The work presented in this thesis focuses on a behavioural and histological characterisation of the HdhQ111 mouse model of Huntington’s disease (HD). Numerous mouse models of HD are currently available; however, before their use, each must be fully understood, validated and characterised, which will allow the most appropriate model to be used in scientific research. Chapter 1 provides a general introduction. Chapter 2 states the materials and methods used in this thesis. The work presented in Chapter 3 encompasses an extensive longitudinal immunohistological characterisation of the HdhQ111/+ mouse model, which includes immunohistochemical stains from animals at 3, 6, 9, 12, 15 and 18 months of age, to understand the development of the underlying neuropathology associated with this mouse model. Chapter 4 builds on the knowledge gained from the previous chapter to explore the longitudinal progression of motor symptoms associated with the HdhQ111/+ mouse model. In Chapter 5 a longitudinal operant battery was conducted to explore cognitive dysfunction in the HdhQ111/+ mouse model. Operant tests of motivation, attention and implicit learning were conducted longitudinally at 6, 12 and 18 months of age. Chapter 6 uses the knowledge gained from Chapter 5 to explore the effects of operant pre-training, at a young age, and the impact that this has on latter operant task performance and the development of the disease phenotype at an older age. To further understand the cognitive deficits observed in the HdhQ111/+ mouse model, Chapter 7 presents the creation, optimisation and utilisation of an operant delayed matching and delayed non-matching to position (DMTP/DNMTP) task, which could be used to test working memory and reversal learning in mouse models of neurological diseases including HD. Chapter 8 includes a general discussion of the work presented in this thesis. The studies presented within this thesis demonstrate the development of a clear neuropathological profile as well as significant motor and cognitive deficits in the HdhQ111 mouse model of Huntington’s disease. We can therefore conclude that the HdhQ111 mouse model is a valid mouse model for investigating the pathogenic mechanisms of Huntington's disease and for testing therapeutic interventions in HD.

Research suggests that people may hold positive explicit attitudes whilst holding negative implicit attitudes towards Lesbian and Gay (LG) people. While this seems evident amongst the general population, a previous systematic review (e.g. Boysen, 2009) only identified one study investigating explicit and implicit attitudes towards LG identities amongst counsellors. There are no similar systematic reviews using samples of psychologists, so this review aims to bridge that gap by conducting an analysis on studies completed between January 1990 and May 2013. In this review were included studies that: a) investigated attitudes of psychologists or psychologists-in-training towards LG people; b) included original data and findings; c) included comparison groups; and d) had been carried out in countries where homosexuality is not criminalised and where there is anti-homophobia legislation currently in place. Of the initial 933 studies identified, 18 met the main inclusion criteria. Designs were diverse and used a range of attitude measures. Only one study investigated implicit attitudes. Despite the diverse range of designs and measures it appears that positive attitudes to LG people may be conditional upon several factors, including gender, religiosity, socialisation, training, and level of education of psychologists. Training courses can potentially address such needs, but these need to be designed specifically to address LG topics, since general training on diversity topics may not promote positive implicit attitudes to LG people.

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.

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.

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.

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.

Epilepsy, which affects 50 million people worldwide, is a chronic neurological condition characterized by a predisposition to generate spontaneous seizures. Antiepileptic drug resistance is a significant problem, the causes of which are poorly understood. Inflammation is purported to play a pathological role in the development of epilepsy following brain insult. High mobility group box-1 (HMGB1) has been implicated in the development of seizures and epilepsy in preclinical models and human studies. HMGB1 undergoes post-translational modifications, including acetylation and redox changes, which dictate its inflammatory extracellular function. Novel inflammatory blood biomarkers such as HMGB1 that are intricately involved in the epilepsy disease process per se may act as stratification markers to identify patients who may benefit from immunomodulatory interventions. This thesis aimed to characterise the role of HMGB1 in seizures and epilepsy and its utility as a clinical biomarker. Analysis of 24 healthy volunteers undergoing a 24-hour blood-sampling study did not demonstrate any significant circadian fluctuations in serum HMGB1. No intra or inter-subject variability was also observed in the biomarker. A further study involving patients with idiopathic intracranial hypertension (IIH, n=18), neuroinfection (n=15) and Rasmussen’s encephalitis (n=10) showed that there was no correlation between serum and cerebrospinal (CSF) fluid levels of HMGB1, regardless of blood brain barrier integrity. Subgroup analysis of bacterial meningitis showed that both CSF and serum HMGB1 was significantly elevated (as compared to IIH). Furthermore, CSF HMGB1 was more than 10-fold higher in those with bacterial (n=6) rather than viral meningitis (n=8). The expression pattern of HMGB1 acetylation and redox isoforms in brain and blood was examined in three distinct preclinical models of seizures and epilepsy including recurrent seizures and status epilepticus in the kainate-model, single seizure in the maximal electroshock test (MES) and chronic spontaneous seizures in the pilocarpine epilepsy model. In response to kainate-induced seizures, in both brain and blood, an early rise in non-acetylated and reduced HMGB1 isoforms was demonstrated consistent with functional chemotaxis. This was followed by a delayed 6-fold rise at 24 hours in brain of the acetylated, disulphide inflammatory form of HMGB1. In serum, significant expression of the inflammatory isoforms was seen after 14 days, possibly coinciding with the onset of spontaneous seizures. Inflammatory isoforms of HMGB1 were not identified within the first 24 hours following isolated MES-seizure in mice. Serum, but not brain, total HMGB1 was significantly elevated (by 311%) in chronic epileptic mice experiencing regular spontaneous seizures; however the contribution of the different isoforms remains to be elucidated. In humans with epilepsy, compared to both healthy controls (1.11±0.07ng/ml, p < 0.0001) and those with well-controlled epilepsy (1.25±0.15ng/ml, p < 0.0001), mean baseline total HMGB1 was significantly higher in patients with drug-resistant epilepsy (8.70 ±0.47ng/ml). Acetylated HMGB1 was observed in drug-resistant patients alone; with a subset expressing the disulphide inflammatory form. In conclusion, these studies have provided insight into the potential of novel, circulating isoforms of HMGB1 to serve as mechanistic biomarkers of established drug-resistant epilepsy in humans. There is a need for future studies to examine the prognostic value of HMGB1 isoforms following first seizure for the early identification of those at greater risk of developing drug resistance and ultimately, those who may benefit from immunomodulatory interventions.

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.

Background: Patient-provider communication (PPC) influences patients’ health trajectories and general well-being, and its principles are taught and assessed during UK medical education. However, providers differ in their PPC, specifically of emotive issues. Two psychological characteristics have been proposed as potential influencers of PPC: attachment style and emotional intelligence (EI). Aim: To explore the relationships between providers’ attachment styles, EI and PPC. Procedures: Three empirical studies were conducted in one UK medical school/deanery. Study 1 investigated the influence of 1st year medical students’ (n = 200) attachment styles and EI on their PPC in an Objective Structured Clinical Examination (OSCE). Study 2 replicated Study 1 with 2nd year medical students, consulting in a more ‘demanding’ OSCE (n = 296). Study 3 studied junior doctors (n = 26) consulting in General Practice with real patients (n = 173). Attachment was assessed using the Experiences in Close Relationships: Short Form questionnaire, whilst EI was assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test. PPC was assessed using OSCE checklists (Studies 1 and 2) and a patient satisfaction measure (Study 3). Consultations were videoed and coded with the Verona Coding Definition of Emotional Sequences, which quantifies patients’ expressions of emotion and associated provider responses. Analyses: Data were analysed using structural equation modelling (Studies 1 and 2) and multilevel modelling (Study 3). Results: In all studies, providers’ attachment styles and EI influenced their PPC. In Studies 1 and 2, EI mediated the influence of attachment on PPC, accounting for 7% and 14% of the variance in students’ OSCE scores respectively. In Study 3, doctors’ attachment and EI influenced the number of emotive cues received from patients; neither influenced patient satisfaction. Limited relationships were observed between providers’ attachment or EI and their responses to patients’ emotions across all studies. Conclusions/Implications: Attachment and EI independently influence PPC, but EI may mediate the negative influence of attachment. Whilst attachment is relatively stable throughout the life course, EI can be developed throughout undergraduate medical education, thus these data have potential educational implications. Further research is recommended to explore and validate these findings within the wider context of the clinical encounter.

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.