This doctoral study examines the aspects of psychological trauma and investigates why singular explanatory models fail compared with a holistic approach. Part of this integrated approach includes the development of a benchmarked psychometric test, the Sherry Trauma Assessment Test [STAT]) (Copyrighted © Richard Sherry 2011). The test’s reliability was evaluated using Chronbach’s alpha (p< 0.001 levels of significance), which these findings were crosschecked with the findings from eleven other psychometric tests to standardise the results. In comparing the data sets, the STAT test project data was used to both answer fundamental questions within the field of clinical trauma psychology and confirm the reliability of the newly developed psychometric test. Furthermore, the information was collected and used to derive a principle component analysis (PCA) to help in developing a model to support current thinking within the social neuro-scientific arenas as well as to better organize clinical psychology assessment and treatment approaches. These findings have important implications on how trauma, in particular, the human neuropsychological learning process, is addressed. This psychometric foundation was then used to develop this newer model and adaptive tele-medicine platform (Zielinski et al., 2006). This multidisciplinary integration of information, expertise and models, has served to clarify the effects of maturation in relationship to traumatic response and helped to refine the understanding of how traumatic phenomena serves to fragment the integration of embedded systems, and what can be done to reverse these problematic processes in order to replace them with positive cycles of development. The STAT test findings have shown statistically significant results (p< 0.001 level), which provide quantitatively grounded evidence in support of this psychometric measure and improve clinical assessment and treatment approaches. The theoretical model of the STAT test is included in the concept of Integrated Systems Healing, which was developed independently, but has similar theoretical roots in Goetz and Caron’s (2005) bio-psychosocial model of the Systemic Healing used in the treatment of sick children. The author describes further conceptual developments within the concept of Integrated Systems Healing (Copyrighted © Richard Sherry 2011) to include the holistic systems approach, which could be used for a large-scale treatment with specific interacting components of Integration, Compassion, Developmentally scaled interventions, and Sustainability or the ICDS Model (Copyrighted © Richard Sherry 2011). This project has evolved improved strategies for integrative assessment, feedback, and holistic approaches for learning and programme development to improve people’s lives. These foundations of improved internal and external dynamic assessment connect to flexible tele-health approaches, using defined cut-off scores, elearning modules, and strategies for checking and reassessment. Further work links and integrates processes to identify and reduce vulnerability and strengthen resiliency and support.

This volume presents research into family issues in the context of Obsessive-compulsive disorder (OCD). The first section is a focused review of the literature concerning the effects of OCD on family members and on within family processes. While OCD has long been regarded as a disabling condition for sufferers, this review offers a critical evaluation of several new strands of research into its impact on the lives of relatives, with the aim of identifying important clinical implications and offering direction for future studies. An empirical investigation into beliefs about having children in the context of maternal OCD forms the second part of this thesis. As theoretical conceptualizations and recent research suggest a complex relationship between OCD and parenthood, this cross-sectional study aimed to explore sufferers' perceptions of the effects of OCD on parenting abilities and on the child, as well as beliefs about the impact of parenthood on OCD symptomatology and coping abilities. Women with OCD were compared to anxious and healthy controls, and the predictors of parenting perceptions were also examined. The final section of Volume 1 comprises a critical appraisal of this study with reflections on the rationale for the research, the methodological choices that were made, and the clinical as well as scientific implications of the results.

This thesis considers the prevalence of autistic traits in disorders that are not traditionally associated with autism. Part I is a review of studies examining the presence of autism spectrum disorders (ASD) and autistic traits amongst people who have a non-ASD diagnosis. This includes a critical evaluation of the methodological and conceptual issues pertaining to current research evidence. In conclusion, evidence for the presence of elevated ASD traits is highlighted. However, further work is required to accurately estimate the true prevalence and clinical implications. Part II examines the possibility of undetected ASD in young people with restrictive eating disorders (ED). This was done using a case-control design involving three IQ-matched groups: (1) ED (n =22); (2) typically developing (n =24); (3) ASD (n = 20). Joint recruitment and data collection was undertaken with Aafke Ninteman who examined shared neuropsychological traits (Ninteman, 2010). No significant differences were found between typically developing controls and individuals with ED on a measure of the autism triad. However, the ED group showed elevated scores on a measure of restricted and repetitive behaviours of a similar severity to the ASD controls. Although these findings refute the notion that diagnostic threshold level ASD is prevalent in individuals with ED, they do present an intriguing picture of elevations in a fraction of the autism triad. Further research is required to determine whether these elevations reflect autism symptomology or merely present as autism-like behaviours. Part III presents further methodological issues pertaining to the study. Moreover, personal reflections on the research process are considered as well as wider implications for research and clinical practice.

This thesis is presented in three parts. Part one reviews published studies utilising the 'trauma film paradigm'; an experimental analogue method for investigating the effect of pre-, peri-and post-trauma variables on PTSD symptomatology. It reports results from the reviewed trauma "film paradigm studies in relation to intrusive memories and compares these findings with clinical literature and cognitive processing models of PTSD. Part two presents the empirical paper; an investigation of the effect of rumination on analogue-PTSD intrusive memories and mood using the trauma film paradigm. Results indicate that both trauma-and non trauma-related rumination affects intrusions and negative mood. This was the first experimental study to specifically examine the role of rumination in the maintenance of symptoms. Findings support clinical research regarding the effects of rumination in persistent PTSD. The findings are presented in the context of theoretical explanations for the effect of rumination. Strengths and limitations of the study, as well as clinical implications, are discussed. Part three is a critical appraisal of the research study, which draws on the literature review presented in part one, and reflects in more detail on the methodological and conceptual strengths and limitations of the research. It also discusses the development of ideas underlying the study and the implications for future trauma film paradigm studies and clinical treatment.

The following thesis is comprised of three parts. Part one is the Literature Review. This section reviews relevant papers with the aim of answering the question "can we enhance Cognitive Behavioural Therapy (CBT) for anxiety disorders using medication". The second part is the Empirical Paper. This details a randomised, placebo-controlled study investigating the effects of combining D-cycloserine (DCS) with cue exposure in a population of heavy social drinkers. Outcome measures of subjective craving and attentional bias are examined to assess if DCS can enhance the efficacy of cue exposure therapy in this population. The study presented in the Empirical Paper was conducted jointly with another trainee, Lydia Rodney (D.Clin.Psy, 2010). See Appendix A for further details. Finally, part three is the Critical appraisal, which includes reflections on the study presented in the empirical paper and, more broadly, on the research process in its entirety.

Part 1-The Literature Review explores the topic of attentional bias which is thought to be a component of many anxiety disorders. A review of the literature on dot-probe studies of anxious individuals which used faces as stimuli found 24 studies. Studies of both socially anxious and generally anxious individuals suggest attentional bias in the initial, orienting stage of attention, which is increased by conditions of social threat. The review concludes that attentional vigilance for threat is a consistent feature of anxiety disorders including both social anxiety and GAD. There is little or no evidence to support the view that anxiety disorders are characterised by attentional avoidance of threat faces, as measured by the dot-probe paradigm. Part 2 -The Empirical Paper reports on a study of facial affect recognition and attentional bias in psychosis-prone participants. Data collection was shared with another trainee (see Appendix D). There was no difference in facial affect recognition between the two groups. The high schizotypy group did however display a significantly greater attentional bias score at 2000ms, and a significantly lower attentional bias score at lOOms, than the non psychosis-prone group. The limitations, clinical and research implications of this study are discussed. Part 3 -The Critical Appraisal describes the selection of the topic, ethical and theoretical considerations, an appraisal of the design and methodology, as well as reflections on the research process as a whole.

The exact pathophysiology of major depressive disorder (MDD) has yet to be fully elucidated. The belief that depression is strictly a disorder of monoaminergic consequences is undergoing great reconsideration due to the lack of efficacy of the current pharmacotherapeutics. There is compelling clinical literature implicating a role for cytokines in the pathophysiology of MDD. IL-6 and IL-1β are pleiotropic inflammatory cytokines that have been reported to be elevated in patients with MDD. The present studies were undertaken to investigate the relationship between IL-6 and IL-1β in animal models of depressive-like behavior. In rats subjected to learned helplessness or a submissive behavior paradigm, analysis of brain tissue homogenates revealed elevated levels of IL-6 protein in the absence of elevations in IL-1β. Central administration of recombinant mouse IL-6 produced depressive-like phenotypes in mice in the absence of IL-1β induced increases in brain tissue or IL-1β related sickness behavior typical of a general CNS inflammatory response. These data therefore suggest that IL-6 and IL-1β have distinct roles in mediating depressive-like and sickness behaviors, respectively. Administration of the SSRI fluoxetine in the presence of centrally administered IL-6 failed to produce the expected antidepressant-like response in mice. Further, administration of fluoxetine to mice with endogenous overexpression of brain IL-6 (MRL/MpJ-Faslpr/lpr (LPR mice)) failed to produce the expected antidepressant-like effect relative to fluoxetine-treated WT control mice (MRL/MpJ+/+). Interestingly, blockade of IL-6 trans-signaling by co-administration of a gp130/Fc monomer or an anti-mouse IL-6 antibody with IL-6 prevented the IL-6-induced depressive-like behavior as well as attenuated IL-6-induced increases in brain protein levels. Taken together these data indicate that depressive-like behavior may be related to elevated levels of IL-6 in the brain and suggest that modulation of the IL-6 signaling pathway by way of preventing de novo IL-6 production may have therapeutic potential for treatment-resistant depression.

Cognitive behavioural therapy (CBT) for common mental health problems is increasingly being delivered by telephone, over the internet and via guided self-help. This thesis examines telephone-delivered interventions for anxiety and depression and is presented in three parts. Part I is a literature review of the effectiveness of telephone interventions for anxiety and depression. Sixteen studies met criteria for the review. Overall, study quality was good and there was reasonable evidence that telephone interventions show promise in reducing symptoms of anxiety and depression. Further research is required to determine the characteristics of people who find telephone-delivered interventions beneficial. Part II presents the findings from a qualitative study of recipients’ experiences of a 14-week telephone-delivered CBT group for anxiety disorders. Seventeen people completed a telephone interview. Interview transcripts were analysed using the ‘framework’ approach and yielded 10 themes organised into three domains. There were therapeutic benefits from taking part in the groups, even in the absence of symptom change. However, a number of barriers and challenges (e.g. difficulties in connecting with others over the telephone) sometimes prevented people from making full use of the groups. Further research is needed to understand the impact of delivering group CBT by telephone, in order to guide the delivery of similar low-intensity interventions for anxiety. Part III is a reflection on the research process and focuses on the impact of using the telephone for semi-structured interviews, the advantages and challenges of conducting research with external organisations, and the implications for the delivery of low-intensity interventions.

This thesis discusses four studies, looking for genetic determinants of common epilepsies: 1) A genome-wide association study (GWAS) of partial epilepsies (PE), which was the first published GWAS in the field of epilepsy (Chapter 4). 2) A GWAS of mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) (Chapter 5). 3) A case series of patients with refractory MTLE, operated and found to have large microdeletions at 16p13.11, 15q11.2 and others (Chapter 6). 4) A clinical, genetic and neuropathologic study of a series of patients with Dravet syndrome (DS), diagnosed as adults, including genotype-phenotype correlation analysis (Chapter 7). The main findings include: 1) The GWAS of PE has not yielded any genome-wide significant association with common genetic variants, possibly because of insufficient power and phenotypical heterogeneity. It is, however, a strong foundation for further studies, illustrating the feasibility of large multicentre GWAS in the epilepsies (Chapter 4). 2) The GWAS of MTLEHS yielded a borderline genome-wide statistically significant association with three common genetic variants close or intronic to the SCN1A gene, especially in MTLEHS with antecedents of childhood febrile seizures (Chapter 5). 3) Large microdeletions at 16p13.11 and others were found in patients with MTLEHS and not only in idiopathic non-lesional epilepsies. Good outcome after resective epilepsy surgery is possible in “typical” MTLEHS even with large microdeletions (Chapter 6). 4) The identification of a cohort of adults with DS, not diagnosed as children, allowed the description of long-term evolution through adulthood and recognition of clinical features shared later in the evolution. Over sixty percent had SCN1A mutations. Missense mutations were more frequent in patients who survived through adulthood, with truncating mutations and large deletions only found in those who died in early childhood. Medication changes after diagnosis led in some cases to better seizure control, cognition and quality of life. Further evidence for DS as encephalopathy came from post mortem histopathology, with no neuronal loss found in cerebral cortex or hippocampus.

Identifying participation restrictions in individuals with communication disorders might provide a better understanding of their ability to take part in different life situations, and possibly improve their rehabilitation process. In this research, the Arabic Communication Participation Scale (ACPS) was developed to measure communication participation restriction in Arabic speakers with progressive dysarthria. This scale is different from other communication participation scales because it is intended to measure communication participation from the perspectives of individuals with communication disorders and their communication partners. The development of the ACPS went through several phases, starting from selecting relevant items to form the scale, followed by the translation and cultural adaptation of the scale for it to be applicable to this research-targeted population. In the pilot study, Saudi speech therapists, Arabic speakers with progressive dysarthria, and their communication partners, evaluated the scale’s usability and applicability. Field testing of the ACPS was then applied to 50 Arabic speakers with progressive dysarthria and 50 control participants, divided equally into two groups (25 Arabic speakers with progressive neurological diseases but no communication disorders, and 25 healthy speakers). The psychometric properties of the ACPS were tested. The relationship between individuals with progressive dysarthria and their communication partners, in measuring communication participation, were then investigated. Finally, examples of factors affecting communication participation were presented. This study showed that the ACPS was able to detect degrees of communication participation restrictions in Arabic speakers with progressive dysarthria. Cultural adaptation was found to be as important as translation to assure the sensitivity of the scale in measuring its intended concept. The ACPS has acceptable psychometric properties. It showed a positive significant relationship between Arabic speakers with progressive dysarthria and their communication partners. Finally, although a positive relationship was observed between the presence of a speech disorder and restrictions in communication participation, the findings showed that other factors such as (physical disability) could affect communication participation. Future research is needed to investigate the possible effect of a different types of factors associated with Arabic speakers living in Saudi Arabia. Examples include measuring the effects of psychosocial factors, environmental factors and surgical/medication effects on communication participation restrictions.