Huntington’s disease (HD) is a neurodegenerative disorder characterised by an unstable polyglutamine repeat expansion within the Huntingtin gene. Although clinical diagnosis of HD relies on the manifestation of a motor phenotype, cognitive symptoms often appear prior to diagnosis. This study has characterised the motor, cognitive and electrophysiological phenotypes of the homozygous and heterozygous HdhQ111 mouse models of HD. Although the heterozygous HdhQ111 mouse is more clinically relevant to the human disorder, it has received little attention in previous studies. Assessments of the motor phenotype of the HdhQ111 mouse were inconclusive. However, HdhQ111 mice exhibited a mild motor phenotype on the rotarod, showing hyperactivity at 2 and 3 months. Subtle changes within the hippocampus are thought to underlie the cognitive abnormalities that characterise the early stages of HD. A series of recognition tasks were used to assess the episodic memory of the HdhQ111 mouse. Although these tasks had been used to assess the ability of rats to discriminate the ‘what’, ‘where’ and ‘when’ of episodic memory, this was the first time that they had been successfully utilised in mice. HdhQ111 mice showed impairments in episodic memory as early as 2 months. In mouse models, cognitive deficits are often accompanied by impairments in hippocampal synaptic plasticity, the molecular correlate of learning and memory. In agreement, HdhQ111 mice showed impairments in long-term potentiation (LTP) at 2 months. A novel, shortened version of the protocol was developed to accurately assess the changes in cognition in the small development window available. A hippocampus-dependent 24-hour novel object recognition task was also used to assess the integrity of the hippocampus. Hippocampal function in 1 month old HdhQ111 mice was not significantly different from that in wild type mice. The early cognitive deficits present in the HdhQ111 mice were progressive, with cognitive deficits spreading to include the individual components of episodic memory by 13 months. Drugs inhibiting the function of a5-GABAA receptors are known to enhance cognition and hippocampal LTP. In agreement, the LTP and cognitive deficits of the HdhQ111 mouse were rescued following treatment with the a5-GABAA receptors selective inverse agonist a5IA. Importantly, the clinically relevant heterozygous HdhQ111 mice exhibited an identical phenotype to homozygous HdhQ111 mice indicating that, reminiscent of the human disorder, only one copy of the mutant gene is necessary to produce abnormalities associated with the disorder, further supporting the validity of the HdhQ111 mouse as a clinically relevant model of HD. Collectively, this thesis provides evidence that a5-GABAA receptors antagonists have the potential to improve cognitive function in HD.

Introduction: Many people believe that obesity is caused by an addiction to food. However, within the scientific community, there is ongoing debate surrounding the validity of the food addiction concept, and an operational definition of food addiction is yet to be established. An aim of the current thesis was to identify behaviours and cognitions which characterise addictive patterns of eating. To do so, Chapters 2-4 explored the characteristics of individuals who perceive themselves to be addicted to food (i.e. self-perceived food addicts). Based on these findings, Chapter 5 presents the development of a novel assessment tool for addictive-like eating. A second aim of the thesis was to explore food addiction beliefs from a psychosocial perspective. Specifically, Chapter 6 examined the consequences of food addiction beliefs on subsequent eating, and Chapter 7 explored whether the concept of food addiction may be used to alleviate eating-related guilt by implying that eating is beyond personal control. Methods: A combination of qualitative and experimental techniques were used to establish the cognitive and behavioural features of self- perceived food addiction. Chapter 2 consisted of a brief questionnaire which inductively explored beliefs about the manifestations of food addiction within the lay public. These findings were extended in Chapters 3 and 4 which experimentally tested whether self-perceived food addicts would demonstrate increased food reward and attention to high-fat food cues (using an eye-tracking paradigm), compared to those who do not perceive themselves as food addicts. Chapter 5 used exploratory and confirmatory factor analyses to develop a novel tool for the assessment of addictive eating (i.e. the Addictive Eating Behaviour Scale, AEBS). To address the second aim of the thesis, experimental techniques were used to manipulate participants’ beliefs about their levels of food addiction (Chapter 6) and feelings of eating-related guilt (Chapter 7). The effects of these beliefs on subsequent food intake (Chapter 6) and food addiction attributions (Chapter 7) were then examined. Results: Findings from Chapter 2 suggested that self-perceived food addicts find food particularly rewarding and may be particularly likely to overeat. Consistent with these findings, Chapter 3 found that self-perceived food addicts demonstrated increased desire-to-eat for a range of food, and consumed more of a high-fat food during ad libitum access, compared to self-perceived non-addicts. However, self- perceived food addicts did not show any increased attentional bias to food cues compared to non-addicts (Chapter 4). The AEBS (Chapter 5) consisted of two sub- scales: 1) unhealthy eating/low self-control, and 2) overeating/weight gain. This scale predicted variance in BMI beyond that accounted for by an existing measure of food addiction. With regard to the second aim of the thesis, Chapter 6 found that those who were told they had high levels of ‘food addiction’ consumed fewer calories compared to those who were told they had ‘low’ or ‘average’ food addiction. This was mediated by increased dietary concern and a reduction in the amount of time spent tasting high-fat foods. Finally, Chapter 7 found no effect of manipulating eating-related guilt on food addiction beliefs; however, across the whole sample, higher levels of guilt correlated with an increased tendency to attribute eating to the foods’ addictiveness. Conclusions:Overall, these findings suggest that self-perceived food addiction is characterised by several core behaviours, and that perceiving oneself to be a food addict may be helpful for those attempting to reduce their intake of certain foods, in the short-term at least. Future research should establish whether the AEBS captures food reward and calorie intake beyond that accounted for by established measures of aberrant dietary behaviour. Research should also examine the effects of food addiction beliefs on longer-term patterns of eating.

This thesis aims to enhance understanding of the lived experience of autism from individuals’ perspectives, voices typically marginalised within research, just as their needs have been marginalised within society. The research comprises: a systematic review and an empirical study. The literature review synthesises and critically evaluates 14 qualitative studies on the experience of autism in adulthood. Six themes representing core features of experience were identified: identity and self-perception; interpersonal relationships; sensory experiences; dating and sexual experiences; institutional experiences; employment. The findings highlight the balance required between targeting remediation of autism-related difficulties, and efforts to make society, its services, public spaces, and institutions more autism-aware and inclusive. Future research directions are highlighted including a need for qualitative research exploration of sexuality, gender identity and related support needs. In response to this review and the small but growing body of research describing the co-occurrence of gender dysphoria in people with autism, a qualitative study was undertaken investigating the impact of autism on the experience of gender dysphoria. A theoretical framework was developed of common processes involved in understanding and addressing GD, the influence of autism and the social environment. The overall experience is captured in the core category conflict versus congruence. Individuals achieve greater personal congruence and wellbeing upon social and physical transition. However, conflicts remain related to fear of hostility and an enduring sense of difference. Services facilitating increased social support and proactively addressing gender and sexual issues are recommended.

The research reported in this thesis examined social anxiety in people with visible skin conditions to identify potential targets for intervention. Mindfulness refers to the tendency to pay attention to the present and cultivates a non-judgmental attitude towards experiences. Disengaging from negative patterns of thinking by paying attention to the present, could target rumination which maintains social anxiety. The findings of Study 1, an interpretative phenomenological analysis (N=10) indicated that social anxiety in people living with visible skin conditions arises as a result of an interaction between negative self-appraisals, fear of negative evaluation and previous reactions of others. Targeting this evaluative process using mindfulness techniques could be beneficial in reducing social anxiety; therefore, Study 2 examined the relationship between mindfulness and psychosocial distress in people with visible skin conditions (N=120). Mindfulness explained 41% of the variance in social anxiety, after controlling for subjective severity. These findings suggest that increasing mindfulness, particularly awareness, and non-judgment of inner experience could reduce social anxiety. To examine the potential of mindfulness interventions to reduce social anxiety, a systematic review was conducted. Findings highlighted that mindfulness is effective in reducing social anxiety. Potential mechanisms for the effects of mindfulness include reduced reactivity to negative self-referential information and increased attentional control. Study 3 tested the effectiveness of Mindfulness Based Cognitive Therapy (MBCT) for social anxiety in people with visible skin conditions. A multiple baseline single case series was used to examine individual change profiles over time. Reliable and/or clinically significant reductions in social anxiety and at least one other area of psychosocial distress were reported by treatment completers (N = 7). The findings suggest that MBCT is a promising intervention for social anxiety in dermatology patients, and further research is warranted. Feasibility studies may provide important information regarding recruitment and attrition when considering randomised control trials.

First, a systematic literature review assessed the efficacy of third-wave interventions to treat individuals who have been diagnosed with an eating disorder. Twenty-three studies which cover five forms of intervention were considered - Acceptance and Commitment Therapy, Compassion Focussed Therapy, Dialectical Behaviour Therapy, Mindfulness-Based Interventions, and Schema Therapy. At present, this field of research is in its infancy, as is reflected in the quantity and quality of the studies available for this review. Dialectical Behaviour Therapy appears to be the most robust third-wave intervention in this field. A lack of meaningful comparisons means that further research is required to compare third-wave interventions with other evidenced-based psychological interventions. Second, the empirical report developed an eating-pathology-specific measure of interpersonal problems, intended to have greater clinical utility for eating pathology than a generic interpersonal problems measure. A large community sample of participants completed online psychometric measures including a novel eating-specific interpersonal problems questionnaire - the Interpersonal Problems in Eating Disorders scale (IR-ED). Participants also completed a generic measure of interpersonal problems and measures of depression, anxiety, social anxiety and eating pathology. The IR-ED has strong psychometric validity. In comparison to the generic measure of interpersonal problems, the final 15-item version of the IR-ED shows similar associations with depression and anxiety and a superior ability to detect and predict eating pathology. The two components of this thesis expand upon traditional approaches of psychological intervention for people who experience eating pathology by considering the context within which individuals cognitions occur.

Literature review. The current systematic review examined the relationship between sensory and repetitive behaviours in individuals with autism. Fifteen studies were selected according to relevant search terms and inclusion/exclusion criteria. Although results showed significant correlations between sensory and repetitive behaviours, there was much variability. The relationship was also likely to be artificially inflated due to the weaknesses of the measures used to assess these constructs. Methodological weaknesses of included studies are discussed as well as clinical implications and recommendations for future research. Research Report. The research report attempted to reconcile two competing (neuronal inhibition verses excitation) theories of autism, by examining the impact of epilepsy (a disorder caused by increased excitation) on visual discrimination abilities (whereby superior orientation discrimination abilities are thought to be an index of increased inhibition). In line with the inhibition theory it was hypothesised that the ASD group would show significantly better orientation discrimination abilities, whereas the epilepsy group would perform significantly poorer. Orientation discrimination abilities were compared in three groups of children; those with ASD, epilepsy or neuro-typical controls. Results found no superior discrimination abilities in the ASD group, which may suggest that visual discrimination abilities are not a reliable marker for increased inhibition. However, the epilepsy group showed significantly poorer discrimination abilities compared to neuro-typical controls. This would be expected by both inhibition and excitation theories. Methodological weaknesses, theoretical implications and suggestions for further work are considered.

A systematic review identified 34 studies allowing direct comparisons of depression in patients with psychogenic non-epileptic seizures (PNES) and patients with epilepsy. A meta-analysis found patients with PNES self-reported significantly higher levels of depression than patients with epilepsy. However, group differences in rates of clinical depression were less pronounced, suggesting either under-diagnosis or over self-reporting of depression in patients with PNES. Patients with PNES reported more physical symptoms of depression than those with epilepsy. Whilst depression had a similar effect on health-related quality of life in both patient groups, it was more closely associated with seizure-related variables in patients with epilepsy and interpersonal factors in patients with PNES. A core cognitive feature of depression is repetitive negative thinking, which is a common element of many psychiatric disorders. To explore repetitive negative thinking and catastrophising of seizures in patients with PNES and patients with epilepsy, 59 participants completed a series of self-report questionnaires and 29 also completed a masked and unmasked emotional Stroop task. Patients with PNES self-reported higher levels of repetitive negative thinking, catastrophising of seizures, anxiety and depression than patients with epilepsy; although no significant group differences were found on either emotional Stroop task. This suggested a difference between self-reported catastrophising of seizures and implicit seizure phobia. A possible link between repetitive negative thinking and emotional avoidance could account for these findings. The elevated levels of repetitive negative thinking in patients with PNES suggest this could be a target for psychological intervention.

The question of whether psychopaths are morally responsible is a difficult one for philosophers and non-philosophers alike. In comparison to some other forms of mental illness, it is difficult to locate intuitions concerning what our attitudes to psychopaths should be and how they should be treated. This is because, unlike people with some other forms of mental illness, psychopaths (qua psychopaths) do not appear to be mistaken about the facts bearing on their choices, but they do appear to lack understanding of the world in an important way. Working within an understanding of moral responsibility as consisting in responsiveness to reasons, I argue that psychopaths lack responsiveness to certain kinds of reasons and are therefore not morally responsible for failing to act on reasons of these kinds. Based on a review of the empirical evidence, I conclude that psychopaths experience deficiencies of emotional engagement and of empathy, which are the result of events that are not under their control. I argue that these deficiencies lead ‘hardcore’ psychopaths (those at the high end of the scale for the deficiencies in question) to fail to develop the capacity to recognise entities other than themselves as sources of value, and thus to recognise that the rights, interests and concerns of others provide reasons which bear on their choices. These psychopaths are therefore not morally responsible for failing to act on such reasons. Nonetheless, I argue that these reasons apply to psychopaths’ choices in a way that they do not apply, for example, to the choices of non-human animals. Implications of these conclusions include 1) that some reactive attitudes, such as resentment or hurt feelings, are inappropriate when directed at psychopaths, and 2) that some justifications for punishment are unavailable in the case of psychopaths.

Rumination has classically been associated with depressive symptoms and is often used as a clinical indicator for depression; however, a re-evaluation has recently suggested rumination may comprise of two sub-components: adaptive reflection, and maladaptive brooding. A separate line of enquiry has used evolutionary thinking to suggest that rumination is an adaptive process which facilitates problem solving. To date, there is little in the way of empirical support for these claims, nor have there been investigations into how the reflection/brooding dichotomy may fit into the adaptive framework. Moreover, no comment has been made with regard to the mechanisms through which rumination may influence problem solving. Four experiments sought to address these issues and better understand rumination in non-clinical populations. The results from study one indicate that reflection and brooding are both associated with improved problem solving in social-type and risk-reward problem solving, but not in abstract problem solving. In study two, reflective rumination was found to be positively associated with working memory capacity, whereas brooding and analytical ruminations were associated with slowed responses in a Posner attention task and stop signal reaction time task respectively. Study three explored the novel observation that brooding was useful in risk-reward scenarios, with results indicating that the availability of risk information did not moderate the effects of brooding. Finally, study four explores whether differences exist between trait and state rumination and if these differences may account for inconsistencies between studies. From these results, it is clear that rumination can no longer be treated as a unitary construct. More critically, the notion of brooding as a maladaptive force must be reconsidered by the wider literature, and it is advised that future research consider the relative balance between reflection and brooding in their samples.

This thesis aimed to investigate possible cognitive underpinnings of sayant skills in autism spectrum disorders (ASD). Since savant skills are overrepresented amongq individuals with ASD, several cognitive functions thought to be intact or enhanced in these individuals were hypothesised to contribute to savant skill development. In particular, central coherence, implicit learning, perceptual functioning, and infonnation processing speed were assessed in a group of nonsavant children with ASD (n=28), age, IQ, and gender (group-wise) matched controls (n=28), a group of typicall~' developing children (n=64), and finally a series of four savants with ~~SD. Consistent with previous reports, weak central coherence, Intact implicit learning and infonnation processing speed, and particularly good ability to reproduce a time window were shown in both savant and nons avant individuals with ASD. Savants also showed indications of good memory and idiosyncratic sensory functioning. As predicted, there was evidence that infonnation processing speed was IQ independent in ASD whereas it was significantly related to IQ in both comparison groups. There was also preliminary indication, via correlations and subgroup analyses, of cross modal central coherence, particularly within the ASD group. A "gateway model", in which certain cognitive functions need to be intact (or superior) in order for individuals (especially those with ASD) to develop savant skills, was proposed to account for these findings. The present findings are preliminary in nature but provide indications that certain cognitive functions more characteristic of the cognitive profile in .\SD may be necessary but insufficient for savant skill development.