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Schizophrenia is a serious psychiatric disorder characterised by a breakdown in thought, emotion and perception, which leads to alterations of normal behaviour and feelings, a withdrawal from reality and an impression of mental defragmentation. Of the positive, negative and cognitive symptoms, the positive symptoms are perhaps the most striking. However, it is the severity of cognitive deficits that are most closely associated with a patients’ functional outcome in the long-term. Despite this, the successful treatment of the cognitive deficits has been met with difficulty, partly due to a lack of suitable animal models. There is an urgent need for animal models with appropriate face, construct and predictive validity for schizophrenia so that improved drug targets can be identified, and new drugs tested. In 2012, Winchester et al. discovered that sequence variations in the Map2k7 gene were associated with increased risk for schizophrenia, and Map2k7 mRNA was decreased in the prefrontal cortex of the post mortem brains of patients. The primary aim of this thesis is to behaviourally and molecularly characterise mice which are heterozygous for Map2k7 (Map2k7+/- mice) as a potential animal model of relevance to schizophrenia. Sequence variants in the Map2k7 gene are moderately common in the population and they almost double the disease risk (OR~1.9); hence, alterations of the Map2k7 gene in mice represent an ideal basis for an animal model with good construct validity. The Map2k7 gene produces the MKK7 protein, a kinase within the stress-activated JNK pathway, and is involved in a diverse range of cellular processes, such as apoptosis, synaptic plasticity and regulation of the immune response. First and foremost, the components of the MKK7/JNK pathway were quantified in Map2k7+/- mice and MKK7γ was found to be significantly decreased in the prefrontal cortex compared to their wildtype (WT) littermates, a highly disrupted brain region in patients with schizophrenia. Map2k7+/- mice also exhibited behavioural phenotypes relevant to schizophrenia: hyperactivity in the open field and attentional dysfunction. Minocycline showed promise in alleviating the attentional deficits and hyperactivity in the open field, but did not influence protein levels of signalling pathway components. Map2k7+/- mice did not show a decrease in sensorimotor gating as many patients do; however, they exhibited signs of altered response to amphetamine administration just prior to testing of sensorimotor gating, compared to WT mice. Decision-making abilities were also investigated: Map2k7+/- mice showed normal learning and performance of the rodent gambling task. Additionally, all mice were able to alter their choice pattern to be more optimal when the task contingencies were subtly switched, which was the first time this has been shown in mice in the touchscreen apparatus. However, when the task demands were altered such that ‘punishment’ no longer featured as prominently, Map2k7+/- mice showed huge difficulty compared to their WT littermates in shifting their choice pattern to be more optimal, suggesting they have a deficit in aspects of cognitive flexibility. Finally, Map2k7+/- mice were investigated as a gene x environment interaction model, by injecting pregnant dams with Poly I:C and examining the resultant immune response in maternal serum and embryonic brain. Map2k7+/- dams exhibited an altered immune response to Poly I:C compared to WT dams; however, future experiments will be required to confirm whether this altered cytokine response is also present in embryonic brain. Overall, Map2k7+/- mice show utility for dissecting the cognitive deficits and some aspects of the positive symptoms of schizophrenia that could be targeted by novel compounds. This would be aimed at restoring the function of the MKK7/JNK pathway. Further molecular and behavioural characterisation will be required, particularly into the potential gene x environment interaction model. Although no mouse model can recapitulate the full symptom spectrum of a human neuropsychiatric disorder, Map2k7+/- mice exhibit an interesting accumulation of phenotypic abnormalities relevant to schizophrenia.

Traditionally, early visual cortex (V1-3) was thought of as merely a relay centre for feedforward retinal input, providing entry to the cortical visual processing steam. However, in addition to feedforward retinal input, V1 receives a large amount of intracortical information through feedback and lateral connections. Human visual perception is constructed from combining feedforward inputs with these feedback and lateral contributions. Feedback connections allow the visual cortical response to feedforward information to be affected by expectation, knowledge, and context; even at the level of early visual cortex. In Chapter 1 we discuss the feedforward and feedback visual processing streams. We consider historical philosophical and scientific propositions about constructive vision. We introduce modern theories of constructive vision, which suggest that vision is an active process that aims to infer or predict the cause of sensory inputs. We discuss how V1 therefore represents not only retinal input but also high-level effects related to constructive predictive perception. Visual illusions are a ‘side effect’ of constructive and inferential visual perception. For the vast majority of stimulus inputs, integration with context and knowledge facilitates clearer, more veridical perception. In illusion these constructive mechanisms produce incorrect percepts. Illusory effects can be observed in early visual cortex, even when there is no change in the feedforward visual input. We suggest that illusions therefore provide us with a tool to probe feedforward and feedback integration, as they exploit the difference between retinal stimulation and resulting perception. Thus, illusions allow us to see the changes in activation and perception induced only by feedback without changes in feedforward input. We discuss a few specific examples of illusion generation through feedback and the accompanying effects on V1 processing. In Schizophrenia, the integration of feedback and feedforward information is thought to be dysfunctional, with unbalanced contributions of the two sources. This is evidenced by disrupted contextual binding in visual perception and corresponding deficits in contextual illusion perception. We propose that illusions can provide a window into constructive and inferential visual perception in Schizophrenia. Use of illusion paradigms could help elucidate the deficits existing within feedback and feedforward integration. If we can establish clear effects of illusory feedback to V1 in a typical population, we can apply this knowledge to clinical subjects to observe the differences in feedback and feedforward information. Chapter 2 describes a behavioural study of the rubber hand illusion. We probe how multimodal illusory experience arises under varying reliabilities of visuotactile feedforward input. We recorded Likert ratings of illusion experience from subjects, after their hidden hand was stimulated either synchronously or asynchronously with a visible rubber hand (200, 300, 400, or 600ms visuotactile asynchronicity). We used two groups, assessed by a questionnaire measuring a subject’s risk of developing Schizophrenia - moderate/high scorers and a control group of zero-scorers. We therefore consider how schizotypal symptoms contribute to rubber hand illusory experience and interact with visuotactile reliability. Our results reveal that the impact of feedforward information on higher level illusory body schema is modulated by its reliability. Less reliable feedforward inputs (increasing asynchronicity) reduce illusion perception. Our data suggests that some illusions may not be affected on a spectrum of schizotypal traits but only in the full schizophrenic disorder, as we found no effect of group on illusion perception. In Chapter 3 we present an fMRI investigation of the rubber hand illusion in typical participants. Cortical feedback allows information about other modalities and about cognitive states to be represented at the level of V1. Using a multimodal illusion, we investigated whether crossmodal and illusory states could be represented in early visual cortex in the absence of differential visual input. We found increased BOLD activity in motion area V5 and global V1 when the feedforward tactile information and the illusory outcome were incoherent (for example when the subject was experiencing the illusion during asynchronous stimulation). This is suggestive of increased predictive error, supporting predictive coding models of cognitive function. Additionally, we reveal that early visual cortex contains pattern representations specific to the illusory state, irrespective of tactile stimulation and under identical feedforward visual input. In Chapter 4 we use the motion-induced blindness illusion to demonstrate that feedback modulates stimulus representations in V1 during illusory disappearance. We recorded fMRI data from subjects viewing a 2D cross array rotating around a central axis, passing over an oriented Gabor patch target (45°/ 135°). We attempted to decode the target orientation from V1 when the target was either visible or invisible to subjects. Target information could be decoded during target visibility but not during motion-induced blindness. This demonstrates that the target representation in V1 is distorted or destroyed when the target is perceptually invisible. This illusion therefore has effects not only at higher cortical levels, as previously shown, but also in early sensory areas. The representation of the stimulus in V1 is related to perceptual awareness. Importantly, Chapter 4 demonstrated that intracortical processing can disturb constant feedforward information and overwrite feedforward representations. We suggest that the distortion observed occurs through feedback from V5 about the cross array in motion, overwriting feedforward orientation information. The flashed face distortion illusion is a relatively newly discovered illusion in which quickly presented faces become monstrously distorted. The neural underpinnings of the illusion remain unclear; however it has been hypothesised to be a face-specific effect. In Chapter 5 we challenged this account by exploiting two hallmarks of face-specific processing - the other-race effect and left visual field superiority. In two experiments, two ethnic groups of subjects viewed faces presented bilaterally in the visual periphery. We varied the race of the faces presented (same or different than subject), the visual field that the faces were presented in, and the duration of successive presentations (250, 500, 750 or 1000ms per face before replacement). We found that perceived distortion was not affected by stimulus race, visual field, or duration of successive presentations (measured by forced choice in experiment 1 and Likert scale in experiment 2). We therefore provide convincing evidence that FFD is not face-specific and instead suggest that it is an object-general effect created by comparisons between successive stimuli. These comparisons are underlined by a fed back higher level model which dictates that objects cannot immediately replace one another in the same retinotopic space without movement. In Chapter 6 we unify these findings. We discuss how our data show fed back effects on perception to produce visual illusion; effects which cannot be explained through purely feedforward activity processing. We deliberate how lateral connections and attention effects may contribute to our results. We describe known neural mechanisms which allow for the integration of feedback and feedforward information. We discuss how this integration allows V1 to represent the content of visual awareness, including during some of the illusions presented in this thesis. We suggest that a unifying theory of brain computation, Predictive Coding, may explain why feedback exerts top-down effects on feedforward processing., Lastly we discuss how our findings, and others that demonstrate feedback and prediction effects, could help develop the study and understanding of schizophrenia, including our understanding of the underlying neurological pathologies.

This thesis was submitted in partial fulfillment of the degree of Doctor in Clinical Psychology at the University of Birmingham. The thesis comprises of two volumes. Volume I is concerned with developing a psychological understanding of the psychological impacts and experiences of individuals’ affected by complex grief. It contains three chapters: a meta-ethnography, an empirical paper and a public dissemination document. The meta-ethnography critically reviews qualitative literature of couple’s experiences of a subsequent pregnancy and parenting following a pregnancy loss through miscarriage, stillbirth and/or neonatal death, and provides a higher-level interpretation of these findings. The empirical paper uses Interpretative Phenomenological Analysis (IPA) to conduct an exploration of the lived experience of family members bereaved by heroin overdose. The findings were explored in relation to their applicability to existing models and theories of bereavement. The public dissemination document provides a brief summary using simple language of the first and second chapters, to be accessible to a wider audience. Volume II consists of four clinical practice reports and a summary of an oral presentation describing clinical work undertaken on clinical placements.

This research explores the links between bipolar disorder and work. It focuses on the factors that impact an individual’s ability to work and explores whether a simple intervention to support all the key stakeholders (employees with bipolar disorder, line managers and occupational health professionals) involved in the process can be effective. This thesis involved three distinct parts. In the first part a qualitative focus group study explored the views and experiences of the employee, line manager and occupational health professional (OH) participants with respect to the management of bipolar disorder and work. Consensus was reached across the three groups on the main challenges to managing work and bipolar disorder and the solutions to overcome these. The three groups were in agreement on the key areas to be addressed in the intervention to meet the needs of each stakeholder group. In the second part, a qualitative questionnaire study explored the employment patterns and the impact of clinical and demographic variables on the employment outcome across a large sample of participants with a diagnosis of bipolar disorder. This study identified that individuals with bipolar disorder can obtain and sustain employment for prolonged periods, with some reporting sickness absence levels that match those without a mood disorder. It also identified the key clinical and demographical variablesbest associated with employment outcome, which included educational attainment, age of onset of contact with psychiatric services and length of longest psychiatric hospital admission. In the third part, informed by the literature review and focus group findings, the intervention 'Working With Bipolar' was developed that aimed to improve the interactions and conversations between the three key stakeholders in regard to the management of bipolar disorder and work. This intervention was well regarded among the target users and allowed positive and constructive ideas for change.

Schizophrenia is highly heritable, indicating that a large proportion of one’s susceptibility to developing the disorder is attributable to genetics. Recent large-scale genomic studies have revealed that genetic variants in patients with schizophrenia affect genes involved in synaptic plasticity processes, which are required for learning and memory, including genes encoding protein complexes associated with the NMDA receptor and the postsynaptic density. Further evidence suggests that associative learning may be particularly affected, although it is unclear which components of this cognitive process are implicated in schizophrenia. The present studies investigated the relationship between particular phases of associative learning, represented by the consolidation, retrieval and extinction of contextual fear memory in rats, with genetic variants, psychoactive drugs and postsynaptic density proteins associated with schizophrenia. I tested associative learning-related gene expression datasets for enrichment in genetic copy number variants from a large cohort of patients with schizophrenia and demonstrated that only genes associated with extinction learning are enriched in patient variants (Chapter 3). I report that fear extinction in rats was impaired by administration of the NMDA antagonist and psychotomimetic, ketamine (Chapter 4). The expression of activity- induced, postsynaptic density products of the Homer1 gene, which has been linked to psychiatric disease, was differentially regulated in specific hippocampal subregions following extinction learning (Chapter 5), and the effect of a partial knockdown of these genes during different phases of associative learning was investigated (Chapter 6). These results build on clinical studies linking abnormalities in associative and, specifically, extinction learning with schizophrenia and support the notion that genetic variants associated with the disorder impact particular cognitive domains. My findings are consistent with the theory that altered inhibitory-type learning processes contribute to the manifestation of schizophrenia.

Background: Delusions are common in psychosis, defined as fixed, false beliefs. Some studies, however, have found that they may be less fixed than previously thought, possibly changing in response to talking about them. Relatives of people with psychosis or clinical staff often ask how to respond to them when they talk about their delusions, but no available advice appears to be evidence based. Aims: To review evidence on everyday communication about delusions and find out how people with delusions talk about them with others, taking three perspectives (patients, their nominated relatives and clinicians) and to construct a model for communication in relation to the delusion according to each party independently. Methods: 36 patients were engaged in semi-structured interviews about their mental state generally (Comprehensive Psychopathological Rating Scale) and their delusion (Maudsley Assessment of Delusions Schedule). Each patient was asked to nominate a relative and a professional to whom s/he spoke about the delusion. Relatives and staff were interviewed by different researchers. Results: Most patients reported speaking to others about their delusion and nominated an informant. Most felt emotionally disturbed by their delusions, but, against prediction, this did not affect nomination; nor did their delusion content. There was good agreement between the three parties on occurrence of such communication. Some patients had self-harmed; only some relatives or staff concurred with them on attributing this to the delusion. A testable hypothesis was generated that the intrusiveness of delusions resulted in personal change for the patient and sense of changed relationship and detachment for the others. Conclusions: No previous study has investigated communication about delusions between three parties. It was striking that so few relatives were engaged. If patients, their families and clinicians could improve mutual understanding of delusions, the safety of the patient and others as well as treatment might be improved.

This thesis combines two research papers. The first paper is a systematic literature review investigating risk factors associated with suicidality in Huntington’s disease. The review discusses the importance of clinicians using the identified factors as ‘red flags’ when screening for suicide ideation so that either preventative measures can be put in place or psychological interventions provided to ameliorate any distress. The second paper is an empirical study which explores the concept of ‘rational suicide’ in Multiple Sclerosis (MS). It also investigates whether depression forms an important link between disability and suicide ideation, compares types of Progressive MS and examines whether there are differences in levels of suicide ideation for different disability types. The findings are discussed in terms of current literature, future research recommendations and clinical implications.

22q11.2 Deletion Syndrome (22q11.2DS) is one of the strongest known risk factors for schizophrenia. The syndrome provides a rare opportunity to prospectively examine development that precedes schizophrenia. 22q11.2DS is also associated with a range of psychiatric disorders and cognitive deficits. The overall aim of this thesis is to examine the neuropsychiatric phenotype of 22q11.2DS through a developmental lens. This thesis uses data from Cardiff University’s ECHO (Experiences of CHildren with cOpy number variants) study which includes a longitudinal cohort of children with 22q11.2DS. Development in 22q11.2DS is contrasted to that of the unaffected siblings of children with 22q11.2DS. First psychopathology is examined longitudinally across early adolescence in 22q11.2DS. Children with 22q11.2DS have a significant burden of psychopathology across early adolescence, including attention-deficit/hyperactivity disorder (ADHD), anxiety disorders and autism spectrum disorder (ASD). There is a striking increase in the prevalence of psychotic experiences and a decrease in ADHD prevalence. The ASD phenotype is examined further using a diagnostic interview of developmental history. ASD and subthreshold phenomenology is found to be highly prevalent in the early development of children with 22q11.2DS. Next cognitive development in 22q11.2DS is considered and contrasted to that in unaffected siblings. Cognitive deficits across a range of domains are present in 22q11.2DS. Cognitive development in 22q11.2DS is found to be similar to that reported in children who later develop idiopathic schizophrenia. This is followed by an exploration of the relations between psychopathology and cognitive development in 22q11.2DS. Cognitive development is found to predict the emergence of psychotic experiences and the persistence of ADHD in 22q11.2DS. This thesis extends what is known about the development of the neuropsychiatric phenotype in 22q11.2DS. Furthermore, findings give an insight into the developmental pathways associated with a high risk of developing schizophrenia.

The common mental disorders of anxiety and depression (CMD) impose a substantial burden on individuals and society. A current limitation for research into risk factors for CMD is that the Mental Health Inventory -5 MHI-5) a brief but widely used scale to measure of anxiety and depression was designed without a cut-point to identify cases of CMD. This thesis designed a web-based epidemiological study. Changes in Well-being to gather data from MHI-5 and the Clinical Interview Schedule – Revised (CIS-R), representing the ‘gold standard’ for CMD case classification. From a random sample of 10,000 people aged 18 to 74 years living in Caerphilly County Borough, Wales a total of 616 participants were recruited. Of these, 82 (13.4%) were classified as CMD ‘non-severe’ (CMD-NS) using a CIS-R score of 12-17 and 129 (20.9%) were classified as a case of CMD ‘severe’ (CMD-S) with a CIS-R score of 18 and over. In an analysis of paired CIS-R and MHI-5 scores, the corresponding cut-points on the MHI-5 scaled of 0-100 were <60 and <45 respectively. These cut-points were applied to baseline and follow-up survey MHI-5 scores in the Caerphilly Health and Social Needs Longitudinal Study dataset to classify cases. Logistic regression analysis showed the importance of younger age, a range of major adverse life events, and living in the most deprived areas as risk factors for the onset of CMD. Adverse employment transitions, moving to non-owner-occupation and becoming widowed were more strongly associated with older age groups and living in areas of high social cohesion. This thesis has shown the utility of web-based epidemiological studies in population mental health, determined cut-points on the MHI5 scale and demonstrated the importance of a wide-range of risk factors for change in CMD case status.

Since its discovery over a decade ago, DISC1 has become one of the most promising candidate genes for Schizophrenia and associated chronic mental disorders. This notion has been supported by a wealth of evidence from genetic and biochemical studies. With multiple interacting partners, DISC1 acts as a scaffold protein, orchestrating vital signalling pathways that underpin neurodevelopment and signalling. While the aetiology of Schizophrenia is poorly understood, loss of DISC1 protein function remains one of the proposed disease mechanisms. Furthermore, its tendency to form aggregates is reminiscent of neurodegenerative illnesses such as Alzheimer’s and Parkinson’s disease. C-terminal truncation of DISC1 (TrDISC1) is known to decrease neurite outgrowth and number in the PC12 cell line, abolish protein interaction with proteins such as Ndel1 and also disrupt vital physiological process such as mitochondrial transport. However, very little is known about the underlying disease mechanism at the molecular level. In order to gain insight in to the role of DISC1 pathway in Schizophrenia and associated mental illnesses, I studied novel post translational modifications of DISC1. The main conclusion of my thesis is that these modifications affect DISC1 turnover and its scaffold function. The work described in this thesis has uncovered 2 novel post translational modifications and identified the E3 ligase involved in regulating DISC1 turn over. My work has also laid the foundation for the design and discovery of both peptide and non-peptide, small molecule inhibitors of the DISC1 and its cognate E3 ligase interaction. These inhibitors can serve as both pharmacological tools and for further investigation of the role of this novel interaction in DISC1 pathway and the vital physiological functions it is involved in. Furthermore, this work also indicates the feasibility of controlled and directed differentiation of patient specific iPS cells in to neurons, which act as a useful tool for disease modelling.

Background: There are multiple conflicting theories of depression and clients are frequently given contradictory explanations of their difficulties. Evidence that brings together biological, psychological and social factors of depression would be particularly useful in addressing this. The current study investigates the neural correlates of self-referential processing following psychological intervention for depression. This provides neurological evidence of how a central feature of psychological models may change following therapy. Methodology: Fourteen participants, who had received psychological intervention for depression, underwent functional magnetic resonance imaging scans whilst completing three types of cognitive task: a self-referential processing task, an other-referential processing task, and a graphical task. Participants’ neural activation during self-referential processing was compared to that of ten depressed participants and twelve control participants, which had been collected for a previous study. Results: When positive and negative self-referential processing were considered together, there was no normalisation of neural activation in the post-therapy group, despite normalisation on the BDI II. When positive and negative self-referential processing were considered separately there were fewer areas of significant neural activation during negative self-referential processing in the post-therapy group than in the depressed group. Indicating that neural activation in the post-therapy group normalised. In contrast, during positive self-referential processing, a lack of difference between the control group and the depressed group precluded the possibility of normalisation. Conclusions: The findings provide further support for the importance of the self in models of depression. In presenting neurological evidence in relation to psychological models and psychological therapy, they help bring together biological and psycho-social models of depression. It is possible that the ongoing patterns of atypical activation during self-referential processing represent a vulnerability to future episodes of depression. Possible explanations for the valence-specific findings are discussed and these are highlighted as interesting future research questions. Limitations of the research methodology are discussed and possible directions for future research are outlined.

interventions are recommended for people with bipolar disorder to enable them to effectively self-manage their health, prevent relapse and improve their long-term outcomes. Psychoeducation comprises expert information (on topics such as monitoring mood, lifestyle and medication) and is commonly presented by health care professionals in structured individual or group face-to-face sessions. This thesis reviewed the evidence from randomised controlled trials and qualitative studies that psychoeducational approaches in different formats may or may not be beneficial for patients with bipolar disorder, and consequently found the evidence base to be sparse, particularly with regard to the benefits and drawbacks of different formats of delivery. This thesis explores the feasibility, acceptability and impact of a group-based psychoeducation programme for people with bipolar disorder in Wales (Bipolar Education Programme – Cymru) and a novel internet-based psychoeducation programme (Beating Bipolar) for participants of a randomised controlled trial. Adopting a pragmatic approach, and using both qualitative and quantitative research methods in a predominantly qualitative study, I explored and compared both interventions from the perspectives of patients and facilitators, using qualitative interviews, data from the Beating Bipolar online discussion forum and quantitative outcome data from questionnaires. Findings principally describe the facilitators and barriers to delivery in different formats, what participants liked and disliked about the programmes, the potential impact of the programmes and recommendations for future use, and identify the potential therapeutic mechanisms of psychoeducation. Receiving social support from the groups and enhanced knowledge and understanding of bipolar disorder from the educational content and shared experiences were found to improve many participants’ self-reported confidence in their ability to manage their bipolar disorder, and many made beneficial changes to their lifestyles, coping strategies and their attitudes towards medication and bipolar disorder in general as a result. Future research should focus on widening access to both interventions.

Individuals with schizophrenia have severe cognitive impairments that impact upon their ability to function within society. Better understanding the genetic mechanisms underlying schizophrenia and cognition provides an opportunity for targeted pharmacological intervention. This thesis investigates common and rare genetic variation in schizophrenia and their associations with cognitive ability in schizophrenia cases and healthy controls. Polygenic risk of schizophrenia and bipolar disorder predicted ability on tests of cognitive domains affected in schizophrenia, performance, verbal and full scale IQ in healthy controls. Increased polygenic risk of schizophrenia was robustly associated with lower performance IQ at different training thresholds in two independent cognition samples. There was no consistent association between bipolar polygenic risk and cognition. Common genetic differences between schizophrenia and bipolar disorder were associated with verbal and full scale IQ. I investigated the hypothesis that 155 gene-sets across six biological categories relating to cognition, brain function and structure were enriched for SNPs influencing general cognitive ability. Schizophrenia polygenic pathway scores for gene-sets were not associated with general cognitive ability in schizophrenia patients, or performance IQ in healthy individuals. Separately, neither gene-sets vi nor general categories were enriched for common SNPs showing association with general cognitive ability in schizophrenia cases. Associations between rare CNVs and general cognitive ability were tested in schizophrenia cases. Cases with a known pathogenic CNV performed approximately one standard deviation below other schizophrenia cases on the MATRICS composite score. In addition, increases in the number of genes hit by large (>100kb) and rare (frequency <1%) CNVs were associated with lower general cognitive ability. However, the number of genes hit in gene-sets previously mentioned was not associated with the MATRICS composite score. These findings indicate genetic variation in schizophrenia is associated with cognitive ability in schizophrenia cases and healthy controls, providing direction for future research.

Background: Theories of motivational conflict are key in understanding alcohol misuse. Research suggests that approach and avoidance motivation are two distinct systems and that level of alcohol consumption depends on which system is most activated at one time. One factor thought to influence this balance is the role of implicit processes. This study aimed to investigate the effects of implicitly priming one motivational system (i.e. approach / avoidance) on the opposing system in regard to alcohol-related motivation in heavy drinkers. Methods: Heavy drinkers were recruited from a non-clinical community sample to complete a protocol of stimulus response compatibility and visual probe tasks designed to measure implicit motivation by recording reaction times to alcohol cues. Participants were assigned to one of three groups and attempts were made to manipulate implicit motivation using a masked priming paradigm. Measures of explicit attitudes towards alcohol were also administered. Results: No significant effects of priming were found. The overall sample showed attentional avoidance for alcohol cues presented at 50 ms duration but not at 500 ms. On the SRC task, participants were slower to avoid alcohol cues than neutral cues. Positive correlations were found between attentional bias for alcohol cues presented for 500 ms on the visual probe task and craving and consumption as measured by the Alcohol Approach Avoidance Questionnaire (AAAQ) and the Alcohol Use Disorders Identification Test (AUDIT) respectively. Significance: Implicit priming of alcohol-related motivational states had no influence on indices of alcohol approach and avoidance motivation or on attentional bias. As an overall sample, heavy drinkers showed automatic attentional avoidance of alcohol cues presented at short durations (50 ms). This is the first study to find avoidance of alcohol cues presented at this duration in heavy drinkers.

Traumatic brain injury (TBI) belongs to a classification of injury called Acquired Brain Injury (ABI). ABIs are brain injuries that have occurred since birth with possible causes including stroke, haemorrhage and infection (Powell, 2004). TBIs are a result of insults to the brain from external forces. TBI can lead to altered states of consciousness along with impairment of cognitive, physical, and psychosocial functions (Dawodu, 2011). The current research base has often recruited people with a variety of ABIs . This has been a criticism of the literature as ABIs do not affect individuals in the same way, with survivors presenting with a wide range of impairments which family members must adapt to (Newby & Groom, 2010) . This thesis will focus on TBI as a distinct sub-group. Literature referring to TBI will primarily be used. The empirical study will recruit family members of those specifically with a TBI. The narrative review will review papers primarily derived from TBI literature alongside those that explicitly refer to TBI. Both ABI and TBI have significant psychological consequences for the individual and the wider family system (Panting & Merry, 1972; Lezak, 1986; Carnes & Quinn, 2005; Holm, Schönberger, Poulsen, Caetano, 2009 ; Braine, 2011). Research focused on the family in ABI/TBI has advanced in recent years , yet there is still much to learn about family functioning post injury, and equally how research can advance understanding of the best interventions to aid family members (Oddy & Herbert, 2008). This thesis will be divided into three sections and each will have a specific focus. The overarching theme will be considering how research and practice in TBI can be understood as a social phenomenon. Bowen, Yeates and Palmer (2010, p. 304) discuss that there is a need to see “ brain - 2 - injury as existing within the spaces between people. A focus on systemic thinking in conceptualising brain injury will first be applied to a narrative review. Section 2: Adult Traumatic Brain Injury (TBI): A narrative review of family therapy as a conceptual model in research with family members. The review addressed two research questions: • What are the essential attributes of the model of family therapy when applied to TBI? • How could this model be applied as a conceptual framework in TBI research? The findings will propose that, family therapy could provide a conceptual framework to guide research and give it greater coherence. A guiding conceptual framework is presented which is then discussed in relation to its implications for research and practice. Section 3: Sense-making through observation and action: A grounded theory study investigating how family members of traumatic brain injury (TBI) patients construct an understanding of injury. The study aimed to address some of the considerations for future research in the narrative review, primarily that there is a greater need “ to have an appreciation of the family as more than a collection of individuals living together in the same physical or psychological place” (Leaf, 1993 , p.3-543). Additionally, that current theory is stronger in terms of understanding the consequences of brain injury but relatively lacking in terms of understanding the family’s response (Perlesz, Kinsella & Crowe, 1999). The rationale for the study is outlined before the methodology is delineated. An epistemological position of constructivism was used to try and investigate a number of aims centring on how family members make sense of TBI. The paper will present a model of sense-making that developed from a grounded theory design as set out by Strauss and Corbin (1998). The empirical paper will discuss the findings in terms of their implications for practice and research alongside strengths and limitations of the study.

Goal pursuit is a central element to the developmental stage of adolescence. However, little is known about how adolescents within the Youth Justice System think about their personal future. This present study explores how 14 adolescents in a Youth Offending Service think about their goal aspirations and personal future. Grounded Theory was used to focus upon individual and situational factors that contributed to the process. A theoretical framework was developed which outlined that engaging in thinking about one’s personal future and developing goal aspirations is influenced by appraisal of past and present life events. Central to the development of the theoretical framework was the recognition that participants employed a range of self protecting strategies to avoid against uncertainty and threat of future disappointment. Findings of the study are discussed and clinical implications, methodological considerations and possible areas for further research are presented.

This thesis examines Body Dysmorphic Disorder (BDD) and body dysmorphic concerns in a clinical and non-clinical sample. The opening section of the thesis provides an outline of the clinical features, prevalence, onset and course of BDD and related concerns. This is followed by a literature review and examination of two related areas of research: (a) the evidence base for cognitive-behavioural psychological interventions for the treatment of BDD, and (b) studies investigating the potential role of internal and external perfectionism, shame and self-discrepancies in relation to the experience of BDD. The remainder of the thesis reports two empirical studies of aspects of BDD and dysmorphic concerns. Study 1 (n=4) reports a clinical evaluation of a cognitive-behavioural group therapy treatment of the disorder, employing both single-case experimental design methodology and analysis of average change pre- to post-therapy and at 6-month follow-up. Data indicated that BDD symptoms along with some problems such as depression and self-esteem responded favourably to treatment while problems like shame did not. Appearance-related and interaction-based social anxiety responded to treatment in two out of four clients. Study 2 (n=547) reports an investigation of the role of internal and external perfectionism, shame and self-discrepancies in relation to BDD. This employed an online survey methodology with a student sample, entailing completion of a number of self-report psychometric assessments. Results showed that external shame was the variable most strongly associated with body dysmorphic concern. Combined with discrepancies between actual and ideal self-concept, these two variables accounted for the greatest proportion of variance observed in dysmorphic concern scores. Outcomes are discussed in terms of the strengths and limitations of the study methodologies, existing literature on CBT and predictors of dysmorphic concern, and the possible need to include additional variables in the treatment of BDD.

Introduction Individual cognitive behaviour therapy for psychosis (CBTp) is a recommended treatment in the acute phase and beyond. However, less is known about the effectiveness of group CBTp in acute care. This mixed methods study explored the implementation and effectiveness of brief group CBTp with inpatients. Methods This prospective trial compared inpatients who received either a four week group CBTp program or treatment as usual (TAU). Participants (n=113 at baseline) completed self-report measures of distress, confidence and symptoms of psychosis at baseline, post-intervention and one month follow up. CBTp group participants also completed a brief open-ended satisfaction questionnaire. Results Participants who received CBTp showed significantly reduced distress at follow up compared to TAU and significantly increased confidence across the study and follow up period. Qualitative analysis of the satisfaction data revealed positive feedback with a number of specific themes. Conclusion The study demonstrates that brief group CBTp with inpatients can improve confidence and reduce distress in the longer term. Participants report that the groups are acceptable and helpful.

Theory and research in the field of persecutory beliefs have identified a number of important psychological processes involved in clinical and non-clinical paranoia. This dissertation set out to investigate some of these processes. Firstly, the empirical evidence for the distinction of 'Poor Me' and 'Bad Me' paranoia (Trower & Chadwick, 1995) was reviewed systematically. Secondly, an empirical study with two phases aimed to investigate the contribution of key processes to paranoia in clinical and non-clinical samples. Investigated factors were: anxiety, depression, anger, attachment anxiety, attachment avoidance, deservedness, submissiveness, self-attacking, self-compassion and experiential avoidance. The review found the distinction of 'Poor Me' and 'Bad Me' paranoia to have some validity and clinical usefulness; however, as yet not all of the theoretical predictions have been borne out in the empirical literature. The importance of the role of deservedness and its measurement was discussed. A series of one-way ANCOVAs found levels of a number of processes to distinguish clinical and non-clinical paranoid groups. Hierarchical regression revealed experiential avoidance to be a significant predictor of paranoia in the final model. A concluding section synthesised these findings and consideration was given to future directions.

Measuring the quality of life (QOL) of individuals who live with long-term health conditions and illnesses has become more important in the absence of cure (Department of Health [DoH], 2013). Dementia is an intractable, progressive and terminal illness and recent research from the Alzheimer’s Society (2012) has highlighted that a large proportion of those with dementia report that they do not live well with dementia and indicates the impact of this on QOL. Historically, there was an assumption that individuals living with dementia, due to their cognitive impairment, were unable to comment and talk about their QOL, however more recent research has shown that this is not the case (Woods, 2012). There are a number of ways in which QOL can be explored. For example, a number of scales have been developed which can collect information through a variety of methods including: self-report (e.g., Dementia Quality Of Life: Brod, Stewart, Sands, & Walton, 1999), report by-proxy (e.g., Alzheimer’s Disease Health-Related Quality Of Life: Rabins, Kasper, Kleinman, Black, & Patrick, 1999), observational (e.g., Dementia Care Mapping: Kitwood & Bredin, 1992) or through a combination of such methods. Quality of life is highly subjective and this poses challenges for the collection of information about QOL. Numerous studies have highlighted the discrepancy between self-report and proxy report QOL scores (for a review see Ettema et al., 2005), and difficulties with observational methods such as observer bias are evident. Such observations suggest that self-report, where possible, is the gold standard for the measurement of QOL (Cahill & Diaz Ponce, 2011), although this is also not without difficulty (Ettema et al., 2005). Self-report scales of QOL for those living with dementia certainly have their utility; however, the application of such scales for those with advanced dementia seems variable. This may partly be due to the loss of verbal communication and understanding (Johnson et al., 2009). This is further explored as the main focus of the narrative review which discusses and critiques the body of research which has been published in the last ten years which has focused on the self-report of QOL. The studies reported in the review; three quantitative articles and three qualitative articles discuss different methods for the collection of information regarding QOL from those individuals living with dementia. Findings from the review suggest that whilst self-report scales for QOL can be highly useful and effective, it seems their most effective use is with individuals who have mild to moderate dementia (Karim, Ramanna, Petit, Doward, & Burns, 2008; Trigg, Jones, & Skevington, 2007a; Trigg, Skevington, & Jones, 2007b). Some studies included in the review reported the inclusion of participants with advanced dementia. However, it would seem that participants with advanced dementia are more likely to struggle answering some questions, leading to missing values: a similar observation was reported by Ettema et al. (2005). The review highlights, therefore, the growing need for accurate self-report measurement of QOL for those with advanced dementia. The qualitative studies reviewed indicated that interviews employing semi-structured or unstructured frameworks could be successful in gaining meaningful information from those living with advanced dementia about their QOL (Clare, Rowlands, Bruce, Surr, & Downs, 2008; Cahill & Diaz-Ponce, 2011). It seemed as though there were numerous advantages from using a qualitative method for collecting information from those living with dementia, and therefore this was the methodology adopted in the study. The empirical study invited participants to think about their QOL in the context of their diagnosis of dementia and to also consider their expected future QOL in light of advancing dementia. Given some of the challenges of communication from those with advanced dementia, the study recruited those with mild to moderate dementia to think about the future. Thinking about the future of dementia was anticipated to be highly emotive and potentially very distressing for participants, therefore through the use of one-to-one interviews, participants could be asked difficult and challenging questions sensitively. Participants described factors which impacted on their QOL such as reciprocal relationships, impact of skill loss and being supported by relatives. However, thinking about the future seemed more challenging for the participants. Some participants did express fear and uncertainty when asked to think about the future, and this was something that the majority of participants did not want to do. However, some participants expressed difficulties which their spouse or partner had when it came to considering the future and the terminal nature of the dementia. For some participants, having such conversations may be important and not doing so could be detrimental to QOL. This was discussed in the professional report for healthcare professionals, amongst other recommendations and clinical implications from the findings of the current study. Perhaps some of the fear and uncertainty generated by thinking about the future in terms of dementia, which the participants expressed, was related to stigma and misperceptions about dementia. There is little research on the impact of stigma for those living with dementia (Mukadam & Livingston, 2012), most of the research is focused on psychosis (schizophrenia) and therefore, exploring stigma in the context of dementia was considered as a direction for future research. In the Dementia Strategy, the DoH (2009) drew attention to stigma and the social awareness of dementia; this has remained a matter of interest for the current government, reflected in multimedia advertising and other campaigns. Future research based on the findings of the current study, might focus upon ways in which stigma and the misperceptions about dementia could be further explored.

Reader groups involve the reading aloud of complex literature by a skilled facilitator in a group setting, followed by group discussion in relation to the text. They are delivered to a wide variety of populations within both physical and mental health and social care services, across community, residential and inpatient settings. A limited body of existing literature indicates that reader groups can produce positive therapeutic effects to enhance mental health and well-being, but research thus far is largely based on pilot studies with small samples. Further investigation is warranted to explore the experience of reader groups from the perspective of individuals with mental health problems and to consider possible psychological mechanisms underpinning potential therapeutic effects, since this is the first psychological study to be conducted in this area. The aim of the current research was to explore the experience of being in a community reader group for people with mental health problems, and to consider how participation relates to making sense of life experiences and relationships, both inside and outside the group. Eight participants took part in semi-structured interviews, which were transcribed and analysed using Interpretative Phenomenological Analysis. Five master themes pertaining to participants’ experience of reader groups emerged: ‘Literature as an Intermediary Object’, ‘Boundaries and Rules of Engagement’, ‘Self as Valued, Worthy, Capable’, ‘Community and Togetherness in Relational Space’, and ‘Changing View of Self, World, Others’. The findings were discussed in relation to existing literature, to provide an indication of possible psychological mechanisms underpinning participants’ experiences of reader groups. Clinical implications of the current research were considered, particularly in terms of mental health service provision and access to alternative therapeutic activity, and suggestions were made for future research.

This thesis is submitted in partial fulfilment of a Doctorate in Clinical Psychology at the University of Liverpool. It focuses on the frequently reported finding of reduced specificity of autobiographical memory in participants diagnosed with depression (Williams & Broadbent; 1986, van Vreeswijk & de Wilde; 2004). That is, difficulty recalling the who, what, where and when, of a remembered event. The focus of investigation particularly within the thesis is that of executive functioning; a term describing a range of higher order cognitive functions that control and integrate other activities such as planning, sequencing, initiation. It is examined in relation to depression. The thesis is presented in paper form; Chapter 1 contains a systematic review of 9 research studies related to executive function in the memory specificity of participants with a diagnosis of depression. While executive functioning does appear to be related to reduced specificity the findings in the literature are not consistent highlighting the need for further research. The original empirical paper presented in Chapter 2 tests out hypotheses related to the claims of reduced specificity and executive functioning in participants with a diagnosis of depression (Burt, Zembar, & Niederehe, 1995). These hypotheses are based on the conclusions drawn from the review paper in Chapter 1. It concludes that while overall participants with a diagnosis of depression produce fewer memories overall, and particularly fewer specific memories, this difference can be reduced with modified materials which are more concrete and imaginable. These modified materials can also produce more specific memories overall. In addition, regardless of depression status, executive functioning has a significant impact on autobiographical memory specificity. These key findings are developed in an extended discussion in Chapter 3 and discussed in terms of their value and application to practices in clinical psychology. Chapter 3 also contains research dissemination for participants and a future research proposal expanding the scope of investigation from depression to trauma.

Post-traumatic growth (PTG) is the experience of positive changes as a result of a traumatic event, where well-being and personal functioning exceed that of pre-trauma levels (Tedeschi, Park, & Calhoun, 1998). The occurrence of PTG following a variety of traumas has been examined, and a number of meta-analyses and reviews have attempted to summarise such literature and determine what facilitates PTG (e.g. Linley & Joseph, 2004). Some of these seek to establish whether there are differences in the experience of PTG dependent on the cause of the trauma (e.g. Bostock, Sheikh, & Barton, 2009). It has been suggested that the character of PTG following a serious accident may be different to that following physical illness, for example, with physical illness being experienced as an internal trauma and an accident as an external trauma (Hefferon, Grealy, & Mutrie, 2009). There are no reviews which explore the literature around PTG following a serious accident. Paper one of this thesis is a systematic review of the quantitative literature which aims to investigate the experience of PTG following serious accidents. A burn injury can be a traumatic event and can be challenging to recover from, both physically and psychologically (Blakeney, Rosenberg, Rosenberg, & Faber, 2008). Although the psychological impact of burn injuries is undisputed (Wisely, Hoyle, Tarrier, & Edwards, 2007), little attention has been paid to the benefits of such traumas (Fauerbach, Pruzinsky, & Saxe, 2007). Several qualitative studies exploring individuals’ experiences of a burn injury refer to positive changes which can accompany distress and trauma; however, only one quantitative study has directly explored the concept of PTG post-burn (Rosenbach & Renneberg, 2008). Paper two of this thesis is an empirical paper which aims to build on this, using quantitative methods to explore the concept of PTG following a burn injury.

This thesis broadly explores evidence-based practice (EBP) in mental health, with a particular focus on dissemination and implementation of research evidence regarding family intervention in psychosis. Chapter one comprises a review of evidence-based practice in mental health, including the uptake of evidence-based practice, the effects of training, research dissemination and implementation strategies. A brief narrative review is presented followed by a systematic review examining uptake of evidence-based therapies by mental health practitioners. Eleven papers were selected for review and were measured against the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines (von Elm, Altman, Egger, Pocock, Gøtzsche & Vandenbroucke, 2007). Following this, conclusions regarding the current evidence and areas which need to be developed are discussed, primarily the need for standardised measures, an indication of clinical change and provision of follow-up studies. Chapter Two comprises an empirical paper intended to be submitted to the journal ‘Implementation Science’. The aim was to address some of the issues identified in Chapter One, namely the use of standardised measures and the measure of a change in clinical practice. Mixed methods were used to assess attitudes to EBP in Trainee Clinical Psychologists and the effect that different dissemination methods had on their attitudes to a specific facet of EBP, family interventions in psychosis. A total of 104 trainee clinical psychologists from 23 UK training programmes participated in the online study, and were randomly allocated to one of four conditions. i. ‘Minimal information’: Participants viewed a brief summary of a fictitious service-user with psychosis, this served as the baseline condition. ii. ‘Case study’: Participants viewed a detailed case study describing the use of family interventions with a fictitious service-user with psychosis iii. ‘Research summary’: Participants viewed a detailed research summary showing research into the effectiveness of family interventions in psychosis iv. ‘Combined’, participants viewed both the case study and research summary Following this, participants completed a survey of their experience with different therapies and demographic information and a standardised measure of attitudes to EBP. Participants then viewed the minimal information about the fictitious client, followed by the summary specified in the condition they were allocated to. Participants then completed a questionnaire designed to assess their attitudes to family intervention in psychosis and their willingness to engage in further training. Responses to these served as the dependent variables. Participants were also given the opportunity to give their own views on the use of family interventions in clinical practice. Data were analysed using MANOVA and multiple regression, with thematic analysis (Braun & Clarke, 2006) employed for the qualitative data. Participants who viewed both case and research information showed a greater willingness to train than those who viewed research information alone. Chapter Three, the concluding section, consists of a general discussion of the research, focusing on the findings and their relation to previous findings in the area, the implications of the findings for research and clinical training and practice, as well as strengths and limitations of the research. The main limitations identified were the lack of a follow-up and the suitability of willingness to train as a measure in trainee clinical psychologists. Recommendations for future research in this area are made. Following the general discussion section a proposal for a follow-on study, extending the current study and improving the methodology is presented. Lastly, the research is presented in the form of a report intended for submission to ‘Clinical Psychology Forum’.

Disease loci underlying complex disorders such as schizophrenia(SCZ)are likely to exist as variants of multiple typesbeyond the single nucleotide polymorphisms(SNPs) typically surveyed in genome-­‐wide association studies(GWAS). Large copy number variants (CNV), small insertions and deletions (INDELS),rare compound heterozygous mutations and other classes of genetic variation are all expected to contribute to disease risk. A true understanding of disease genetics cannot be attained without careful consideration of each class of variation and how they are related. Additionally, it is often the case that no or few single variants have strong enough effect sizes to attain the level of statistical significance required to offset the large number of tests performed in a genome-­‐wide single locus survey of any variant type. It has been shown that a cumulative burden of risk alleles is correlated with disease risk, indicating true biological signal within those variants. However, this approach merely implicates that class of variation across the genome and does not refine variants to a subset of risk regions or genes. Defining sets of genes within biological pathways and testing them as a group will allow for both the power of aggregating loci of small effect and interpretation of the underlying biology. This dissertation assesses the role of multiple classes of variation from different technologies in risk to schizophrenia with a particular focus on brain related biological pathways.

Schizophrenia is a highly heritable, common psychiatric disorder. Although onset generally occurs during adolescence, multiple lines of evidence point to a neurodevelopmental insult that occurs many years prior to the presentation of symptoms. Many different approaches have been used to elucidate the genetic risk factors and their impact; however, few unequivocal facts have been established. With a considerable amount of data publically available, integrative approaches look to leverage multiple data sources to identify coherent themes. This thesis investigates the neurodevelopmental hypothesis of schizophrenia by incorporating results from genome-wide association studies and copy number variation studies with gene expression datasets, with the overall aim of identifying functional pathways that may be disrupted in the aetiology of the disorder. This study used foetal and developmental expression datasets of the human brain and statistical approaches to characterise the expression profiles of schizophrenia risk genes. Both spatial profiles in the mid-foetal brain and temporal profiles across development were considered. Data from genome-wide association studies and copy number variation studies were used to test for an enrichment of risk genes; in addition the genetic overlap with bipolar disorder identified through genome-wide association studies was used for validation. Gene sets with a common expression profile enriched for schizophrenia variants were used to identify biological pathways and assessed for their polygenic contribution to schizophrenia risk. The results of this thesis converged on a common developmental expression profile for schizophrenia risk genes. Genes identified with this profile were shown to harbour multiple, common risk variants for schizophrenia and were implicated in epigenetic processes relating to the regulation of gene transcription. Together this suggests that schizophrenia associated genes are involved in brain development, particularly during foetal stages, and may play a role in the regulation of this process.

Schizophrenia is a debilitating psychiatric disorder with high heritability. Genome wide association studies (GWASs) have identified association between schizophrenia and an intronic single nucleotide polymorphism (SNP) in zinc finger domain containing 804A (ZNF804A). The biological functions of ZNF804A are largely unknown. Thus, the aim of this thesis was to determine the function of ZNF804A. Yeast two-hybrid (Y2H) screens were used to determine the protein binding partners of ZNF804A in the brain. This identified ZNF804A interacted with transcription factors (zinc finger protein 40 (ZNF40); trans-acting transcription factor 1 (Sp1) and basic helix-loop-helix family, member e40 (Bhlhe40)) and regulators of pre-mRNA splicing, including RNA binding protein, fox-1 and -2 (Rbfox1 and RBFOX2) and neuro-oncological ventral antigen 2 (NOVA2). Therefore, we hypothesised that, via interactions with its protein binding partners, ZNF804A may have a role in regulating transcription and pre-mRNA splicing. Exon arrays were used to determine the effects of ZNF804A knockdown on gene expression in SH-SY5Y neuroblastoma cells. Enrichment analysis on the differentially expressed or spliced genes indicated a significant effect of ZNF804A knockdown on genes involved in nervous system development, particularly synaptic contact and axon guidance. Among the most significantly differentially expressed genes were the known schizophrenia susceptibility genes reelin (RELN) and neuropeptide Y (NPY). Several alternative splicing events were confirmed empirically, including increased exclusion of exon 11a of enabled homolog (ENAH). Consistent with our hypothesis, splicing of exon 11a of ENAH is known to be regulated by RBFOX2. In complementary experiments, exon arrays were used to identify differentially expressed genes in a stable cell line expressing myc-ZNF804A. Enrichment analysis on the differentially expressed genes indicated an over-representation of genes involved in the regulation of epithelial to mesenchymal transition and receptor-mediated axon growth repulsion. Among the genes with the largest fold changes in expression was a gene implicated in synapse development: secreted protein acidic and rich in cysteine (SPARC). Enrichment analysis of the alternatively spliced genes indicated a significant effect of myc-ZNF804A over-expression on genes involved in cell-matrix interactions. These data suggest that ZNF804A regulates the expression of genes implicated in processes underlying schizophrenia pathology, and provide the first evidence that ZNF804A may be involved in the regulation of alternative splicing.

Genome-wide association studies have identified TCF4 (transcription factor 4) as a susceptibility gene for schizophrenia. In addition, rare TCF4 mutations cause Pitt Hopkins syndrome (PTHS), a severe form of intellectual disability associated with characteristic facial features, developmental delay and autonomic dysfunction. TCF4 belongs to the basic helix-loop-helix family (bHLH) of transcription factors that play a central role in development, however the precise function of this gene in the brain is unknown. In this study, I use molecular and cellular techniques to improve our understanding of TCF4 function in the brain. Modeling of PTHS-associated missense mutations in transfected cells showed that TCF4 mutations affecting the DNA-binding domain cause mislocalisation of the mutant protein. DNA-binding domain mutations also impaired dimerisation and attenuated transcriptional activity at the NRXN1 and CNTNAP2 promoters. TCF4 mutations affecting other domains of the protein had context-specific deficits in dimerisation and transactivation under the same conditions. Microarray analysis of SH-SY5Y cells where all TCF4 isoforms had been knocked down identified gene expression changes affecting cellular processes including epithelial-to-mesenchymal transition, apoptosis and neurodevelopment. However, isoform-specific knockdown experiments showed that TCF4-A and TCF4-B isoforms affect distinct biological processes such as the cell cycle, chromatin modification (TCF4-B), cell adhesion and cytoskeletal remodeling (TCF4-A). Finally, mass spectrometry was used to identify TCF4-associated proteins in SHSY5Y cells. These experiments showed that TCF4-B and TCF4-A co-purified with proteins involved in chromatin organization, cell cycle control and RNA splicing. In addition to the bHLH factors HAND2 and TWIST2, TCF4 co-purified with components of the nuclear co-repressor complex. TCF4 also has multiple phosphorylation sites in both activation domains suggesting that TCF4 function may be regulated by kinase signaling. In conclusion, these data provide a mechanistic insight into the function of TCF4 that may advance our understanding of disease processes in PTHS and schizophrenia.

This dissertation for the Doctorate of Clinical Psychology at the University of Liverpool focuses on the experiences of receiving dialectical behaviour therapy (DBT) in the community by adults diagnosed with borderline personality disorder (BPD). It comprises three distinct chapters, namely a literature review, an article detailing an empirical study, and an extended discussion. Chapter one presents the findings from a literature review that systematically searched the qualitative literature for studies that explored the experiences of receiving community-based DBT by adults diagnosed with BPD. The chapter begins by briefly describing the history, diagnostic criteria, prevalence, and symptoms of BPD, before describing the components of DBT, a psychological treatment that has received strong empirical support for the treatment of BPD. Findings from the systematic search of the qualitative literature reveal five articles that fit the review’s inclusion criteria; this paucity of qualitative research investigating clients’ accounts of DBT in actual clinical settings is surprising considering that DBT has received growing support for its efficacy since the publication of its treatment manual in 1993. When considering the findings from the five qualitative articles, the picture of clients’ experiences of DBT is unclear, as the studies vary fundamentally in their research design. For example, the qualitative studies differ in their research design, including the use of structured interviews, semi-structured interviews, and focus groups, and vary in the methodological approaches deployed to analyse the data. Also, the DBT programmes from which participants were recruited in the qualitative studies differ in their fidelity to the DBT model. With the systematic search of the qualitative literature revealing so few studies exploring the experience of receiving community-based DBT by adults diagnosed with BPD, together with their methodological and analytical differences contributing to an unclear account of the experience, chapter two of this dissertation presents an empirical study aiming to augment the qualitative literature that explores the experience of receiving community-based DBT by adults diagnosed with BPD. This empirical study is vital as not only does it consolidate the existing qualitative research, but, remarkably, is believed to be only the second study of its kind to be conducted in the National Health Service (NHS), with the first being conducted over 6 years ago. The aims of the empirical research are to capture participants’ expectations and experiences of the DBT programme, the impact and experience of the multi-modal components of the programme, determine the meaning of a ‘life worth living’ to someone diagnosed with BPD, and gauge whether DBT contributes to a ‘life worth living’, which is DBT’s overarching aim. Six participants are interviewed, all of whom are diagnosed with BPD and have experience of a community-based DBT programme delivered by the NHS. Six themes are found from analysing the qualitative data derived from the interview transcripts. As the intention is to publish both the literature review and empirical paper in academic journals, and academic journals invariably set a limit regarding the maximum number of words or pages for research articles, the third chapter of this dissertation elaborates on the points made in the discussion section of the empirical article in chapter two. The elaborations extend the implications of the findings to the wider research. Links are made to the wider research literature that focuses on group therapies, and the literature suggesting that those diagnosed with BPD struggle to foster therapeutic alliances with therapists. Links are also made to clinical practice, especially in light of fundamental changes to the landscape of the NHS, such as the Coalition Government’s target to make £20 billion of efficiency savings within the NHS by 2014, and the NHS now facing competition from ‘Any Willing Provider’ offering healthcare provisions. Overall, the participants’ experiences of DBT found by the empirical study presented here is encouraging, and it is hoped that such positive views from users of the NHS may go some way to balance the criticism the NHS has received over the years regarding the quality of care it provides to the public. Chapter three also includes a different version of the empirical article, written for employees and clients of the Trust in which the research was conducted. Chapter three concludes with a section detailing how the empirical research presented in this study could be usefully extended.

Dissertation submitted in partial fulfillment of Doctorate in Clinical Psychology. Includes three chapters; a narrative literature review of coping with minority stress in gay men, empirical study exploring the the benefits of self-compassion for well-being in gay men and a expanded discussion chapter.

The aim of this longitudinal, qualitative PhD was to explore the commissioning and implementation of early intervention services for first episode psychosis across a number of sites in England. Methods: After a literature review of policy, implementation, and empirical RCT and cohort studies, 147 semi-structured interviews and six focus groups involving 35 people from different managerial and operational levels of the health service were undertaken between February 2004 and March 2009. May’s Normalization Process Theory was used as the underpinning conceptual framework and data were analysed using the Framework Analytical Approach. Results: the main findings were the importance of partnership working, influenced positively by the role of a facilitator; challenges which arose when commissioning mental health services, alleviated by the involvement of senior managers acting in a mentor role and the ‘work’ undertaken, from the perspective of Normalization Process Theory. A new service model, called the ‘trailblazer’ early intervention service was identified, which is not accounted for within Normalization Process Theory. Conclusion: further work is needed to define the characteristics and qualities of the mentoring role of senior managers and the facilitator and explore how best to adapt and extend Normalization Process Theory to incorporate the new ‘trailblazer’ service model.

The use of cannabis has been found to be prognostic of poorer symptomatic outcome among people with first-episode psychosis. It is therefore important to understand what motivates the use of cannabis in this population. Using a twelve month prospective design this research aimed to quantitatively assess the impact of cannabis use on the symptoms of psychosis, mania, depression and the level of functioning among people with first-episode psychosis. The research also aimed to identify if the motives for cannabis use, such as reasons and expectancy, a person's social network and self-perceived social status may be associated with cannabis use, cessation or abstention. Qualitative methods were also used to explore the factors that the participant perceived to relate to cannabis use and cannabis abstention among people experiencing their first-episode of psychosis. This research found the continued use of cannabis to be associated with increased severity of mania and to impede recovery in psycho-social functioning. The results suggest that similar reasons and expectancies motivate the use of cannabis in young people with and without psychosis. Concern regarding the potential adverse effect of cannabis use on mental health was found to be influential for cannabis cessation and abstention; and abstention from cannabis was also associated with greater negative cannabis expectancy. The sample sizes in this research may have meant that a small number of analyses were underpowered to detect significant differences for some variables. Nevertheless, the results of this research highlight the deleterious effect that continued use of cannabis may have for II people experiencing their first-episode of psychosis. Psycho-education regarding the potentially adverse effects of cannabis use may help to enhance current intervention efforts among this population; however intervention must emphasise "normal" motives for cannabis use rather than psychosis specific motives.

Schizophrenia is a complex disorder, with several genes putatively associated with the pathogenesis of the disorder. A large genome-wide association study (O’Donovan et al. 2008) identified ZNF804A as a candidate gene for schizophrenia (meta-analysis p = 1.61 x 10-7). The association of the gene with schizophrenia (and bipolar disorder) has since been successfully replicated several times, confirming the association (Riley et al., 2010; Steinberg et al., 2010; Zhang et al., 2010, Williams et al., 2011). The aim of this thesis is to create and provide preliminary assessments of a mouse model of the murine form of ZNF804A, Zfp804a. A mutagenised DNA archive derived from mice treated with N-ethyl-N-nitrosourea (ENU) held at the MRC Mammalian Genetics Unit, Harwell, was screened for mutations in Zfp804a. Two mutations (C59X and C417Y) were selected for re-derivation based upon the estimated impact upon the protein. The mutations were backcrossed onto a C57Bl/6J background for three successive generations using a panel of genetic markers to aid selection for the highest level of C57Bl/6J congenicity (and therefore speed up the backcrossing process). G4 mice were tested in the study. Preliminary assessments of the fourth generation intercross cohort revealed, most notably, that the mice breed well, have no gross physical deficits and that male Zfp804aC59X/C59X mutants appeared less anxious than other groups in the elevated plus maze and performed better than other groups on the RotaRod. Initial indications show that Zfp804a may indeed influence behaviour and cognition however further work is necessary to expand upon these findings with larger samples.

Bipolar disorder is a severe and enduring mental health condition. Although early identification is associated with better outcomes, research has shown that many people wait over a decade after first experiencing affective symptoms before a correct diagnosis is made. A misdiagnosis of unipolar depression often leads to the inappropriate prescription of potentially mood-destabilising antidepressant medications. The aim of this study was to consider service user and carer experiences and their often overlooked views on diagnostic issues. Participants were recruited via the charity Bipolar UK. Initially a focus group discussed the diagnostic process and relevant issues, then the transcript was analysed thematically and used to develop a detailed survey questionnaire. The survey was piloted before being launched online and completed by 262 service users and 65 carers. Survey respondents reported an average delay of over eleven years between first seeking help for bipolar symptoms and being correctly diagnosed. Almost 70% reported a previous misdiagnosis of depression, and over half had experienced mania/hypomania whilst taking antidepressant medication. Nearly a third consulted a doctor over 20 times with bipolar symptoms before receiving help for bipolar disorder. Participants considered that improvements are needed in primary care mental health assessment and that GPs need more training. Many reported that their condition had led them to be discriminated against and agreed that society’s lack of understanding was a major problem. Carers indicated similar opinions and emphasised the potential benefits of including carers in the assessment process. This study suggests that the identification of bipolar disorder is often poor and that assessment of the condition in primary care needs to be improved. Service users offered suggestions for improvements, including recognition of early indicators, appropriate assessment questions and better training which could be adopted by service providers. Limitations of the study and implications for future research were discussed.

This thesis explores the effects of transcranial magnetic stimulation (TMS) on conscious perception and visual processing. Chapter 1 addresses issues of experimental design. Two broad classes of TMS intervention were used and are reported in separate chapters. Chapter 2 involves repetitive ‘off-line’ TMS combined with neuroimaging techniques. Chapter 3 employs ‘on-line’ TMS applied with temporal specificity to track the passage of information through early visual cortex. Chapter 4 is a general discussion primarily concerned with the issues encountered experiments oriented towards consciousness.

Offspring of depressed mothers are at increased risk of developing a variety of psychopathologies. Risk factors and mechanisms for the development of these heterogeneous outcomes are poorly understood. Disruptions in the mother-child relationship may be one mechanism by which maternal depression increases risk for offspring psychopathology. Many adults with depression present with co-occurring psychopathology, but how these co-occurring problems affect offspring risk, or impact upon the mother-child relationship, has rarely been considered. Data were from the Early Prediction of Adolescent Depression study. Mothers with a history of recurrent major depressive disorder and their adolescent offspring were assessed three times between 2007 and 2011. Mothers completed questionnaires assessing their own depression severity and co-occurring psychopathology (anxiety, antisocial behaviour (ASB), and alcohol misuse). Offspring psychopathology (presence of psychiatric disorder, symptoms of depression, anxiety and disruptive behaviour disorder (DBD)) were assessed using the Child and Adolescent Psychiatric Assessment. The mother-child relationship was assessed using parent-rated questionnaires and an interviewer-rated speech sample. Co-occurring problems in mothers predicted new-onset psychiatric disorder in offspring; this remained significant after controlling for maternal depression severity. When investigating the specificity of risk for offspring, maternal co-occurring ASB was specifically associated with offspring DBD, whereas maternal depression severity predicted offspring depression. The mother-child relationship mediated the effect of maternal depression severity on risk for offspring psychopathology. However this was better accounted for by co-occurring maternal ASB, which predicted both maternal warmth and hostility. Maternal hostility was a specific risk factor for offspring DBD. Bidirectional effects were observed between offspring DBD and maternal hostility. Findings highlight the importance of assessing co-occurring psychopathology in mothers with recurrent depression when considering risk for offspring. Parenting interventions that reduce hostility may be beneficial for preventing or reducing adolescent DBD, particularly when depressed mothers report additional ASB. Furthermore, interventions that reduce offspring DBD may also show benefits for the mother-child relationship.

Bipolar disorder (BD) is one form of mental illness and is estimated to affect around 0.4{1.6% of the population. The disorder is characterised by recurrent episodes of mania and depression and is estimated to cost the UK economy £5.21 billion a year. Many people with BD self-monitor their behaviour to help them identify the early warning signs of an affective episode. The Personalised Ambient Monitoring (PAM) project has been conceived take ideas from existing telehealth systems and apply them to BD. By using a distributed network of discreet, unobtrusive sensors, the user's behavioural patterns can be monitored and deviations in their behaviour can be detected. In doing so it is hoped that the early warning signs can be detected and that this can be used to assist them in their self-monitoring. The PAM system is being developed by a multi-disciplinary team based at the ISVR and the School of Management at the University of Southampton, the School of Electrical and Electronic Engineering at the University of Nottingham and the Department of Computing Science and Mathematics at the University of Stirling. This thesis presents the background and motivations for the PAM project, the approach the project will take, a review of appropriate data analysis techniques and the experimental work that has been undertaken in the investigation of accelerometry for activity monitoring, the use of a wireless camera to monitor a complex environment and the use of multiple sensors to capture behaviour patterns in a technical trial. Results from the technical trial show that it is possible to process information from a variety of sensors to identity activity signatures and behavioural patterns in normal controls. When these activity patterns are trained on week-days, the results presented show that it is possible to identify weekend days as being behaviourally different.

This thesis comprises two volumes, representing the research and clinical elements submitted to the University of Birmingham in partial fulfillment of the degree of Doctor of Clinical Psychology (DClinPsy). The first volume is the research component and contains three papers. The first paper is a review of the literature from 1980 to the present day, which has examined intellectual, behavioural and psychological characteristics in participants with Sotos syndrome. The second paper is an empirical study which examines the behavioural phenotype of participants with Sotos syndrome in comparison to 3 other genetic syndromes using standardised, well validated questionnaires. The third paper summarises these in language accessible to the general public. The second volume is the clinical component containing four Clinical Practice Reports and the abstract for an oral examination. These papers represent different aspects of work conducted during clinical placements. They include a paper which formulates from two different psychological perspectives, a service evaluation, a single case experimental design and a case study.

There has been renewed interest into affective symptoms and psychological approaches to schizophrenia and other psychosis, yet no in-depth investigation as to the course, consequences or indeed psychological causes of depression in a phase specific manner in the important first episode. Our understanding of risk and aetiological processes in psychotic illness will only advance once we accurately identify the “end phenotype” of psychotic illness. This series of studies investigates the course of depression in first episode psychosis, its significance in terms of suicidal thinking, and relation to both diagnosis and other symptom domains. Depression in the acute and post psychotic phases is explored, through the importance of the awareness and appraisal of positive symptoms, and diagnosis itself. Significant findings include a pervasive nature of depression throughout the course of first episode psychosis, the predictive nature of prodromal depression and the high prevalence of suicidal acts. Appeasement and engagement with voices, subordination to persecutors and the (ineffective) use of safety behaviours drive a position of entrapment, demoralization and a lack of control. In addition negative illness appraisals are stable and may vary between cultural groups. Implications are explored, in terms of clinical practice, aetiological pathways, potential treatments and intervention strategies

Aims: To investigate the motivation for concealment and disclosure of issues related to acquired and traumatic brain injury, and the association of these motivations with a range of possible predictors and outcomes (specifically, self-esteem, social support, social avoidance, loneliness, life satisfaction and community integration). Method: Three studies were carried out. The first (N=18) was a qualitative exploration of the reasons why people with acquired brain injury and their family carers chose to disclose or conceal information about the brain injury. In the second (N=55) two questionnaires were developed from the first study (the Non-Disclosure and Self-Disclosure questionnaires). These focused on the motivations of the person with the brain injury, one addressing motivations to conceal and the other motivations to disclose. Assessments of the reliability and validity of these measures were carried out. The third study (N=65) investigated the relationships between these motivations to conceal/disclose and some possible predictors and outcomes of these motivations. Findings: In the first study, a range of motivations for disclosure (e.g. seeking social support) and for concealment (e.g. avoiding the negative reactions of others) emerged from the data. In the second study, the derived questionnaires showed good internal consistency (the Cronbach’s alpha levels are N-DQ = .92 and S-DQ = .92) and the test-retest reliability (ICC= ranged from .38 to .805). Predicted significant correlations with Brief Fear of Negative Evaluation and N-DQ1 (r=.418, n=55, p=.002) and with the Distress Disclosure Index and S-DQ2 (r=.595, n=54, p=.001) provided evidence of their concurrent validity. In the third study, as hypothesized, higher motivations to conceal (i.e. high N-DQ scores) were significantly correlated with lower self esteem (r = -.357, n = 65, p = .003 with the Rosenberg Self-Esteem Inventory); higher social avoidance (r = .345, n = 64, p = .005 with the SAD); and greater loneliness (r = .380, n = 65, p = .002 with the University of California Los Angeles loneliness scale). The results of a mediation analysis were consistent with the hypothesis that higher motivations to conceal had an impact on general life satisfaction (as measured by the LiSat-11) via the mediation of social avoidance (SAD) and loneliness scale (UCLA). However, the hypothesis related to social support was not supported. Conclusions and implications: Many people affected by a brain injury and their families are concerned about the negative and positive impact that disclosure of information about the brain injury may have. Concern about the negative impact may be associated with negative views of the self, and have a range of negative social consequences. However, disclosure in some circumstances does, in reality, have a negative impact. People with an acquired brain injury and their families may need support in learning to conceal and disclose information about their injury in a more effective way.

Thesis Overview Psychogenic nonepileptic seizures (PNES) can be defined as paroxysmal events that resemble epileptic seizures, without being associated with either abnormal electrical activity of the brain or primary physiological disturbances otherwise. It is estimated that about 10% of new presentations seen in an epilepsy clinic, and up to 30% of patients with intractable epilepsy will eventually be diagnosed as having PNES (Benbadis & Hauser, 2000). Attributing a specific ‘cause’ to PNES is conceptually and clinically contentious but it seems reasonable to say that they represent a physical expression of psychological distress involving behaviour that the patient finds difficult or impossible to control or disavows as being intentional. Most patients with PNES are initially thought to have epilepsy and treated with antiepileptic drugs (AED), sometimes for many years. Up to 40% of patients are inappropriately maintained on AEDs after the diagnosis of PNES has been established. As such, rather than being intrinsic to the condition, the widely reported poor outcomes associated with PNES may be substantially confounded by continued inappropriate medical management and iatrogenic harm. Withdrawing or continuing antiepileptic medication in patients with PNES could have important physical and psychological consequences, which may affect the prognosis of the attack disorder. If this is the case, manipulating medication following the diagnosis of PNES may have a role in the management of this disorder. The work contained in this thesis aims to explore some aspects of the effects that continuing or withdrawing AED has on the course and outcome of PNES. Following an initial general overview on the subject of PNES (chapter 1), a systematic review of the literature is presented in chapter 2; the conclusion being a lack of good quality and reliable evidence for the effects of AED treatment in patients with PNES and a need for further original research in this area. The rationale and programme of research is presented in chapter 3 Chapter 4 presents the results of a large observational study to establish the feasibility and safety of supervised AED withdrawal in patients with an established diagnosis of PNES. Only 3 of the 78 patients included reported a new type of event requiring the reintroduction of AED, and no serious medical events were reported. The study therefore shows that, with appropriate diagnostic investigations and surveillance during follow-up, withdrawal of AED can be achieved safely in patients with PNES. A randomised controlled trial presented in chapter 5 aims to evaluate the potential therapeutic effect of AED withdrawal. Of the 25 subjects recruited, 14 were randomised to immediate withdrawal (IW) and 11 to delayed withdrawal (DW). Patients randomised to IW had a significant reduction in the use of emergency treatment for PNES, and a lower proportion was found to be using emergency services. The IW group also had a sustained reduction of attacks throughout the study and by 18 months post-diagnosis 50% were attack free as compared with 27% in the DW group. The results of this exploratory trial suggested a possible therapeutic effect of AED withdrawal, with a sustained reduction of attacks following the withdrawal of medication, coupled with a significant reduction in health care utilisation and no evidence of any deterioration. The last original paper presented in chapter 6 investigates the longer term psychosocial outcome of PNES with an observational study of the 25 patients included in the RCT. This study reports a significant improvement in some psychological measures; particularly in illness representations and mood, as well as for some measures of social adjustment. The evidence presented in these three studies (chapter 4, 5 and 6) suggests that a clear delivery of the diagnosis of PNES, followed by AED withdrawal, is safe and has possible beneficial effects on the clinical and psychosocial outcome of PNES. In particular medication withdrawal in and of itself appears to be a helpful concomitant in the successful removal of an inappropriate label of label of epilepsy, reduces the potential for iatrogenic harm, may help patients to shift towards a more psychologically-based explanation, and is associated with positive psychosocial outcomes. Finally, chapter 7 gives a summary of the main findings as well as discussing methodological limitations of the current research. The clinical implications of the evidence from this body of work are also discussed, as well as possible avenues for future research in the field.

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common psychiatric disorder of childhood and manifests as symptoms of developmentally inappropriate inattention, impulsivity and hyperactivity. Although numerous deficits have been identified in ADHD, one of the most consistent findings is that patients with ADHD are more variable in the speed of their reaction time (RT) responses on neuropsychological tasks than control children. In 2008, the default-mode interference hypothesis of ADHD was introduced by Sonuga-Barke and Castellanos as a biologically plausible account of this increased within-subject variability in ADHD. This hypothesis suggests that some patients with ADHD might not effectively attenuate low frequency resting brain activity from rest to task and that these low frequency oscillations may then intrude onto task performance and cause periodic attention lapses. These periodic attention lapses would manifest as increased variability in RT data. The present thesis provided the first test of this hypothesis using DC-EEG. We assessed the power in very low frequency EEG bands (< .1 Hz) during rest and during goal-directed task performance in two samples. First was a sample of adults who self-reported either high- or low-ADHD scores, and second was a clinic referred sample of adolescent boys with ADHD and age- and gender-matched controls. We found that in both samples, low frequency EEG was generally attenuated from rest to task, but the degree of this attenuation was lower in ADHD or inattentive participants compared to controls. We also found that periodicity was evident in RT data, and that there was synchrony between low frequency fluctuations in RT data and low frequency EEG. These findings provide some initial support for the default mode interference hypothesis. The findings also highlight the potential involvement of low frequency electrodynamics in attentional processes and in the pathophysiology of ADHD.

Background: Schizophrenia has long been considered to be remarkably heterogeneous, and there have been a number of attempts to identify sub-groups of this disorder which are more homogeneous. Nevertheless, most of these have not been used in either research or clinical practice to any great extent, because diagnoses by way of these strategies would be unstable over time and impractical. In such circumstances, the vulnerabilitystress model has led to the development of a new concept of sub-grouping schizophrenia into 4 sub-types – drug related, traumatic, anxiety, and stress sensitivity. This conceptualisation is quite promising, not only because it may provide stable and practical diagnoses, but also because the terminology used therein is useful when it comes to destigmatising those who are currently diagnosed with schizophrenia. Methodology: In order to adapt this concept for practical use, this project set out to develop a semi-structured interview for making diagnoses according to it. Thereafter, psychometric properties of the interview were examined. This assessment tool was then used to confirm the longitudinal stability of the diagnosis. In order to establish the construct validity of this classification system, it was examined if the anxiety and stress sensitivity sub-groups in this system were different in terms of their external validators. Three psychopathological variables – evaluative belief, fear of negative evaluation from others, and depression – were assessed in a cross-sectional study during this process of validation. Three other clinical variables – two for the duration of hospitalization and one for the risk of self harming – were also used in a retrospective cohort study for the evaluation of the predictive value of the differentiation. Results and conclusion: Both the English and Japanese versions of the semi-structured clinical interview for psychosis sub-groups (SCIPS) were developed to sub-group patients into 4 categories, and their reliability and concurrent validity were established. The 6 month stability of SCIPS diagnoses of the drug related, anxiety and stress sensitivity sub-types was also indicated through a longitudinal study. A preliminary analysis provided little evidence of construct validity. The risk of self harming was, however, suggested as being associated with a distinction between the anxiety and stress sensitivity categories when the SCIPS was applied to a broader range of psychosis, including schizophrenia and schizoaffective disorder.

‘Voices’ or auditory hallucinations are a common phenomenon in clinical settings. In recent years, primarily in the United Kingdom, cognitive behavioural researchers have begun to turn their attention to the psychoses in general and voices and delusions in particular. Researchers have sought to develop theoretical models of voices to inform understanding and clinical intervention. Chadwick and Birchwood’s (1994) model, particularly, emphasises the role of delusional beliefs about voices. The present volume explores the role that beliefs about voices may have in understanding people’s reactions to voices and in alleviating the difficulties often associated with this experience. An initial review of the literature focused on the current evidence for a role of delusional beliefs about voices in mediating the emotional and behavioural response to voices. Evidence, from theoretical and outcome studies, was considered in assessing the validity of a cognitive model and areas for future research identified. A particular form of behavioural response to voices i.e. ‘safety behaviours’ was then investigated. Types of safety behaviours used by voice hearers were compared to those reported in persecutory delusions by an inter-rater reliability study of the Safety Behaviour Questionnaire (Freeman, Garety and Kuipers, 2001). These categories were applicable to voice hearers. The role of safety behaviours in maintaining delusional beliefs about voices, threat appraisal and distress was examined. Voice hearers with schizophrenia were compared on structured interview and questionnaire measures. Safety behaviours were implicated in the maintenance of delusional beliefs and distress. Clinical implications and areas for future research were discussed. Finally, ethical, methodological and clinical issues were considered along with personal reflections on the research process in the reflective research review.