ZNF804A was (at the time this work started) one of only a few robustly implicated schizophrenia susceptibility genes, due to replicated genome-wide significant evidence for association between a polymorphism in the gene and schizophrenia. Determining the function of the ZNF804A protein, which is currently unknown, may provide a way of elucidating the pathophysiology of this relatively common, complex disorder. Based on the hypothesis that the ZNF804A protein regulates gene expression or splicing, the aim of this thesis was to identify genes that exhibit altered expression or splicing in brain tissue from mice in which the orthologue Zfp804a carries a nonsense mutation. No robust evidence was obtained that showed the effects of the mutation on differential expression in individual genes. Although this finding does not support the hypothesis that ZNF804A acts directly to regulate gene expression, the results may reflect the possibility that effects on gene expression may be too subtle to be detected using the methods applied. Evidence was obtained to show the mutation affected the alternative splicing of a number of individual genes, which could suggest a role for ZNF804A in the direct or indirect regulation of alternative splicing. Through RNA sequencing, I identified a novel transcript in Zfp804a with an alternative exon upstream of the Refseq exon 1. I also showed that a proportion of the significant splicing differences identified in mutants were artefacts of strain differences in gene sequences that are likely to affect the efficiency of hybridisation on the exon array. Genes identified as differentially spliced between mutants and wildtypes were enriched in axon guidance and cell adhesion pathways, both thought to be important during development. The findings of this thesis suggest the novel hypothesis that ZNF804A effects risk for schizophrenia via aberrant splicing in the above pathways that are critical to normal brain development. Further studies with increased power are required to understand the effects on gene expression.

This research examined therapeutic approaches to trauma and post traumatic growth and recovery as a result of brief psychological intervention. Chapter one is a critical review of current therapeutic approaches used in the treatment of trauma and post traumatic stress disorder, PTSD. The PTSD treatment literature indicates that the therapy most rigorously assessed and currently recommended by the National Institute for Clinical Excellence (NICE) is trauma-focused Cognitive Behavioural Therapy and Eye Movement Desensitization and Reprocessing. Despite this, the literature review indicated that other forms of therapy have been effective in reducing the symptoms of PTSD. The research indicated that clinicians are successfully using psychodynamic, integrative and person centred approaches in both an individual and group therapy format. Regardless of therapeutic approach used, issues of client motivation, timing of therapy and therapeutic alliance were important determinants in outcome. Chapter two is an empirical study, which focuses on the effect of brief psychological intervention on recovery from trauma. A mixed methodological design was used and five participants took part in the research. The results indicated that those participants whose trauma symptoms reduced had experienced recovery from their trauma. Participants cited underlying beliefs towards adversity, personal and contextual factors as important in facilitating recovery. Recommendations for further research and clinical implications were discussed. Chapter three provides the authors reflections upon the research process and methodological and ethical issues that arise when carrying out qualitative research with a trauma population.

Obesity is one of the most significant health concerns across the world, particularly in developed countries, and there is no evidence to suggest that obesity is becoming less prevalent. There are many physical, psychological and social consequences from being obese. Nevertheless, interventions to date have been generally unsuccessful at providing long lasting effects. Furthermore, there has been a general lack of attention given to non-weight factors relating to overall well-being. The literature review presented in chapter 1 critically evaluates the research to date exploring the efficacy of mindfulness-based interventions for overweight and obese adults. The promising initial indications that this ‘third-wave’ approach offers are discussed within the methodological limitations of current research. Clinically, the approach appears to have potential, although future research should aim to have greater consistency in defining what constitutes a mindfulness approach. The empirical paper presented in chapter two explores how the attributions made by trainee teachers about the cause of weight gain may impact on helping behaviour in a school setting. A mixed methodology questionnaire design is used. This incorporates a vignette about a significantly overweight child and a series of open ended questions to explore the factors that trainee teachers see as key considerations for making interventions for obese children more effective. The results are discussed within the context of how healthcare professionals may offer a valuable role in training and coordinating intervention efforts. The final chapter is a reflective paper summarising some personal, professional and academic experiences that occurred during my thesis. Current and alternative approaches taken towards childhood obesity are discussed and reflected upon.

Gender identity is an integral part of who we are and can have a huge impact on our functioning, behaviour, and psychological well-being. For years, researchers and theorists have studied the developmental course of gender identity including why, how, and when it is formed, and how it shapes our neurobiology and psychology. The first chapter of this thesis reviews existing literature on the relationships between gender identity and psychological well-being across the course of childhood. The review indicates that psychosocial adjustment and self-worth are highest when children feel secure in their gender identity, yet able to explore gender atypical options. Feelings of gender atypicality or dysphoria are associated with poorer psychological outcomes and vulnerability to mental ill health, particularly depression.The review highlights various methodological limitations within the literature and suggests improvements such as using more socially diverse samples. Chapter two presents an empirical study exploring gender and identity in adult men with Asperger’s Syndrome capturing their perceptions of masculinity, gender-typed behaviours, relationships, and societal influences. Interpretative Phenomenological Analysis of the data suggests that for participants, identifying with male gender provides a platform for fitting in by allowing them to learn from societal stereotypes and rehearse playing ‘male’ roles. Participants displayed ambivalence in their feelings of being drawn to the perceived safety of females but resenting the ‘feminine’ side of themselves. Recommendations are made for psychoeducation for Gender identity is an integral part of who we are and can have a huge impact on our functioning, behaviour, and psychological well-being. For years, researchers and theorists have studied the developmental course of gender identity including why, how, and when it is formed, and how it shapes our neurobiology and psychology. The first chapter of this thesis reviews existing literature on the relationships between gender identity and psychological well-being across the course of childhood. The review indicates that psychosocial adjustment and self-worth are highest when children feel secure in their gender identity, yet able to explore gender atypical options. Feelings of gender atypicality or dysphoria are associated with poorer psychological outcomes and vulnerability to mental ill health, particularly depression.The review highlights various methodological limitations within the literature and suggests improvements such as using more socially diverse samples. Chapter two presents an empirical study exploring gender and identity in adult men with Asperger’s Syndrome capturing their perceptions of masculinity, gender-typed behaviours, relationships, and societal influences. Interpretative Phenomenological Analysis of the data suggests that for participants, identifying with male gender provides a platform for fitting in by allowing them to learn from societal stereotypes and rehearse playing ‘male’ roles. Participants displayed ambivalence in their feelings of being drawn to the perceived safety of females but resenting the ‘feminine’ side of themselves. Recommendations are made for psychoeducation for professionals and parents of children with Asperger’s syndrome around potential gender identity confusion. The third chapter presents a reflective review of the author’s experience of conducting the research. The paper provides a personal insight into issues pertaining to methodological processes, relationships with participants and associated emotions.

This thesis focuses on theory ofmind (ToM) and executive function (EF). Psychosocial treatments aimed at enhancing ToM skills are explored. Impairments in ToM in acquired brain injury (ABI) and a possible relationship to performance on tests ofEF is investigated. The literature review explores whether ToM abilities can be enhanced through psychosocial treatments in typically developing children and across various clinical populations. Attention is paid to whether reported improvements found through various approaches, can be generalised to other tasks, or real life situations to indicate whether a conceptual change has occurred. The implications are discussed in terms of future research and clinical implications. The empirical paper explores whether individuals with ABI can pass ToM tasks and whether this is related to performance on tests ofexecutive function (EF). Performance is compared and contrasted with neurologically healthy controls. Findings indicate that individuals with ABI performed significantly poorer than the neurologically healthy group. A limited relationship was found between tasks ofToM and tests ofEF. There were no real differences in this relationship between the two groups. The implications are discussed in terms of a need for further research and clinical implications. The reflective paper explores the role ofreflection during the research process. Reflection is focused on academic and clinical experiences, dreams that occurred during the research process and presentation ofparticipants during data collection. Application of some ofthese reflections to clinical practice is discussed.

Chapter one considers the literature on sexuality and long-term relationships in people with autism spectrum disorders (ASD). The research has many methodological flaws, however it is clear that sexuality and long-term relationships are important to people with ASD. Their difficulties with social interactions may impact on the development of sexuality, and this can lead to inappropriate sexual behaviours and difficulty initiating relationships. It is suggested that further research would add to our understanding of sexuality and relationships for people with ASD. It is recommended that services should focus on supporting the development of appropriate sexual behaviours, and improving the social support networks of individuals in relationships. Chapter two explores the experiences of friendship in six adults with Asperger syndrome or high functioning autism (AS/HFA). Interpretative Phenomenological Analysis is used to identify themes from the interviews. The super-ordinate themes are: defining friendship, maintaining friendships, difference, increasing selfawareness and maturity, and future desires. The participants particularly highlight the importance of friendship. The results are discussed in relation to existing research, and limitations of the study are considered. It is suggested that interventions by statutory and voluntary organisations should focus on early diagnosis of AS/HFA and the facilitation of friendships for adults. Chapter three provides a reflective account of conducting qualitative research with people on the autism spectrum. Reasons for the limited use of qualitative research with this group are considered, and challenges to the research process are discussed. It is argued that people on the autism spectrum have valuable contributions to add to our understanding of friendship, due to their focus on detail. The idea that autism should be seen as a difference rather than a disability is briefly discussed with reference to the empirical paper.

The following thesis consists of three papers; a literature review, an empirical paper and a reflective paper. The literature review summarises current knowledge regarding the efficacy of systemic family therapy in neurorehabilitation. Studies investigating the impact of brain injury on the family suggest that all family members should be included in their injured relatives’ rehabilitation programme due to the risk of developing relational difficulties. In view of this, family therapy has become increasingly popular amongst Clinical Psychologists and other professionals working in neurorehabilitation. This review aims to critically evaluate the efficacy of systemic family therapy within neurorehabilitation. Methodological considerations and implications for future research are discussed, as well as clinical and service implications. The empirical paper explores changes in children’s relationships when a parent acquires a brain injury. The findings of the study highlight the positive and negative changes children experience in their relationships as a result of their parents’ acquired brain injury (ABI). Results are discussed in relation to the current literature, consideration of the strengths and limitations of the research, clinical implications and recommendations for future research. The reflective paper discusses the researcher’s own experience of carrying out the research. The researcher utilised the ‘Heartstrings’ activity used in the empirical study to help them reflect on changes in their relationships throughout the research process.

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases. However, the aetiology of AD is still unclear and there is currently no cure. In order to develop new therapeutic strategies more basic research into the underlying mechanisms leading to cognitive impairment is needed. This thesis uses the Tg2576 mouse model to examine the effects of amyloid pathology on hippocampal network activity and memory, and to assess the therapeutic effects of exercise as a lifestyle intervention against amyloid-induced cognitive decline. The hippocampal network is made up of different structural sub-regions, dentate gyrus (DG), CA1 and CA3, each of which plays a different role in memory encoding and retrieval. An analysis of c-fos expression was carried out followed by structural equation modelling to assess neural activity in each sub-region when Tg2576 and wild-type control mice explored a novel or familiar spatial environment. In young transgenic mice there was a reduction in DG engagement when encoding spatial novelty compared to controls. In aged mice deficits in DG engagement were seen in both genotypes. The influence of amyloid-induced hippocampal network alterations on cognition was assessed on a novel task designed to test configural integration of cues relating to episodic memory. An analysis of c-fos expression in normal mice revealed that this task was also DG dependent. Marked deficits in episodiclike memory were seen in older transgenic mice, however, in contrast to hippocampal activity, no deficits were reported in young transgenic mice compared to wild-types. In the second section of this thesis the hypothesis that long-term voluntary exercise can reduce cognitive decline was tested. Exercise improved cognition in transgenic, but not wildtype mice, in tests of working and reference spatial memory. In addition, a deficit in configural memory for episodic information was reversed in transgenic mice by exercise. The effect of exercise on amyloid levels and DG neurogenesis was assessed, as these are putative molecular substrates which may be altered by exercise leading to improved cognition. However, exercise did not significantly influence either of these measures. These data indicate sub-region specific changes in hippocampus network activity in the Tg2756 model of amyloid pathology, which may underlie deficits in spatial and episodic-like memory. Furthermore, prolonged exercise reduced cognitive decline in this model, and may be a useful therapeutic intervention to prevent or delay the onset of AD in at-risk patients. However, the precise molecular mechanisms by which exercise exerts its beneficial effect on memory remain to be established.

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.

Attention refers to the cognitive processes that prioritise a subset of available sensory information for enhanced processing, and which can be directed towards spatial locations, object features, time, or other aspects of the environment. While the majority of research has focused on studying attention within sensory modalities, a growing body of evidence has demonstrated that attention interact with multisensory processes. Several neuroimaging studies have shown that higher cortical regions activated during attention to multiple sensory modalities overlap significantly with the dorsal and ventral frontoparietal regions activated during visual attention tasks. This evidence has led some researchers to propose the existence of supramodal frontoparietal system that controls the deployment of attention across various sensory modalities. Although influential, this hypothesis has been challenged by other studies that discovered evidence for modality-specific regions in the parietal cortex. In this thesis, I investigated the generality and specificity of the frontoparietal network associated with multisensory spatial and feature-based attention, in vision and touch, by applying multivoxel pattern analysis (MVPA) to fMRI data. Recent studies have successfully demonstrated that MVPA methods could be used to discriminate various experimental conditions from weak distributed patterns of activity within overlapping cortical regions found by univariate fMRI analysis. Here, I applied similar logic to examine overlapping frontoparietal regions activated during multisensory attention. Contrary to the supramodal hypothesis, the results supported the existence of modality-specific systems in the posterior parietal cortex during both attention to spatial locations and stimulus features. Additional evidence for modality-specific processes was also indicated in the patterns of top-down modulatory activity in visual cortex. Overall, the current findings supported the view that both modality-specific and potentially supramodal frontoparietal regions work in concert to selectively bias activity in sensory cortical regions during various states of attention.