Adults with Attention-Deficit Hyperactivity Disorder (ADHD) frequently report emotional lability (EL: irritable moods with volatile and changeable emotions). Little is known about the clinical and behavioural features, or neurobiological correlates of EL in ADHD. The current thesis takes an integrative approach, using a diversity of methodologies to characterise EL, and examine the nature of its association with ADHD. All analyses are based on data from the MIRIAD project, a case-control study of 88 adult males: 47 controls, and 41 with ADHD without comorbidity, medication or current substance abuse. The study incorporated reassessment after treatment with methylphenidate in ADHD participants, with matched follow-up for controls. The first part of this thesis examined the clinical and behavioural features of EL using self-report measures and ambulatory monitoring. Results indicated significantly elevated EL in adults with ADHD, characterized by higher intensity and instability of negative emotions. Enhanced EL was not accounted for by antisocial behaviour, subthreshold comorbid symptomatology, and adverse life events. ADHD symptoms and EL were moderately correlated, and EL independently predicted a host of daily life impairments. The second part of this thesis focused on identifying aetiological factors which may underpin both EL and ADHD, by exploring cognitive and neurophysiological deficits associated with ADHD and self-reported EL, and examining shared treatment response. Swift emotional changes were predicted by within-subject variability in reaction time, whilst EL characterized by negative emotions was associated with behavioural and neurophysiological indices of inhibitory function. Although ADHD symptoms and EL correlated moderately in their treatment response, treatment response of cognitive measures and EL were not correlated. The research presented here has implications for the identification and treatment of ADHD in adulthood in the context of elevated EL and mood symptoms. Results from cognitive and neurophysiological investigations present some promising avenues for further examining shared neurobiology of EL and ADHD.

This thesis takes a critical analytic approach to contemporary discourses of anorexia. Unlike much feminist literature on eating disorders, its emphasis is metatheoretical: rather than taking the anorexic body itself as object of enquiry, the thesis focuses on the effects of theory about anorexia. It investigates the underlying structure of dominant discourses about anorexia and, using a feminist genealogical methodology, contextualises those discourses within broader feminist theoretical debates and within historical trends in thinking 'feminine disorders'. In particular, the thesis seeks to account for the absence in contemporary theory of an engagement with how anorexia feels. It suggests that feminist cultural theorists' arguments about anorexia as a metaphor for the condition of Western women, and feminist corporeal theorists' readings of anorexia as a synecdoche for gender oppression, privilege the visual body at the expense of the affective and sentient aspects of embodiment. Moreover, the frequent feminist argument that anorexia demonstrates the harm done by thin-ideal media images indicates the extent to which much existing feminist theory reproduces, rather than surpasses, a notion of anorexics as pathological and suggestible. Building on this analysis of discursive effects, the thesis suggests some new ways of thinking existing knowledges about anorexia. It reconceptualises anorexia as a form of melancholia engendered by specific, often traumatic, forms of touch (in both physical and affective senses). Through a reflexive affective dialogic reading practice, it engages with a number of anorexic autobiographies, exploring the effects and limitations for anorexic subjects of the imperative to represent one's life truthfully, and the narrative strategies through which anorexic autobiographers have circumvented truth-judgements. By foregrounding the significance of touch to both anorexic body and narrative, the thesis reframes anorexia in intersubjective terms and recentralises family dynamics as key to many anorexics' conceptions of self.

Autism spectrum disorders (ASD) are characterised by social-communication difficulties and non-social symptoms such as restricted and repetitive behaviours and interests. ASD characteristics can be investigated at the subclinical trait level within the general population, and these quantitative autistic traits have been shown to have a smooth distribution. Adolescence is an important developmental stage, particularly for the emergence of internalising problems. However, few studies to date have investigated the causes of co-occurring autistic traits and internalising traits during adolescence. The aim of this thesis is to explore the aetiological causes of this trait association between the ages of 12 to 16 years using a quantitative genetic approach. This thesis employs a classic twin design and the sample came from the Twins Early Development Study (TEDS). The causes of the association between autistic and internalising traits in early adolescence are the first focus of this thesis. The analyses in Chapter 4 explore this aetiological association at ages 12-14 years, revealing a moderate phenotypic trait association and at the aetiological level moderate genetic overlap, substantial shared environmental and modest nonshared environmental overlap. Teasing apart these associations further, Chapter 5 identifies specific autistic-like behaviours by means of factor analysis. Relating these factor-derived autistic trait subdomains to the internalising trait measure demonstrated distinguishable patterns of phenotypic and aetiological associations. A factor named autistic-like ‘Social Unease’ showed the most phenotypic and genetic overlap with internalising traits. Secondly, this thesis investigates in Chapter 6 the role of childhood nonshared environment on internalising and autistic traits in early adolescence using the monozygotic twin differences design. Analyses showed that birth weight, childhood hyperactivity and peer problems played a role, via the nonshared environment, in influencing individual differences in internalising and autistic traits in early adolescence. Finally, Chapter 7 presents findings on later adolescence, at age 16 years, exploring the association of autistic traits with anxiety traits and depression traits separately and drawing on both parent and self ratings. The implications of these findings, their limitations and their contribution to the current literature are considered in the Discussion (Chapter 8).

Overview This volume is separated into three parts: • Part 1: Literature review. A systematic review and meta-analysis of twelve randomised controlled trials that examined the efficacy of psychological treatment for vaginal pain. The aim was to understand whether efficacy of treatment differed for vaginal pain defined as medical or psychiatric in aetiology. Differences and similarities in efficacy were examined on outcomes of pain and sexual function. Effectiveness of psychological treatment was found to be comparable regardless of aetiology, indicating that this distinction may not be helpful for informing treatment decisions. • Part 2: Empirical paper. A mixed methods study evaluated a new computerised programme for six women with vaginismus. Change in pain-related fear, penetration behaviour and pain intensity was quantitatively assessed. Interviews were used to qualitatively explore acceptability and change. Pain-related fear and pain intensity reduced over the course of the programme; successful penetration increased. The programme was experienced as convenient, gradual, and supportive, with moments of frustration at progress. The programme also had a positive influence on self-awareness, confidence, normalisation, and approach behaviours, with exposure attributed as the most difficult but important aspect of change. • Part 3: Critical appraisal. An appraisal of methodology used in the empirical study, discussing the potential biases encountered with research allegiance.

Fear, helplessness and horror are the emotions traditionally linked with posttraumatic stress disorder (PTSD) and are central to the current diagnostic criteria. However recent research suggests that a range of other emotions may also play a role in PTSD, and researchers have specifically identified a subgroup of people whose severity of PTSD was linked to the severity of shame they experienced. Recently researchers have been interested in the role individuals' inner dialogues have on the development and maintenance of shame. Specifically it has been suggested that shame is linked to self-critical inner dialogues and an inability to be caring and compassionate towards the self. In this paper these ideas are explored in relation to PTSD. It is suggested that self- criticism and a lack of a caring and compassionate part of the self can lead individuals who have suffered a trauma to experience high levels of shame and as a consequence feel as if their psychological integrity is under threat. Continued self-critical attacks maintain a sense of ongoing current threat, which as specified in Ehlers and Clark's (2000) cognitive model of PTSD is central to the creation and maintenance of PTSD. It is suggested that treatment interventions that focus on the development of a caring and compassionate part of the self are likely to prove a beneficial adjunct to traditional exposure based treatments for individuals who have PTSD associated with high levels of shame.

The success of epilepsy surgery critically depends on precise identification of the epileptogenic zone, which is a costly process due to extensive diagnostic testing. Localisation of epileptogenic areas for surgical resection is still an imperfect process and long term seizure freedom is seen in fewer than half of the patients operated. These factors have directed efforts towards finding alternative biomarkers of epileptogenicity. High Frequency Oscillations (HFO) and abnormal responses to Single Pulse Electrical Stimulation (SPES) in the intracranial EEG have been proposed to be indicative of the seizure onset zone (SOZ). Removal of areas positive for these biomarkers has been linked to a good post-surgical outcome. Moreover, magnetoencephalography (MEG), which is known to provide additional localising information, offers the appealing possibility of detecting epileptic activity non-invasively. This work describes the analysis of HFO and SPES in patients with refractory epilepsy undergoing presurgical evaluation. The relationship between both of these methods and the SOZ, lesion and surgical outcome was evaluated in an attempt to determine whether they could offer additional information during the presurgical assessment of epilepsy. In addition, the use of MEG for potentially detecting pathological high frequency activity non-invasively has also been explored. The detection of HFO and abnormal SPES was not as reliable as previously described and there were significant pitfalls in HFO detection in clinical EEG data. Unexpectedly, both HFO and abnormal SPES were detected in very few patients; in most, only one of the two could be detected, indicating that the information provided by these is complimentary. Detection of HFO with MEG was severely compromised by muscle artefact, which could lead to misinterpretation of high frequency activity recorded with MEG.

The central aim of this review was to consider whether theories developed within mainstream aggression research might also be usefully applied in the prediction of violence amongst a mentally disordered population. Current understanding of the relationship between mental illness and violence suggests that our knowledge could be advanced by consideration of factors beyond those intrinsic to diagnosis. Particular predictors identified within mainstream research, such as narcissistic personality traits, and hostile cognitive biases, offer a clear focus for future study development. Furthermore, it would seem that there is a need for mainstream research to apply its concepts to more clinically-relevant populations, such as the mentally disordered, if they are to be considered robust and generalisable theories of aggression.

In this paper I will review literature concerning shame and distinguish it from other similar emotions such as embarrassment and guilt. Shame and guilt are emotional reactions that often occur in response to transgressions, and concern perceived evaluations by others and/or the self. It has been proposed that shame and guilt have very different effects, and that guilt acts as a mediator, whereas shame acts as a barrier to the experience of empathy. Shame and guilt and their relationship to empathy will be explored, and key studies demonstrating their inter-relationships will be critically evaluated. The latter part of this review will focus on sex offenders, and will discuss the relevance of considering and incorporating an understanding of self-conscious emotions in the treatment of sex offenders. The emerging findings concerning shame, guilt and empathy will be explored in light of the fact that empathy training is a significant feature of most sex offender treatment programmes. There is a dearth of research about shame in sex offenders, and its relationship to guilt and empathy in this population, although there is much speculation and some evidence that shame is prevalent within this population. If high levels of shame hinder the experience of empathy, then for those sex offenders who may be unable to, or have great difficulty experiencing empathy due to excessive shame, empathy training as part of their treatment might render them a greater risk. Such training might have the effect of teaching individuals who lack empathy to some degree skills in acting empathically, but may not necessarily enhance the genuine experience of it. Thus, teaching empathy to some sex offenders may have the effect of improving their grooming skills as being able to feign empathy might be useful when it comes to securing victims. Attribution theory is outlined and considered in terms of the treatment of sex offenders, and the view that guilt but not shame should be encouraged when working clinically with sex offenders will be explicated against the backdrop of what is currently known about shame and guilt, and their effects on empathy.

Anterior temporal lobe resections (ATLR) provide an effective treatment option for patients with medically refractory temporal lobe epilepsy (TLE) rendering up to 70% of them seizure free. The goal of epilepsy surgery is to remove the brain areas generating the seizures without causing neuropsychological deficits such as language or memory dysfunction. Furthermore up to 60% of patients with TLE suffer from emotional disturbances following surgery. The principle aim of the work presented in this thesis was to improve presurgical evaluation of patients with TLE by using cognitive functional MRI (fMRI) to non-invasively localise brain areas that are essential for processing cognitive function such as language and memory function and emotional and social behaviour. 150 consecutive patients and 40 healthy controls were included in our experiments. Different fMRI paradigms for the evaluation of cognitive functions have been implemented on a 3 Tesla scanner. All subjects underwent language and memory fMRI and standard neuropsychological assessment; those patients who proceeded to have temporal lobe surgery were reinvestigated 4 months following ATLR. We studied the efficiency of reorganisation of language and memory function due to the underlying disease and in particular following ATLR. Amygdala fMRI was used to investigate potential implications on emotional and social outcome. A major part of the work included in this thesis has concentrated on the use of fMRI for the exploration and prediction of postoperative complications such as language and memory impairment but also emotional disturbances. When used in concert with other MR imaging modalities the results of these methods can be used to improve surgical strategies tailored to individual patients with regard to functional outcome, by virtue of definition of epileptic cerebral areas that need to be resected and eloquent areas that need to be spared.

Huntington's disease (HD) is an autosomally dominant, progressive movement disorder, caused by an expansion in the polyglutamine tract of huntingtin protein. HD is pathologically characterised by the presence of insoluble, proteinaceous neuronal intranuclear inclusions (NHs) and dystrophic neurite inclusions (DNIs) in affected neurons that can be immunostained for ubiquitin and other proteins involved in the ubiquitin-proteasome system (UPS). The UPS is a highly conserved mechanism for degradation of both normal and misfolded proteins in eukaryotic cells. This has led to suggestions that the UPS is inhibited in HD. This study utilises microscopy, biochemistry and fluorometric assays to examine the molecular composition of aggregates and the potential dysfunction of the UPS in the R6/2 mouse line, an established model of HD. The ultrastructure of aggregates is shown to be predominantly amorphous and granular in appearance and likely to be formed through the process of transglutamination. Immunohistochemical data shows that certain chaperones, ubiquitin-like proteins (UBLs) and proteins involved in the UPS localise to Nils and DNIs differentially. Fluorometric assays demonstrate that the proteasome exhibits a differential profile in R6/2 mice where both chymotrypsin-like and PGPH-like activities are markedly increased whilst trypsin-like activity is decreased relative to litter-mate control mice. Furthermore, these activity changes may be explained by alterations in proteasome regulation, levels and maturation. These results suggest that, in the R6/2 line, the proteasome is not inhibited by the presence of mutant huntingtin, rather that there are alterations of the catalytic activities of the proteasome. It appears that Nil's act not only as focal points of proteolysis, but also of proteasome biogenesis. This is consistent with, and extends, the concept of clastosomes.