of psychosocial interventions on personal recovery, empowerment and other recovery-related outcomes. An empirical study was conducted to examine the relationships between self-stigma, decisional capacity for treatment and personal recovery in service users with psychosis. Methods: A review of published literature identified ten randomised controlled trials investigating the effects of psychosocial interventions on personal recovery. A narrative synthesis was reported for findings relating to primary and secondary outcomes, and standardised effect sizes were calculated to quantify within-group change from pre-to post-intervention and follow-up. Studies were assessed for risk of bias. The empirical study recruited twenty-four participants with diagnoses of non-affective psychosis. Semi-structured interviews and self-report measures were administered to assess self-stigma, decisional capacity for treatment, psychopathology, emotional distress and personal recovery. Results: A small number of studies found that recovery-focused psychosocial interventions improved personal recovery. There were more consistent effects on psychiatric symptoms, functioning and depression. The empirical study found that self-stigma and personal recovery were associated with each other. Large effect sizes were found for the associations between self-stigma and symptoms. These associations persisted when controlling for personal recovery scores. Understanding of treatment was predicted by excitement symptoms, but no other prediction model emerged for decisional capacity. Conclusion: Taken together, the systematic review and empirical project support service user definitions of recovery which highlight the role of psychosocial factors. The systematic review found some evidence for the role of recovery-focused psychosocial interventions in improving personal recovery. Further research is needed so that interventions specifically targeting the processes in personal recovery can be developed. The findings from the empirical project suggested that interventions designed to overcome self-stigmatising beliefs and reduce emotional distress are likely to improve personal recovery outcomes in psychosis. More research is needed to develop a broader conceptualisation of decisional capacity in psychosis, to support the active participation of service users in their recovery journey.

Background: Previous research has reported positive correlations between perfectionism, anxiety and depression within community adolescent samples. Psychological distress has the potential to develop into adulthood; therefore consideration is required about potential mechanisms that could positively impact on this trajectory. Self-compassion has been shown to be negatively associated with psychopathology and positively related to psychological well-being. It has also been found to be inversely related to maladaptive perfectionism (negative aspects of perfectionism) in adult populations. No previous studies have examined both constructs of perfectionism and self-compassion in an adolescent population and what impact they may have on psychological distress and well-being. Aims: This research had two aims: 1. Conduct a systematic literature review exploring the relationship between perfectionism and anxiety/stress in young people; 2. Establish empirically whether perfectionism and self-compassion have a role in the prediction of psychological distress and psychological well-being in an adolescent population. Method: For the first aim a systematic review of the literature was conducted to identify studies that explored the relationships between perfectionism and anxiety/stress in young people. Fourteen papers were identified which were subsequently subjected to methodological appraisal using quality criteria. To address the second aim an empirical study was conducted. It was a cross-sectional, quantitative design using self-report surveys, in an adolescent population (n=128; 64.1% female, mean age 16.24 years) across schools in Edinburgh. Results: The results of the systematic review suggested that there is a significant relationship between perfectionism and anxiety and/or stress in young people; however, some inconsistent results were found between the perfectionism subtypes and their impact on anxiety. Methodologically, the studies held good internal validity, but external validity was poor meaning that the ability to generalise findings beyond the remit of the studies was questionable. The results of the empirical study demonstrated a significant relationship between perfectionism and self-compassion and a subsequent relationship with psychological distress and psychological well-being in the adolescent population. An interaction effect between perfectionism and self-compassion was also established for some of the variables, with self-compassion playing a particularly significant role in this relationship. Conclusions: Overall, there is evidence to suggest a link between perfectionism and psychopathology in adolescents. The factors of perfectionism and self-compassion demonstrated a significant relationship, with both constructs having an impact on psychological well-being in particular. Self-compassion demonstrated a strong predictive relationship to both psychological distress and psychological well-being. The significant findings regarding self-compassion in particular suggest that it may be a potential strategy for working with young people (either clinically or in academic settings) who experience psychological distress related to perfectionistic tendencies. Further research exploring perfectionism and self-compassion and the link with psychopathology in adolescents is much needed. In particular, studies are required which attempt to focus on this area with alternative designs (non cross-sectional), different methodologies and various clinical and non-clinical adolescent populations.

In a large Scottish family a high incidence of schizophrenia, bipolar disorder and major depressive disorder co-segregates with a balanced autosomal translocation (t(1;11)(q42.1;q14.3). The translocation disrupts Disrupted-in-Schizophrenia-1 (DISC1) and DISC2 on chromosome 1, and DISC1FP1 (Disrupted-in-Schizophrenia-Fusion-Partner-1), also known as Boymaw, on chromosome 11. DISC1 is a leading candidate gene for major mental illness and is involved in neurodevelopment and cellular signalling, whilst DISC2 and DISC1FP1 are apparently non-coding RNA genes that undergo alternative splicing and that are expressed in the brain. This thesis aimed to investigate putative mechanisms of pathogenesis that may result from the t(1;11), with the hope that pathogenic mechanisms identified in the t(1;11) pedigree might shed light upon mechanisms conferring risk for psychiatric illness in the wider population. Previous work had identified DISC1/DISC1FP1 chimeric transcripts in t(1;11)-family derived lymphoblastoid cell lines. The detected transcripts include CP60 and CP69 which encode DISC1 aa1-597 plus an additional 60 or 69 amino acids from DISC1FP1, respectively. In this thesis a novel DISC1/DISC1FP1 transcript, CP1, was identified in t(1;11) lymphoblastoid cell lines. The CP1 transcript encodes DISC1 aa1-597 plus one glycine. A truncated form of DISC1 comprising aa1-597 was previously suggested to be a putative product of the translocation and, as such, has been the focus of multiple studies. The identification of the CP1 species is of interest as it differs from DISC1 aa1-597, by only a glycine. As glycines are simple uncharged aa’s, it is likely that these two DISC species share similar properties. In vitro exogenous expression of the three DISC1/DISC1FP1 protein species in both COS-7 and primary neuron cultures revealed contrasting cellular phenotypes. CP1 showed a diffuse cellular localisation pattern with cells containing readily visible tubular mitochondria. This is indistinguishable from the staining pattern of DISC1 aa1-597, highlighting the high degree of similarity between these species. CP60 and CP69, however, appeared to be clustered in the perinuclear region of the cell. Initial staining attempts with MitoTracker Red to visualise mitochondria in CP60 and CP69 expressing cells resulted in fewer than 30% of cells being stained. In those that did stain, the mitochondria appeared clustered. The absence of MitoTracker Red staining in mitochondria may be due to the loss of the mitochondrial membrane potential, Δψm. The adoption of a co-staining protocol with antibodies for mitochondrial proteins enabled the visualisation of mitochondrial structure in all of the cells exogenously expressing CP60 and CP69. All of these mitochondria possessed a clustered morphology, with which CP60 and CP69 expression was substantially co-localised. To see if MitoTracker staining was perturbed, in t(1;11) lymphoblastoid cell lines, as may occur if the DISC1/DISC1FP1 chimeras are expressed endogenously, the fluorescence of MitoTracker Red staining was investigated by FACS. Pooled analysis of experimental replicates revealed a negative result, with MitoTracker Red staining in t(1;11) lymphoblastoid cell lines not differing from controls. These findings indicate a need for further research using the mitochondrial membrane potential, Δψm as a metric as this would enable variations in mitochondrial mass to be accounted for. Prior to my arrival, an expression microarray had been carried out on lymphoblastoid cell line cDNA to assess gene expression differences resulting from the t(1;11). In order to identify putative pathogenic mechanisms, I carried out functional enrichment analysis of the expression array data using multiple analysis programs. Several programs detected dysregulation of the cell cycle and enrichment of altered expression of genes involved in the immune response and inflammation in t(1;11) carriers. The use of a rare variant investigative paradigm in this thesis furthers understanding of the putative pathogenic mechanisms that might act to increase risk for psychiatric illness in t(1;11) carriers. Moreover, it may aid the biological understanding of the aetiology of psychiatric illness in the general population. As such, improved understanding of the mechanisms of risk in the t(1;11) pedigree may eventually lead to the development of better treatments. In the intervening time since some of the research for thesis was published, two studies have emerged that may serve to highlight potential mechanisms of pathogenic action mediated by CP60 and CP69 expression. It has recently been observed that WT-DISC1 couples to the adaptor protein TRAK1 and the mitochondrial membrane anchor Miro1, which are part of the mitochondrial transport complex (Ogawa et al, 2014; Norkett et al, 2016). Furthermore, the exogenous expression of CP60 impairs bidirectional mitochondrial trafficking (Norkett et al, 2016). This suggests that CP60 expression may impair interactions with TRAK1 and Miro1. Given the sequence homology between CP60 and CP69, mitochondrial transport deficits also likely arise with CP69 expression. It is therefore possible that the exogenously expressed CP60 and CP69 proteins could be docked on stationary mitochondria, which may contribute to the clustered expression patterns observed.

A key feature of many psychiatric disorders, including schizophrenia and bipolar disorder, are pervasive deficits in several domains of cognition. Episodic memory is one of the most consistently observed cognitive deficits exhibited by patients with schizophrenia, and can be a predictor of overall functional outcome. Several neuroimaging studies have assessed episodic memory in psychosis, however the neural mechanisms underlying this deficit remain somewhat unclear. Studying the impact of rare genetic variants of large effect can offer a powerful method to further our understanding of the pathophysiology of psychiatric disorders. One such gene, DISC1 (Disrupted in Schizophrenia 1) is a putative susceptibility gene for a spectrum of major psychiatric disorders such as schizophrenia, bipolar disorder and major depression. DISC1 was originally identified in a large Scottish pedigree, in which it is disrupted by a balanced translocation between chromosomes 1 and 11, and this translocation confers a dramatically increased risk of major psychiatric disorder. However, the impact of this translocation on brain imaging measures is largely unknown. The rarity of this variation results in small group numbers for analysis, however rare variants are likely to have large neural effects. This thesis offers a unique investigation into the effects of the t(1;11) translocation, by examining fMRI of members of the original Scottish pedigree. Four groups of participants; 19 family members (8 with the translocation, 11 without), 30 patients with schizophrenia, 11 patients with bipolar disorder and 40 healthy controls underwent a functional MRI episodic memory encoding and recognition paradigm. Data processing and statistical analyses were performed using the standard approach in SPM8. The primary aim of this work was to investigate functional activation during episodic memory in individuals with and without the translocation, to examine the impact of the t(1;11) translocation. Analyses were also performed to examine differences between controls and patients with schizophrenia and bipolar disorder, to compare the effects of the translocation to the effects of a having a psychotic illness. During encoding of neutral scenes, translocation carriers showed greater activation of the left posterior cingulate, right fusiform gyrus and right superior frontal gyrus compared to non-carriers. During recognition, carriers showed greater activation in the right fusiform gyrus, left posterior cerebellum, right superior temporal gyrus, left anterior cingulate, right ventrolateral prefrontal cortex (VLPFC) and right dorsolateral prefrontal cortex (DLPFC). For both contrasts, no regions were found to be more active in family members without the translocation when compared to carriers. There were no significant differences between the groups in terms of their performance or reaction time on encoding and recognition conditions. Compared to healthy controls, patients with schizophrenia demonstrated increased activation during encoding in the inferior parietal lobe bilaterally, and decreased activation during recognition in a region encompassing the caudate nucleus and anterior cingulate cortex. Patients with bipolar disorder showed no difference in activation compared to controls during encoding, and increased activation during recognition in a region encompassing the caudate and anterior cingulate, extending to the inferior frontal lobe and insula. There was also a significant difference between patients with schizophrenia and bipolar disorder during recognition, with patients with bipolar disorder again showing increased activation in the caudate extending to the anterior cingulate cortex. These findings support previous research suggesting overactivation of fronto-limbic and striatal structures including the anterior cingulate and caudate in bipolar disorder, with a relative underactivation in schizophrenia. This thesis presents the first evidence of functional alterations during episodic memory in association with the translocation, primarily in fronto-temporal regions. Brain regions that were over activated in translocation carriers have been shown to be involved in memory encoding and recognition, and are known to be affected in patients with major psychiatric disorders and unaffected relatives. Family members with the translocation demonstrated a more similar pattern of activation during recognition to patients with bipolar disorder compared to schizophrenia, perhaps due to the fact that most diagnoses in the carriers were of an affective disorder rather than a schizophrenia-related psychosis. Based on these findings it can be argued that the translocation has an influence on brain activations in areas associated with episodic memory processes. These findings begin to provide a better understanding of the neural effects of the t(1;11) translocation, and highlight the significance of rare but biologically informative genetic variants in understanding psychosis.

Purpose: A systematic review and meta-analysis was conducted to identify what factors have been investigated as correlates of the 4 key domains of treatment decision making capacity (TDMC) in people who have experienced psychosis (understanding, reasoning, appreciation, communication) and to provide estimates of the magnitude of these correlations, taking into account study quality. A novel empirical study was conducted to test the hypothesis that variance in psychosis-specific cognitive biases (including the well-established ‘jumping to conclusions’ bias) would account for unique variance in TDMC domains in those with psychosis, after taking into account the known contribution of symptoms and insight. A secondary aim of the empirical study was to examine for the first time the relationship between TDMC and personal recovery in this group, and post hoc analyses of the relationship between cognitive biases, emotional distress and TDMC were also conducted. Methods: Electronic databases were systematically searched for literature on the schizophrenia and psychosis and treatment decision making capacity. Pooled estimates of correlation were estimated for factors with data from three or more studies, and both study and outcome quality were systematically assessed. A cross-sectional observational study was conducted, and individuals with psychosis completed measures of TDMC, cognitive biases, psychotic symptoms and recovery. Multiple regression was used to examine the primary and secondary hypotheses, and mediation analyses were used to conduct the post hoc analyses. Additional data from a parallel study was incorporated to increase power. Results: Twenty-four studies met inclusion criteria for the systematic review and meta-analysis. Low to moderate quality evidence suggested that the ability of people with psychosis to understand treatment-relevant information was strongly associated with overall psychotic symptom severity, verbal cognitive functioning and years of education, but not depression (moderate quality evidence). Low quality evidence suggested reasoning was strongly associated with verbal cognitive functioning and moderately associated with symptoms. Appreciation was associated with symptoms, but it and communication were generally poorly studied. Findings from the empirical study suggest that cognitive biases, and the Jumping to Conclusions bias in particular, predicts a moderate amount of the variance in the understanding and reasoning TDMC domains, but did not add predictive power to a model containing symptoms, insight, and cognition. The appreciation domain was strongly predicted by cognitive biases, insight, and cognition. TDMC was not found to be correlated with personal recovery and post hoc analyses did not find that emotional distress mediated any relationship between cognitive biases and TDMC. Conclusions: The meta-analysis confirms there is a robust association between symptoms and TDMC in psychosis, as currently conceived. The empirical study suggests cognitive biases may be related to TDMC, even after taking into account the contribution of symptoms. Larger studies, perhaps employing experimental procedures, are required to clarify the exact nature of this relationship. The lack of any relationship between TDMC and service-user defined recovery from psychosis is notable, and lends support to those calling for a conceptualisation of TDMC that takes greater account of this concept.

This thesis is an exploration of values-consistent behaviour from a contextual behavioural science perspective. The first chapter is a systematic review of the effectiveness of acceptance and commitment therapy in enhancing values-consistent behaviour. The results from this review were inconclusive, mainly due to a lack of psychometrically robust outcome measures, and inconsistent use of available measures. Recommendations were made to improve the utility of measures of values-consistent behaviour. The second chapter reports a cross-sectional survey of adolescents, aimed at testing the psychometric properties of values measures, and assessing the relationship between values-consistent behaviour and wellbeing. The measures used in this study were the Valued Living Questionnaire 2 (VLQ-2), Portrait Values Questionnaire – Second Revision, Child and Adolescent Mindfulness Measure, Avoidance and Fusion Questionnaire for Youth – Short Form, and the Warwick-Edinburgh Mental Well-being Scale. Using the VLQ-2 in its current form, values-consistent behaviour was found to account for an additional 13% of variance in wellbeing, above the contributions of demographics, mindfulness and experiential avoidance. However, a recommendation was made for adaptions to be made to the VLQ-2 to make it more suitable for adolescents.