Autism Spectrum Disorders (ASD) are neurodevelopmental syndromes affecting 1%-2% of all children. The aetiology of ASD is unknown, yet evidence supports a role for both genetic and non-genetic, including environmental, factors in aetiology. This thesis includes four related studies examining the role of maternal factors, and in particular maternal age, in the aetiology of ASD. Using methods of meta-analysis, national Swedish health registers, as well as a multinational cohort combining national registers from five countries this thesis examined: (a) the hypothesis that advancing maternal age is associated with ASD in the offspring ; (b) the hypothesis that maternal reproductive treatments are associated with ASD risk; and (c) the familial risk for ASD. The meta-analysis provided support for the hypothesis that advancing maternal age is associated with risk for ASD in the offspring. Risk for ASD was 1.3 fold higher (95%CI:1.2-1.4) for offspring of mothers 35 years old or older compared with mothers 25-29. The multinational cohort provided further support for the hypothesis demonstrating an independent effects of paternal and maternal age on risk for ASD. In addition, in addition to the effect of advancing age this study showed an increased risk with increasing differences in age between the spouses. Fertility treatments, overall, were not associated with risk for autism [RR=1.1; 95% 0.9-1.4]. However, in treatments for the most severe form of male infertility there was a strong association RR=4.6 (95%CI: 2.1-9.9). Our family study demonstrated that genetic factors explain half of the liability to ASD (h2=50%, 95% CI:). Factors related to maternal intrauterine environment do not seem to play a substantial role in autism aetiology. In conclusion, maternal age represents a moderate risk factor for autism. The mechanisms underlying this effect may involve both genomic and social factors, and should be rigorously examined in future studies.

Down syndrome (DS) is associated with a specific verbal short-term memory (STM) deficit. Given the strong association between verbal STM and the development of vocabulary and comprehension, it is important that this deficit is understood and addressed. The first part of this thesis sought to highlight the basis of verbal STM problems in those with DS, exploring key components of STM performance (Experiments 1, 2, 3, 4a, 4b and 4c). I also investigated effects upon item and order memory respectively (Experiments 3, 4a, 4b and 4c), using process dissociation. Individuals with DS and vocabulary matched typically developing (TD) children experienced significant serial recall improvements as a result of temporal grouping, semantic relation, visual presentation, item frequency, and pre-exposure to items. Both groups also showed evidence of phonological coding of verbal input. However, significantly poorer verbal STM performance was observed in those with DS across all comparisons with TD children, and the findings consistently indicated that this deficit reflected both item and order memory difficulties. Those with DS also displayed limitations processing the temporal context of purely verbal input, and displayed a reduced semantic relation benefit, relative to TD comparison children. These findings theoretically informed the design of a subsequent trammg experiment (Experiment 5), focussing on the use of phonological and semantic associations to support recall of items, and visuospatial support to enhance order memory. Individuals with DS experienced difficulties retrieving the correct associated items. However, vi suo spatial SUppOlt resulted in significant improvements in serial recall performance in those with DS. A follow up experiment revealed that spatial support plays a significant role at encoding (Experiment 6), but benefits appear to be bigger if a spatial component is present throughout encoding and recall (Experiment 5). This thesis shows that, whilst memory performance in DS and TD individuals is moderated by some common factors, there are distinct patterns of deficits shown in DS individuals. The findings highlight suitable areas to target in future training studies, and potential approaches to incorporate in interventions.

Antidepressant-induced adverse effects are common, occur early on in treatment and affect adherence. This thesis aims to gain a greater understanding of genetic markers involved in antidepressant-induced adverse effects. This will include: (i) clarifying the role of the most widely studied polymorphism in this area, the serotonin transporter linked polymorphic region (5-HTTLPR), on discontinuation from antidepressant treatment; (ii) improving our understanding of the adverse effects induced by two pharmacologically different antidepressants; and (iii) examining whether genetic markers can be used to guide antidepressant choice by reducing the risk of experiencing adverse effects. A systematic review and meta-analysis (total n=4309) was performed to investigate the effect of 5-HTTLPR on discontinuation from antidepressant treatment. Data from the GENPOD trial (n=601) were analysed to investigate the adverse effects induced by citalopram or reboxetine. Genetic data from GENPOD were analysed to identify genetic markers that had a differential effect on antidepressant-induced adverse effects. This involved both a genome-wide approach with an independent replication sample and a candidate gene approach. A meta-analysis of previous studies provided no evidence that 5-HTTLPR was associated with discontinuation from SSRls in Europeans. Antidepressant-induced dizziness and the total number of adverse effects were associated with discontinuation in the GENPOD trial. Reports of physical symptoms were high when patients were medication free and adverse effects reduced with time. No genetic markers differentially predicted the occurrence of antidepressant-induced adverse effects. 5-HTTLPR did not identify individuals at higher risk for discontinuation of antidepressant treatment, however larger sample sizes are required before its clinically utility can be excluded. Although adverse decreased with time they were still commonly reported throughout the trial. Distinguishing between physical symptoms of depression and adverse effects remains a challenge. At present, pharmacogenetics cannot be used to guide clinical practice in terms of the occurrence of antidepressant-induced adverse effects. The establishment of consortia collecting standardised data and conducting pooled analyses across large datasets may further research in this area.

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Anxiety disorders in children and adolescents are a common psychiatric problem. Although research and treatment has developed greatly, adolescents have been largely overlooked. Studies of normative development suggest that adolescence is a distinct phase of development. These developmental differences may account for the (albeit mixed) evidence that adolescents with anxiety disorders have significantly poorer treatment outcomes, compared to anxious children. The aim of the papers in this thesis was to develop understanding of characteristics of anxious adolescents that could be addressed through psychological treatment, relating to clinical presentation, cognitive biases and parenting behaviours. Adolescents with anxiety disorders, compared to children with anxiety disorders, were found to have more severe anxiety symptoms, more frequent primary diagnoses of social anxiety disorder, diagnoses/symptoms of mood disorders, and irregular school attendance. Parents of adolescents showed significantly lower levels of expressed anxiety, intrusiveness and warmth/engagement than parents of children. Furthermore, offspring age moderated the association between anxiety disorder status and parenting behaviours, in that parents of adolescents with anxiety disorders showed significantly higher intrusiveness and lower warmth/engagement than parents of non-anxious adolescents, but no significant differences were found between anxious and non-anxious children. The findings for adolescents were consistent with the existing literature, although with stronger effects for parental lack of warmth than other, mainly community-based, studies have found. Finally, children and adolescents with anxiety disorders showed significantly higher levels of threat interpretation and avoidant strategies than non-anxious children and adolescents. However, age significantly moderated the effect of anxiety disorder status; adolescents with anxiety disorders showed significantly higher levels of threat interpretation than non-anxious adolescents, but, again, there were no significant differences between anxious and non-anxious children. Taken together, these results underline the importance of taking age into account in order to improve understanding of the critical components of adolescent-specific treatments for anxiety disorders.

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Initially, this thesis presents an idiographic systematic review that explored how adult survivors of childhood sexual abuse experience talking therapies. The key findings suggest that although the process of healing is challenging and often viewed as an ongoing process, talking therapies can facilitate healing through developing trust, safety, relational equality and establishing interpersonal connections. Additionally, the experiential learning of choice, control, respect and being believed was essential for long-term healing, which could facilitate intrapersonal reconnection. Secondly, the findings of an empirical study are presented, which qualitatively explored how people who dissociate experience therapeutic relationships with ward based staff through interpretative phenomenological analysis. The three superordinate themes suggest that the participants faced a number of challenges. For instance, managing their dissociative experiences alongside the inconsistent relationships on the wards, the difficulties of having differing interpersonal needs at varying times and the importance of working with alters, not around them. The findings reaffirmed the importance of therapeutic relationships for the purposes of feeling safe, being able to connect to others and then the self, feeling recognised as a whole person and accepted rather than judged. The results discuss how staff can facilitate this process and the implications for ward based treatment are considered in relation to the existing literature. Thirdly, the systematic review and empirical study are reflected upon through a critical appraisal, primarily focussing on the empirical paper, which concludes the thesis. Further findings from the empirical study are presented that discuss how participants reported experiencing dissociation on wards and the impact of their experiences for therapeutic relationships. The experience of completing the study is also considered, in accordance with changing perspectives in light of the meaning making processes of the participants.

The current thesis firstly investigated the effectiveness of the IRAP as an accurate measurement of private verbal behaviours related to body weight/image dissatisfaction. Secondly, it implemented an applied study using a component from ACT and CBT in conjunction with experimental procedures to measure the believability and discomfort of target behaviours related to body image dissatisfaction and self/body-esteem. A series of pilot studies enhanced the practical application of experimental procedures and provided the textual stimuli for Experiment 1. The first experiment compared the IAT and the IRAP along with a series of explicit measures to investigate the measurement of weight related attitudes and self-esteem. These results demonstrated the IRAPs potential to measure relational responses related to the target behaviours. Experiment 2 investigated the utility of an Ideal and Perceived Body Image IRAP's as suitable measures of implicit attitudes towards target behaviours. In this experiment the Body Image IRAPs out-performed the textual IRAP employed in Experiment 1. The final study measured the effect of cognitive defusion and cognitive distraction on the frequency, the discomfort and believability of target thoughts. Specifically in relation to the effect acceptance of negative thoughts had on decreasing the believability or discomfort of negative cognitions. These findings indicated advantages for using cognitive defusion over cognitive distraction.

Empirical studies and theoretical models discussing psychological and psychosocial wellbeing following brain injury have increasingly suggested the importance of rehabilitation interventions which take into account the psychological resources of the individual, as opposed to focusing solely on cognitive or physical impairment. The first paper systematically reviewed 27 quantitative studies to identify predictors or correlates of self-esteem following acquired brain injury (ABI) in adulthood. Various psychological variables are associated with low self-esteem, including greater changes in perceived identity and self-concept, poorer adjustment and higher levels of perceived loss. Higher self-esteem appears to be related to greater physical and functional impairment. The relationship between self-esteem and cognitive impairment is unclear. Low self-esteem is also strongly related to depression and poorer psychological outcomes following ABI. The second paper describes a research project exploring social anxiety following traumatic brain injury (TBI). Despite the impact of TBI on physical, cognitive and social outcomes, no research to date has explored the role of psychological factors influencing the development of social anxiety. Hierarchical multiple regression was used to investigate demographic, clinical and psychological factors associated with social anxiety in a sample of 85 people who had experienced TBI. Psychological variables (self-esteem, locus of control, self-efficacy) provide a significant contribution to the amount of explained variance in social anxiety (above that explained by demographic and clinical variables). Moreover, perceived stigma independently predicted social anxiety. The findings support the importance of psychological variables in the development of social anxiety, and the significant role of stigma highlights the need for both individualised and societal interventions. The third paper offers a critical appraisal of the research project, identifying key strengths and limitations in addition to discussing reflections on the process of conducting the study. The results and implications of the study are discussed, with particular focus on social models of disability.