Four genes, connected to either the inflammatory or cardiovascular system or both, were investigated for association with late onset AD in up to 180 late onset cases and 180 age- and sex-matched controls. The I allele of DCP1 has previously been reported to be associated with AD although no associations was detected in this study. Six other polymorphisms within the gene were also studied but yielded no positive genotypic, allelic or haplotype associations. The other genes studied, TACR2, a peptide receptor that maps to a region of suggestive linkage on chromosome 10, ECE1, a potent vasoconstrictor which also maps to region of suggestive linage on chromosome 1 and PI12, a serine protease inhibitor that can form amyloidogenic fragments, were screened for polymorphisms. Fifteen polymorphisms were discovered (five coding) with only one two-marker haplotype in ECE1 (p= 0.001) and a polymorphism upstream of TACR2 (p = 0.05) showing statistically significant association. Neither association retained statistical significance after adjusting for multiple testing.

Alzheimer's disease is a neurodegenerative disorder characterised by progressive memory impairment, a decline in language function and a variety of behavioural symptoms. The majority of AD cases have an age at onset above 65 years and exhibit no clear pattern of inheritance. The only known genetic risk factor this late onset AD, LOAD, is the [Special character omitted]4 allele of the apolipoprotein E gene on chromosome 19. There is significant evidence of linkage to LOAD on chromosome 10q21-23. Therefore, nine candidate genes that map to this region were examined as susceptibility loci for the disease. In addition, a purely functional candidate, ADAM12, was examined on the basis of its homology to α-secretase enzymes, 58,752 basepairs of genomic sequence were screened by DHPLC, covering all exons, intron-exon boundaries and putative promoter regions, and 89 polymorphisms were detected. An additional 25 SNPs were identified from a SNP database. A two-stage strategy was employed. Variants were initially tested for association with AD by genotyping them in a small case-control sample, either in DNA pools or individually. Polymorphism showing a significant  difference between cases and controls were carried forward to the second stage and individually genotyped in a larger sample. A number of SNPs initially gave a positive result but after individual genotyping in a larger sample only 2 SNPs in the ADAM12 gene showed evidence for association with LOAD. As a large number of polymorphisms were examined, this may be a false positive finding, but this gene certainly warrants further investigation.

This work highlights phenotypic heterogeneity and how this may index underlying aetiological heterogeneity. It also indicates the importance of environmental variables and investigating Gene x Environment interactions in molecular genetic studies of ADHD.

Being a parent is generally accepted to be a difficult but rewarding job. For those individuals who combine parenthood with an emotionally demanding career, such as clinical psychology, this experience may be magnified. Exploring the experiences of parents who also work in the field of clinical psychology offers a meaningful insight into the challenges and positive rewards inherent in managing work and family life. Chapter I consists of a narrative review of the literature exploring the issues of balancing work and family life for psychologists. The barriers apparent in the literature, as well as the positive factors for achieving effective work life balance are considered. Barriers cited in the literature include the difficulties in meeting the demands of multiple roles, the influence of gender and negative individual factors. Positive influences on achieving effective work life balance included engagement in leisure activities, positive relationships, organisational support and positive individual factors. The clinical implications of this literature are discussed. Chapter II presents an empirical study conducted with psychological therapists who work within a Child and Adolescent Mental Health Service (CAMHS) and are also mothers. Nine psychological therapists were interviewed during the research. Following the use of the Interpretative Phenomenological Analysis (IPA), three superordinate themes emerged from the data. The findings consider the implications of shared experience when working with parents and the dilemma of managing the multiple demands of work and family life. The sense of re-evaluation of one’s own self-concept following becoming a mother is also discussed. Clinical implications are considered alongside suggestions for future research. Chapter III offers a reflective account of the challenges inherent in undertaking doctoral level training in clinical psychology whilst raising a young family. The implications for the role of clinical psychology as a discipline are considered as well as the impact on my own personal and professional development.

Emotions can influence creative thinking. The ability of people to have the emotions that augment creativity can therefore help them to achieve higher creative task performance. How to design interactive systems that can effectively make use of this potential is, however, still an unanswered question. To explore possible answers to this question we have developed two novel approaches to interactive systems that can be used to effectively hack into the emotion-creativity link. One approach we developed enables a system to hack into the function of motor expressions in emotion regulation, in order to regulate the emotions that happen spontaneously during a creative task. We demonstrate that embodied interactions designed based on motor expressions, while used to interact with a system, can influence an intended emotion, and thereby influence the relationship between emotion and creativity. The second approach that we developed enables a system to hack into the cognitive appraisal processes that help cause emotion during a creative task. We demonstrate that believable computer generated feedback about the originality of a user’s own ideas, can be manipulated to help cause an intended emotion, determine its intensity, and thereby also influence the relationship between emotion and creativity. The contribution of this thesis is the development of two novel approaches to interactive systems that aim to influence the emotion-creativity link and in particular the explication of the mechanisms underlying these approaches. The studies form a novel contribution to both interactive systems research and the creativity sciences.

Nightmares, a common sleep disturbance which provoke fearful awakening, have been found to be a significant predictor of suicidal thoughts and behaviours. The research presented in this thesis aims to firstly examine if nightmares are predictive of self-harm regardless of suicidal intent or motivation, and secondly to explore the psychological mechanism linking the occurrence of nightmares to self-harm. Chapter 2, an online survey, revealed that nightmares were a significant predictor of self-harm regardless of suicidal intent or motivation and that this relationship remained when controlling for the effects of depressive symptoms. High levels of nightmares were also associated with elevated levels of negative affect and defeat. Chapter 3 prospectively examined the direction of the predictive relationship between nightmares and self-injurious thoughts and behaviours (SITBs) through a 5-day diary study of undergraduate students. Nightmares unidirectionally predicted SITBs when controlling for depressive symptoms and negative affect. Mediation analysis revealed negative affect to be a partial mediator between nightmares and post-sleep SITBs. Chapter 4 explored differences in the linguistic content of nightmares in individuals with and without a history of self-harm, using nightmare reports prospectively obtained from participants taking part in the diary study. Contrary to the literature, participants with a history of self-harm did not report more words pertaining to death. Exploratory analysis investigating self-harm recency indicated a higher frequency of perceptual words such as ‘feel’ and body words such as ‘arm’ in participant with current self-harm (< 1 month) compared to those with a history of self-harm (> 1 month) and those without. Chapter 5 modelled the psychological mechanism linking nightmares to increased self-harm risk via structural equation modeling from survey data. This model incorporated negative affect, hyperarousal and a latent variable ‘self-harm cues’ building on our previous findings and the literature. Our retained model indicated that a 1 standard deviation increase in nightmare score increased the probability of participants having recently (< 1 month) engaged in self-harm. Chapter 6 tested the predictions of the model computed in the previous chapter using behavioural and psycho-physiological methodology. Psycho-physiological measures when exposed to negatively valenced stimuli did not reveal any differences between high and low nightmare participants, nor were differences observed in self-harm cue sensitivity. However, a medium effect was observed indicating the high nightmare group to be more sensitive to stressors. These findings are discussed in the context of the literature in Chapter 7. They provide novel insights into the relationship between nightmares and self-harm, and highlight the importance of negative affect and hyperarousal as reducing stress resilience in individuals at risk of deliberate self-injury.

The common mental disorders of anxiety and depression (CMD) impose a substantial burden on individuals and society. A current limitation for research into risk factors for CMD is that the Mental Health Inventory -5 MHI-5) a brief but widely used scale to measure of anxiety and depression was designed without a cut-point to identify cases of CMD. This thesis designed a web-based epidemiological study. Changes in Well-being to gather data from MHI-5 and the Clinical Interview Schedule – Revised (CIS-R), representing the ‘gold standard’ for CMD case classification. From a random sample of 10,000 people aged 18 to 74 years living in Caerphilly County Borough, Wales a total of 616 participants were recruited. Of these, 82 (13.4%) were classified as CMD ‘non-severe’ (CMD-NS) using a CIS-R score of 12-17 and 129 (20.9%) were classified as a case of CMD ‘severe’ (CMD-S) with a CIS-R score of 18 and over. In an analysis of paired CIS-R and MHI-5 scores, the corresponding cut-points on the MHI-5 scaled of 0-100 were <60 and <45 respectively. These cut-points were applied to baseline and follow-up survey MHI-5 scores in the Caerphilly Health and Social Needs Longitudinal Study dataset to classify cases. Logistic regression analysis showed the importance of younger age, a range of major adverse life events, and living in the most deprived areas as risk factors for the onset of CMD. Adverse employment transitions, moving to non-owner-occupation and becoming widowed were more strongly associated with older age groups and living in areas of high social cohesion. This thesis has shown the utility of web-based epidemiological studies in population mental health, determined cut-points on the MHI5 scale and demonstrated the importance of a wide-range of risk factors for change in CMD case status.

Visual perception is highly variable across healthy individuals and increasing evidence suggests that this inter-individual variation could be due to differences at the genetic, neurochemical, structural and neurophysiological level. Specifically, variation in the GAD1 gene (responsible for synthesising the majority of cortical GABA) has been associated with differences in the level of the inhibitory neurotransmitter GABA. In addition, differences in GABA and cortical structural parameters (surface area and thickness) have been shown to predict differences in neural gamma oscillations. However, these findings have not been replicated in large independent studies. Hence, Chapter 3 and 4 of this thesis combines the non-invasive neuroimaging tools MRI, MRS and MEG with genetic data to investigate the relationship between variations in genes, GABA, structure and gamma oscillations in the visual cortex of a large cohort of healthy individuals. Group differences in GABA, structure and gamma oscillations have also been reported between psychiatric populations (schizophrenia and bipolar disorder) and healthy individuals. However, differences in the direction of effect (increase or decrease) and no group differences have been found. Thus, Chapter 5 aims to further study these inconsistent findings by exploring group differences in GABA, structure and gamma oscillations between a healthy group and a schizoaffective bipolar disorder group. Lastly, inter- individual variation is also present in auditory perception but has received much less attention into the factors driving this variation. As in the visual system, similar links between neurochemical, structural and neurophysiological measures could be present in the auditory domain. Chapter 6 investigates the association between auditory gamma oscillations and auditory structural parameters in a healthy cohort.

Genetic variation in the gene ZNF804A has been shown to be related to risk for psychopathology, especially schizophrenia and bipolar disorder. The main aim of this thesis was to characterise the behavioural effects of Zfp804a, the mouse orthologue of ZNF804A, in order to understand more about how this gene influences brain and psychological functioning, and hence provide clues as to its possible role in mediating risk for mental disorders. Prior to this work, two ENU-mutant mouse lines had been generated from a DNA library of ENU mutagenised mice with two non-synonymous mutations selected as viable candidates for further investigation. The C59X mutation encodes a premature stop codon in exon 2, thought to lead to a functional null of the gene, and the C417Y mutation is missense, substituting cysteine for tyrosine in exon 4. A first series of experiments examined the early development of the ENU-mutant lines and showed no gross developmental abnormalities, although the C59X mutants weighed significantly less than their WT littermate controls at weaning and during adulthood. A comprehensive series of behavioural tests then assayed aspects of emotion, motivation, hedonia, sensorimotor gating and response control. In general, the C59X mutants showed the greatest effects, displaying reduced anxiety, anhedonia, and sensorimotor gating deficits, together with evidence of enhanced response inhibition. The C417Y mutants only showed selective effects in terms of enhanced motivation. The data dissociate between the effects of the two ENU-induced mutations of Zfp804a. Furthermore, the findings with the C59X mutants would suggest, a priori, that genetic variance leading to alterations in ZNF804A expression may be an important mechanism contributing to risk for psychopathology.

The three aims of my interdisciplinary thesis are: - To develop a conceptual framework for re-thinking the gestures of neuro-atypical young people, that is non-traditional and non-representational - To develop qualitative analytical tools for the annotation and interpretation of gesture that can be applied inclusively to both neuro-atypical and neuro typical young people - To consider the conceptual framework in terms of its theoretical implications and practical applications Learning to communicate and work with neuro-atypical young people provides the rationale and continued impetus for my work. My approach is influenced by the limited social, physical and communicative experiences of young people with severe speech and motor impairment, due to cerebral palsy (CP). CP is described as: a range of non-progressive syndromes of posture and motor impairment. The aetiology is thought to result from damage to the developing central nervous system during gestation or in the neonate. Brain lesions involve the basal ganglia and the cerebellum; both these sites are known to support motor control and integration. However, a paucity of theoretical research and empirical data for this target group of young people necessitated the development of both an alternative theoretical framework and two new tools. Biological Dynamic Systems Theory is proposed as the best candidate structure for the re-consideration of gesture. It encompasses the global, synthetic and embodied nature of gesture. Gesture is re-defined and considered part of an emergent dynamic, complex, non-linear and self-organizing system. My construct of Cognition-in-Action (C-i-A) is derived from the notion of knowing-as-doing influenced by socio-biological paradigms; it places the Action-Ready-Body centre stage. It is informed by a theoretical synthesis of knowledge from the domains of Philosophy, Science and Technology, including practices in the clinical, technology design and performance arts arenas. The C-i-A is a descriptive, non-computational feature-based framework. Its development centred around two key questions that served as operational starting points: What can gestures reveal about children’s cognition-in-action? and Is there the potential to influence gestural capacity in children?. These are supported by my research objectives. In my empirical study I present three case studies that focus on the annotation and interpretative analyses of corporeal exemplars from a gesture corpus. These exemplars were contributed by neuro-atypical young people: two adolescent males aged 16.9 and 17.9 years, and one female girl aged 10.7 years. The Gesture-Action-Entity (GAE) is proposed as a unit of interest for the analysis of procedural, semantic and episodic aspects of our corporeal knowledge. A body-based-action-annotation-system (G-ABAS) and Interpretative Phenomenological Analysis methodology is applied for the first time to gesture (G-IPA). These tools facilitate fine-grained corporeal dynamic and narrative gesture feature analyses. These phenomenal data reveal that these young people have latent resources and capacities that they can express corporeally. Iteration of these interpretative findings with the Cognition-in-Action framework allows for the inference of processes that may underlie the strategies they use to achieve such social-motor-cognitive functions. In summary, their Cognition-in-Action is brought-forth, carried forward and has the potential to be culturally embodied. The utility of C-i-A framework lies in its explanatory power to contribute to a deeper understanding of child gesture. Furthermore, I discuss and illustrate its potential to influence practice in the domains of pedagogy, rehabilitation and the design of future intimate, assistive and perceptually sensitive technologies. Such technologies are increasingly mediating our social interactions. My thesis makes an original and significant contribution to the field of cognitive science, by offering an ecologically valid alternative to tradition conceptualization of perception, cognition and action.