Background: Theory of mind and executive function deficits have been implicated in a wide range of neurological conditions, including traumatic brain injury (TBI) and autism spectrum disorder (ASD). Uncertainty remains about the degree of overlap of these functions, as well as the mechanisms that may be involved in specific disorders. The role of other processes, such as anxiety, has also not been considered. Aims: To investigate the role of anxiety in individuals with ASD and TBI in their executive function and theory of mind abilities. Methods: A prospective between groups design was used to compare ASD and TBI groups. Relaxation training was implemented and individuals were compared pre- and post- relaxation on measures of executive function and theory of mind. Results: Pre-relaxation scores indicated the ASD group had significantly higher anxiety than the TBI group, but with relaxation improving anxiety in both groups. Significant interactions of executive function, theory of mind and group were found, with the ASD group scoring higher after relaxation. A significant correlation was also found between executive function and theory of mind, but only in the ASD group. Conclusions: The present results suggest anxiety may play a significant role in the executive function and theory of mind deficits observed in ASD. TBI may involve different mechanisms which impact on functioning. Applications: The findings raise important implications for intervention and the potential to develop executive function and theory of mind skills in ASD.

A body of literature has examined the understanding adults with intellectual disabilities have of their disability, their awareness of stigma and experiences of stigmatised treatment. The findings across these studies have however been difficult to reconcile. While a number of researchers reported that participants did not appear to be aware of their disability, others found that participants were aware of their disability and were sensitive to the stigmatised treatment they received from others as a result. The methods used by previous researchers have been largely verbal and it is suggested that such methods may have placed constraints on the abilities of people with intellectual disabilities to express themselves. Thus, the mixed findings may in part be accounted for by the reliance on verbally based methods of enquiry. As a result of the previous research having been carried out with adults, little is known about the perceptions children with intellectual disabilities have of their disability or their awareness of social stigma. It is important to know about children's perceptions because early self-perceptions may have an enduring impact on a young person's mental well-being. Further, gaining insight into how the self-perceptions of children with intellectual disabilities develop during childhood may help to inform interventions designed to target the development of positive self-perceptions in children with intellectual disabilities. This thesis will focus on children with Down syndrome. Down syndrome is a chromosomal disorder and one of the most common causes of intellectual disability (Carr, 1995). People with Down syndrome have distinctive facial features, which make them immediately identifiable to others and may mean that people with Down syndrome identify themselves as different from others. The key questions addressed by the present research are: Are children with Down syndrome aware of Down syndrome and do they hold particular feelings about it? The present study was conceptualised as an exploration of children's rudimentary awareness of their disability and the social stigma attached to it. In order to explore children's perceptions, a mixed method approach was chosen. The quantitative component of the study developed pictorial methods to investigate the awareness and views children with Down syndrome hold of Down syndrome. Children completed three experimental 'tasks' that involved colour illustrations and photographs of unfamiliar children, some of which depicted children with Down syndrome and some in which children had no visible disability. Twenty-eight children with Down syndrome took part. There were two age groups; a younger group aged 8 to 12 years old (n= 10) and an older group aged 13 to 17 years old (n=18). The purpose of the two age groups was to explore potential differences in awareness shown by participants with different amounts of social experience. A comparison group of children with no disability allowed the researcher to investigate whether having Down syndrome led to differences in task performance. However, since children with Down syndrome have at least some degree of intellectual impairment, it was necessary to control for cognitive development and age separately. A cognitive ability control group enabled the researcher to ensure, as far as possible, that any differences in task performance that did occur could not be attributed to differences in participants' cognitive ability. The chronological age control group was used to help ensure that potential influence of social experience and learning, acquired with age, were also controlled for. Therefore, two groups of non-disabled participants were recruited; one group were the same chronological ages as participants with Down syndrome and the other were younger in chronological age, in the hope that their verbal ability would match that of participants with Down syndrome. However, despite their younger age, the non-disabled children scored consistently higher than participants with Down syndrome on the measure of verbal ability. Consequently, a verbal ability control group was unfortunately not achieved. Instead, the non-disabled participants were split into three age groups. The first group were younger in age and their verbal ability was closer to that of participants with Down syndrome (n=14). Although not matched on verbal ability, they were still at an earlier developmental stage and served a useful comparison group in this respect. The second group were aged 8 to 12 years old (n= 27) and the third group aged 13 to 17 years (n= 26). These groups served as chronological age-matched controls. The proportion of males and females in the Down syndrome and non-disabled groups were roughly equal. For the qualitative phase of the study, the researcher interviewed a subsample of the children's mothers' to examine what they thought about their child's understanding of Down syndrome and the social stigma attached to it. Ten mothers of children with Down syndrome took part in 1:1 semi-structured interviews. The transcripts were analysed using Interpretative Phenomenological Analysis. The responses of children with Down syndrome on the picture tasks indicated that they discriminated between the photographs of children with and without Down syndrome, they preferred to share social activities with the photographed children with no disability, they identified themselves as similar to the photographs of non-disabled children and they had less positive views about the photographed children with Down syndrome than those with no disability. Participants with no disability also demonstrated a similar bias in favour of non-disabled children during the tasks. Both participants with Down syndrome and non-disabled participants had positive views of themselves, although those with Down syndrome were slightly less positive about themselves than their non-disabled peers. The key finding from the experimental studies was the bias shown by all children in favour of photographs of children with no disability. A contrasting picture emerged from the interviews with mothers. They expressed deep concerns regarding their child's growing distance from non-disabled peers as they grew older. Nevertheless, the mothers believed their children were oblivious to their disability or, at most, were aware of it but viewed it as inconsequential. Mothers reported waiting for their child to take the lead with regards discussing Down syndrome but most reported that their children rarely asked questions related to their disability and, as a result, it was rarely a topic of conversation. A sense of responsibility to talk to their children about their disability was accompanied by deep anxiety over what was best for their children regarding when and how to tell them about Down syndrome. This research has highlighted that children with Down syndrome may be more aware of their disability and how Down syndrome is viewed socially than has been appreciated. It underscores the importance of giving children with communication difficulties a way of expressing their views. Future research should investigate the development of children's self-perceptions in relation to disability and inform ways of investigating children's growing awareness disability and related social attitudes. Such research could have an important role to play in fostering more positive ways of thinking about Down syndrome and equip them to deal with social stigma.

Background: People with intellectual disabilities (ID) may respond differently to social stressors due to differences in social conditioning and acquisition of skills. The present study examined whether social worries are more salient for young people ID than their non disabled peers, and whether there are differences in their responses to socially stressful situations. Method: Forty-one participants aged 16 to 22 took part in this study; 20 typically developing young adults and 21 with mild ID were recruited through local further education colleges. The groups participated in an open-ended ‘worry’ interview where they described their worries and rated them in terms of salience. They were then asked how they would cope in a series of 6 ‘social threat’ scenarios, using pictorial vignette stimuli. Responses for worries and coping were content analysed and categorised. Results: It was found that there were some differences between the groups in terms of content of worries reported, with the ID group reporting more worries about maintaining friendships and being bullied, whereas the non-ID group worried more about future aspirations and gaining independence. In terms of coping styles, the control group endorsed more sophisticated responses involving management of social and emotional presentation, but overall coping between the groups was broadly similar. Finally, both groups reported a high rate of ‘emotion-focussed’ responding in response to situations involving risk of social rejection, and this appears to reflect that these situations may be particularly stressful for both groups. Discussion/Implications: This study contributes to the literature on transition and social coping for those with ID, and in particular adds weight to the idea that young adults with ID have a different profile of worries at this life stage, but this does not appear to impair social coping, and those with ID possess a variety of strategies to utilise in situations of social stress, although these strategies may be less sophisticated at times than non-disabled peers.

Background: Young people who have intellectual disabilities (ID) or Autistic Spectrum Disorders (ASD) may experience stigma which can lead to them developing negative views about themselves. However, it has been shown that individuals with ID can mediate the impact of stigma through the comparisons they make with other people. People with ASD might have difficulty making these “social comparisons” because of their social cognitive difficulties. The current study explores whether a group of young people with ASD who do not have an ID or borderline/mild ID, recognise and report experiences of stigma similarly, whether they have similar levels of self-esteem, and whether individuals with ASD make social comparisons in a similar way to individuals with borderline/mild ID. Method: A group of young people with ASD, without learning disability, and a group with borderline/mild ID were recruited. Measures of stigma, self-esteem and social comparison were completed with participants. The social comparison measure was completed in relation to a person described as having a developmental disability and a typically developing individual. A subsample of participants in each group were asked to provide more detailed examples of the types of stigma they experienced to confirm that their reported experiences accurately reflected experiencing stigma. Results: Participants in the ASD group reported more experiences of being made fun of, whereas those in the borderline/mild ID group reported more experiences of being treated differently to their peers. The specific examples of stigma experiences were similar between the groups. Despite experiencing stigma, the self-esteem scores of both groups were positive. The social comparisons that both groups made in relation to developmentally disabled and typically developing peers were also positive. However the ASD group compared themselves significantly less positively to a typically developing peer than to a developmentally disabled peer. Conclusions: Young people with ASD were aware of facing stigma and compared themselves positively to individuals with intellectual and social difficulties, and less positively to typically developing individuals. The study demonstrates that individuals with ASD are able to understand situations and to make comparisons that appear to require a degree of social understanding. It remains uncertain whether making positive social comparisons helped participants to manage the impact of stigma, therefore this is an area that requires further investigation.

Depression is one of the leading causes of disability worldwide. Currently available treatment methods are not always effective in improving depression. There is thus a pressing need for the development of novel treatment methods. Neurofeedback training can potentially alleviate symptoms of depression. By providing depressed patients with feedback about the ongoing processes in their brain via functional magnetic resonance imaging (fMRI), patients can be trained to increase the activation in positive emotion processing areas by engaging in positive imagery. The advantages of this method are that it is non-invasive, offers an individually tailored approach without any side-effects and has the capability to target the neurobiological and cognitive pathways putatively mediating depression. The main aim of this thesis was to elaborate on pilot findings that fMRI-neurofeedback has potential as an add-on treatment tool for depression (Linden et al., 2012). In doing so, this thesis does not focus on confirming that fMRI-neurofeedback can improve symptoms of depression as the dataset employed here is part of a larger dataset of a currently still running clinical trial. Instead this work investigated the feasibility of a control group receiving feedback from a scene processing area and assessed whether fMRI-neurofeedback can indeed affect emotion processing areas that function abnormally in depression and enhance perceived self-efficacy. Sixteen moderately to severely depressed patients took part in a course of five neurofeedback training sessions in which all patients learned to up-regulate the activation in their individually localised target areas. The patients that had received feedback from a positive emotion area influenced the activity in a wider emotion regulation network than just their target area. Additionally, the acquisition of self-regulation skills significantly improved scores on a self-efficacy scale. These findings confirmed the ability of neurofeedback to target biological and cognitive pathways putatively mediating depression.

The overall aim of this thesis is to use the distinctive “spectrum” approach uniquely offered by the Diagnostic Interview for Social and Communication Disorders (DISCO) to explore the different descriptions of Autism Spectrum Disorder across four parts of the thesis. Part 1 introduces the concept of an “autism spectrum” and evaluates how this is continually developing. In Part 2, the focus is on the associated behaviours of ASD, that is, the behaviours not used to make a diagnosis. Sensory behaviours were found to be related to the core features of ASD, to maladaptive behaviours and were found to mediate the relationship between maladaptive behaviours and the core features of ASD, implicating sensory behaviours as having a particularly influential role in the behavioural manifestation of ASD. Further work addressed the lack of research on adults and found high-functioning adults with ASD reported significantly more sensory behaviours than IQ matched typically developing adults. Part 3 explored the measurement characteristics of two definitions of ASD: Wing and Gould (1979) and the new Diagnostic and Statistical Manual for Mental Disorders (DSM-5). A new diagnostic algorithm for DSM-5 criteria using DISCO data was designed and tested. Results showed that when the DSM-5 behaviours were mapped accurately onto a tool that is capable of measuring the spectrum, the DSM-5 criteria were found to have both good sensitivity and specificity. An advantage of the DISCO is the range of behaviours included. Comparison with Wing and Gould’s measure revealed a strong overlap in spectrum concepts and one single element “quality of social interaction” had excellent diagnostic accuracy alone. Finally, in Part 4 the findings from Part 2 and 3 are brought together and discussed and a revised definition of the “autism spectrum” is proposed with regards to a continuum of reciprocal social interaction, which proposes that the pattern of behaviours seen in ASD need to be considered in combination.

There is a growing professional concern regarding the existence of pro eating disorder (pro-ED) websites. Previous research investigating the impact of pro-ED websites has comprised analyses of website content and experimental exposure of mock pro-ED content with participants from non-clinical populations. The few studies involving the assessment of pro-ED website use in individuals with eating disorders have predominantly used online survey methodology. The findings from these studies suggest that pro-ED websites may have a detrimental impact on emotional and physical wellbeing. The present study sought to explore the function and impact of pro-ED websites in a clinical sample of individuals in treatment for an eating disorder. Participants were recruited through tier two community mental health teams and tier three specialist eating disorder services within two NHS Health Boards in South Wales. Individual face to face interviews were conducted with seven adult females receiving treatment for an eating disorder who had disclosed historic or current use of pro-ED websites. Constructivist Grounded Theory was used to analyse the data. Five key themes were identified within the interview transcripts: fear, cognitive dissonance, social comparisons, shame, and pro-ED website maintaining eating disordered behaviour. Pro-ED websites were often used to reduce a sense of social isolation, fuelled by stigma and shame associated with the eating disorder and use of pro-ED websites. Individuals experienced cognitive dissonance regarding their use of pro-ED websites, and the websites were often used to protect themselves from pressures to recover. The pro-ED websites appeared to offer a sense of support, validation and reassurance, whilst simultaneously reinforcing and maintaining eating disordered behaviour. Websites were often used to motivate food restriction, and were at times used as a method of punishment when individuals experienced self-criticism. The findings are discussed in relation to implications for eating disorder treatment services and recommendations for future research are outlined.

This thesis explores the effects of dietary probiotic administration in anxiety-like behaviour and cognitive functioning. Desbonnet et al (2008) reported degradation of serotonin in the frontal cortex following dietary probiotic administration implicating cognition and anxiety-like behaviour. Therefore, the effects of direct serotonin manipulation on behaviour were examined in parallel to probiotic treatment. Identification of a task reliant on both frontal lobe and serotonergic functioning lead to the use of the probabilistic reversal learning task. Probiotic treatment did not produce effects on this task. Exploration of the effect of probiotic treatment on a watermaze reversal learning paradigm, known to be reliant on frontal lobe and hippocampal functioning indicated improvements with probiotic treatment. Further examination of this improvement in memory was explored in a novel object discrimination task and found to be significantly improved following probiotic treatment. These results produce clear indication the probiotic treatment improves aspects of learning and memory. The effects of dietary probiotics on anxiety-like behaviour were also explored. The results from the behavioural data indicated that these tests did not assess the same facet of emotional behaviour therefore conclusions could not be drawn on the effects of probiotic on anxiety-like behaviour. Examinations of the effects of probiotics at a cellular level were conducted through the use of H1 nuclear magnetic resonance spectroscopy. Results from this illustrate distinct alterations in the metabolite profile following probiotic treatment. The finding from this study provide a new rational for the further exploration of the effects of probiotic treatment on behaviour and cognition.

Huntington’s disease (HD) is a neurodegenerative disease caused by a mutation in the huntingtin gene (HTT). The extended CAG repeat ultimately leads to loss of medium spiny neurons (MSNs) in the striatum of the HD brain. Cell replacement therapy using primary human fetal tissue as a source of “genuine” MSNs has shown ‘proof of principle’ as a strategy to treat this genetically inherited disease1. However, renewable cell sources need to be identified to overcome the ethical and logistical issues that are associated with using human fetuses. Here we attempted to generate iPS cells by introducing reprogramming factors using the piggyBac Transposon2 transduction system in human fetal fibroblasts and fetal neural stem cells. We wish to test the hypothesis that these cells are more easily reprogrammable and/or are more readily directed towards an MSN phenotype. The established iPS cell lines were similar to human embryonic stem (ES) cells in terms of their morphology, surface antigen, and proliferation. These iPS cells lines have been successfully manipulated to differentiate into MSNs in culture according to their expression of standard molecular markers of premature and mature MSNs - Ctip2 and Darrp32. Differentiation following transplantation into the quinolinic acid (QA) lesion model showed that grafts of these striatal progenitors derived from human fetal iPS cells could differentiate into neural progenitors according to expression of human nuclei marker (HuNu) and nestin.

Background: Antisocial personality is characterised by impulsive behaviour and a pervasive disregard for the rights of others. Its consequences are often debilitating and its presentation poses considerable treatment challenges. While it may be associated with a range of neuropsychological deficits, the literature is often contradictory and no research has examined their effect on treatment. Method: A systematic review of the neuropsychological literature on male adults with antisocial personality was conducted to facilitate generation of hypotheses. Pooled evidence from 132 studies suggested robust cognitive deficits in motor regulation, affect recognition, and concept formation. Findings were less consistent for other functions and differences between operationalisations of the antisocial personality were present. To further investigate the neurocognitive deficits and examine their effect on treatment, the Cambridge Neuropsychological Assessment Battery (CANTAB) was administered on 102 adult male offenders (divided into those with antisocial vs. other personality disorders) and on 20 healthy controls in a between-subjects design. Two operationalisations were examined in parallel for the first time: Antisocial Personality Disorder (ASPD) and psychopathy. Progress in treatment was measured using a two-part, standardised instrument – the Progress Rating Schedule (PRS) – developed systematically via thematic analysis as part of the project. Results: ASPD demonstrated impairments in executive, memory, attentional, and visual processing functions while psychopathy showed primarily executive but overall milder deficits. Impairments in motor regulation, set-shifting, working memory, and visual perception appeared present in the antisocial personality (ASPD and psychopathy) but not offenders with other personality disorders. Regarding progress in treatment, the PRS showed good reliability (intra-class correlations: 0.63-0.92; internal consistency: 0.77-0.87) and concurrent and predictive validity. However, cognitive difficulties predicted outcomes only to a limited extent. In ASPD, fronto-temporal deficits predicted poorer progress through the forensic pathway. However, higher risk-taking (Cambridge Gambling Task) predicted better outcomes while intellectual functioning and presence of psychopathy mediated some effects. In psychopathy, only visual short-term memory and planning predicted progress; impairments in the former predicted slower progress but there were inconsistencies for the latter. Conclusions: A range of neuropsychological deficits appeared to characterise the antisocial personality and some may have adverse effects on progress in treatment. Further research is required in other, larger samples and cognitive functions not included in the CANTAB to confirm and extend these findings.