This research explores the links between bipolar disorder and work. It focuses on the factors that impact an individual’s ability to work and explores whether a simple intervention to support all the key stakeholders (employees with bipolar disorder, line managers and occupational health professionals) involved in the process can be effective. This thesis involved three distinct parts. In the first part a qualitative focus group study explored the views and experiences of the employee, line manager and occupational health professional (OH) participants with respect to the management of bipolar disorder and work. Consensus was reached across the three groups on the main challenges to managing work and bipolar disorder and the solutions to overcome these. The three groups were in agreement on the key areas to be addressed in the intervention to meet the needs of each stakeholder group. In the second part, a qualitative questionnaire study explored the employment patterns and the impact of clinical and demographic variables on the employment outcome across a large sample of participants with a diagnosis of bipolar disorder. This study identified that individuals with bipolar disorder can obtain and sustain employment for prolonged periods, with some reporting sickness absence levels that match those without a mood disorder. It also identified the key clinical and demographical variablesbest associated with employment outcome, which included educational attainment, age of onset of contact with psychiatric services and length of longest psychiatric hospital admission. In the third part, informed by the literature review and focus group findings, the intervention 'Working With Bipolar' was developed that aimed to improve the interactions and conversations between the three key stakeholders in regard to the management of bipolar disorder and work. This intervention was well regarded among the target users and allowed positive and constructive ideas for change.

The striatal neuronal populations comprise medium spiny projection neurons (MSNs) and GABAergic and cholinergic interneurons. Huntington’s disease (HD) involves massive degeneration of striatal neurons. The derivation of MSNs and interneurons from human pluripotent stem cells (hPSCs) would allow modelling of striatal function and HD in vitro, as well as provide a viable source of tissue for cell replacement therapy. Our lab has previously demonstrated that Activin A can induce MSN fate in hPSCs, and that these cells can survive and differentiate in vitro and in vivo. In this study, it was found that this effect occurs via the Activin receptor, independently of SHH signalling. Furthermore, blockade of BMP signalling accelerated MSN differentiation. Electrophysiological analysis demonstrated their potential to acquire functional membrane properties and synaptic activity in vitro. Wnt inhibition and SHH activation have been shown to pattern hPSCs into medial ganglionic eminence (MGE) progenitors and cortical interneurons. Both cortical and striatal interneurons are born in the MGE. This thesis presents the first account of generating MGE progenitors for the purpose of producing striatal interneurons in vitro. They expressed subtype markers such as parvalbumin, somatostatin, calretinin and choline acetyltransferase. When transplanted into neonatal rat striatum, hPSC-derived MGE progenitors migrated to the septum and hippocampus within 6 weeks. The majority of differentiated neurons became calretinin GABAergic interneurons, and a few in the striatum acquired cholinergic interneuron fate. Patch clamp analysis both in vitro and in vivo revealed functional neuronal characteristics and synaptic connectivity, although a more mature neuronal phenotype was achieved in vivo. In conclusion, functional striatal MSNs and interneurons can be generated using hPSCs, which will be invaluable for research into striatal function and dysfunction in HD and other striatum relevant disorders. They may also serve as a desperately needed therapy for HD, pending further preclinical studies in HD animal models.

Creative ideas are those that are both novel and useful. Creativity is considered to be a valuable social resource, which has supported the development of society in myriad domains. It has been suggested that behavioural indicators of creativity overlap with symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Indeed, there is some preliminary evidence to suggest that individuals with ADHD may be more creative than individuals without ADHD. The first chapter of this thesis outlines the relevant research and theory and presents the ‘creative advantage hypothesis’. Specifically it is argued that defocused attention in individuals with ADHD increases the likelihood of unusual associations forming, thus increasing the likelihood of creative responses. The potential mediating roles of inhibition and delay aversion are also discussed. The second chapter of this thesis describes a study designed to test predictions of the creative advantage hypothesis. Parents of pupils in Year 8 were asked to rate their child’s level of inattentiveness and hyperactivity. Sixty six pupils completed a measure of figural creativity, inhibition and delay aversion in school. ADHD symptoms predicted creativity scores on one aspect of creativity, originality, and this effect was found in boys only. Inhibition and delay aversion were not found to mediate the relationship between ADHD symptomology and creativity in boys. Limitations and implications for Educational Psychologists and teachers are also discussed.

Low back pain is a common condition that will affect 80% of the population at some point in their lives. For the majority of people the pain and associated disability will be resolved and they will resume normal activities. For a small proportion of this group however, the condition will remain unresolved with associated long-term pain and disability; this is termed chronic low back pain (CLBP). The costs associated with CLBP are high both physically and emotionally for the individual, and in terms of the economic burden placed on society pertaining to healthcare costs and lost productivity. CLBP is a multifaceted condition. Whilst a biopsychosocial model of care, as opposed to the traditional biomedical model, is advocated as the best approach for its management it has been suggested that the impact on the self-concept and identity of individuals with this condition has not been fully explored or addressed. This study employed a biographical approach with the aim of understanding the impact on the lives and identities of men living with CLBP. Five men were recruited and in-depth interviews were undertaken which were audio-recorded, transcribed verbatim and analysed thematically. The identity of all the participants in the study had been affected by CLBP. Clear themes emerged that included feeling defined by their CLBP, experiencing feelings of frustration and anger, the inability to retain their masculine role, the impact on fatherhood, public and private identities, physicality and feeling a liability or burden to others. The support received from significant others was also highlighted. The participants detailed how exercise and education were major aspects in the management of their condition whilst resilience and the use of humour were also very apparent in their narratives as mechanisms to enable them to cope with CLBP.

No description available.

Organophosphate compounds have been widely developed as pesticides (e.g. paraoxon) and also as chemical warfare agents (nerve agents, e.g. sarin). These compounds rapidly inhibit the enzyme acetylcholinesterase (AChE), causing overstimulation within the cholinergic nervous system. If left untreated, this can be fatal. Current medical countermeasures to nerve agent poisoning consist of pretreatment with pyridostigmine and an emergency therapy comprising atropine, diazepam and pralidoxime. As well as a replacement pretreatment for pyridostigmine, physostigmine has been proposed as a component of a next generation of therapy to nerve agent poisoning, along with scopolamine and HI6. In animal studies, this therapy has been shown to lessen the level of incapacitation and increase survivability post poisoning with nerve agent. The exact mechanism of action of physostigmine in this combination is as yet unclear. The primary aim of this study was to test the hypothesis that the beneficial effect of physostigmine in the proposed therapy is due to reversible inhibition of AChE, thereby protecting it from irreversible inhibition by nerve agent. To test this, extracellular field potentials were recorded from the molecular layer of the dentate gyrus in an in vitro slice model developed from the guinea pig. This response was shown to be modulated by the application of physostigmine and the nerve agent sarin and interactions between the two inhibitors were characterised. The results provided evidence for protection of ChE by physostigmine. The functional response (field potential) was related to cholinesterase activity measured in slices exposed to sarin. This is the first evidence of the mechanism of action of physostigmine protection against nerve agent in the CNS. Not only will these results support the use of physostigmine as a pre-treatment, it also supports its use as a possible immediate therapy.

This dissertation considers coping and psychological well-being in informal carers of stroke survivors with aphasia. Firstly, a literature review examines the main problems reported by this group of carers, the coping strategies they use to manage these problems, and the links between coping and psychological well-being. This is followed by an empirical paper which reports on a study investigating how informal carers of stroke survivors with aphasia cope with communication problems, and examining the links between coping and an aspect of psychological well-being - depressive symptoms. Further, this study also explores the question of how best to measure how carers cope with communication problems, by including questions specifically developed for this topic alongside a traditional coping inventory. As expected, the results demonstrated a relationship between coping strategies and depressive symptoms in this group of carers. The use of avoidant coping strategies was associated with increased symptoms of depression. No links were found between problem-focused coping strategies and depressive symptoms, however it was shown that coping by ‘positive reframing’ was linked with reduced levels of depressive symptoms. The study also found that a traditional style coping inventory gives a useful assessment of the pertinent coping strategies used by informal carers of stroke survivors with aphasia to manage communication problems. However this is usefully supplemented by more specific questioning about the use of avoidance and withdrawal. The study concludes with a discussion of the clinical implications of the results and where future research in this area would be beneficially directed.

Dementia affects over 750,000 people in the UK (Alzheimer’s society, 2003). Clinicians and healthcare managers report dissatisfaction with current healthcare options available for people with dementia (Stubbings & Sharp, 1999). Multisensory Environments (MSEs) utilising advanced sensory stimulating equipment targeting the senses, have been successfully used in dementia care, severe learning disabilities and palliative care (Baker et al, 1997). Despite this, no controlled studies have been conducted to explore the efficacy of this intervention on functional performance. This study explores to what extent, if any, MSEs influence function, mood and behaviour of people with moderate / severe dementia compared with a control activity (gardening). In addition, sensory needs were identified using the Adult Sensory Profile to explore whether sensory preferences are associated with improved performance. Participants were selected from people with a diagnosis of moderate / severe dementia. They were randomly allocated to one of two groups (MSE or gardening). Following baseline assessment, each participant attended their allocated intervention 3 times a week for 4 weeks. Assessment was carried out before and after each session using the Assessment of Motor and Process Skills (function) and the Neurobehavioural Rating Scale (mood and behaviour). Results revealed a significant main effect of intervention in both function and mood and behaviour. Sessional analysis revealed significant improvement in motor performance for the MSE group. Overall, both activities were found to improve function and mood and behaviour. Participants who attended the MSE group and improved significantly in function fell within the low registration quadrant of the sensory profile. This suggests that the MSE is more suitable for those who require increased sensory stimulation. This study supports the use of sensory activity for people with moderate / severe dementia and recommends the use of the PAL and Adult Sensory Profile to plan and facilitate activity.

Learning can be explicit or implicit. Explicit learning takes place intentionally, in the presence of factual task-relevant knowledge; whereas implicit learning takes place unintentionally, without concurrent acquisition of knowledge about task performance. The relative benefits of implicit learning have been well investigated within healthy populations. Research consistently demonstrates that skills learnt implicitly are more likely to be retained, and are more robust under secondary task load. However, study protocols tend to involve laboratory based activities, which do not take into account the complexities of motor learning in natural settings. Direct transferability of the findings to stroke rehabilitation is therefore questionable. Two factors in explicit and implicit learning are the concepts of attentional capacity and attentional focus. Attentional capacity refers to the ability to attend to and process incoming information, whereas attentional focus refers to the location of attention in relation to specific aspects of the task being performed. Theories propose that focussing on specific movements (internal focus) may actually constrain or interfere with automatic control processes that would normally regulate movement, whereas if attention is focussed towards the movement effect (external focus) the motor system is able to more naturally self-organize, resulting in more effective performance, and learning. An internal focus of attention is therefore allied to explicit learning; whilst an external focus of attention is allied to implicit learning. This research aimed to improve understanding of explicit and implicit learning within early gait rehabilitation post stroke; primarily through the development and testing of explicit and implicit models of learning interventions. It has comprised three phases; a review of the literature; an observational study to gain insight into current practice; and a feasibility study to test the ability of therapists to deliver interventions with a bias towards either an explicit or implicit approach. Therapists were found to favour the use of explicit techniques; internally focussed instructions and feedback statements were used in high quantities. Practice therefore appeared to be at odds with current evidence; albeit primarily from healthy populations. Guidance for the delivery of explicit and implicit learning models in clinical practice was developed, and then tested in a feasibility study. Therapists demonstrated the ability to change their practice to bias either explicit or implicit learning; both approaches were found to be acceptable to patients and therapists. Recommendations are made on the content and evaluation of explicit and implicit learning models in future research, and specifically, in a Phase II pilot study.

Background: Schizophrenia has long been considered to be remarkably heterogeneous, and there have been a number of attempts to identify sub-groups of this disorder which are more homogeneous. Nevertheless, most of these have not been used in either research or clinical practice to any great extent, because diagnoses by way of these strategies would be unstable over time and impractical. In such circumstances, the vulnerabilitystress model has led to the development of a new concept of sub-grouping schizophrenia into 4 sub-types – drug related, traumatic, anxiety, and stress sensitivity. This conceptualisation is quite promising, not only because it may provide stable and practical diagnoses, but also because the terminology used therein is useful when it comes to destigmatising those who are currently diagnosed with schizophrenia. Methodology: In order to adapt this concept for practical use, this project set out to develop a semi-structured interview for making diagnoses according to it. Thereafter, psychometric properties of the interview were examined. This assessment tool was then used to confirm the longitudinal stability of the diagnosis. In order to establish the construct validity of this classification system, it was examined if the anxiety and stress sensitivity sub-groups in this system were different in terms of their external validators. Three psychopathological variables – evaluative belief, fear of negative evaluation from others, and depression – were assessed in a cross-sectional study during this process of validation. Three other clinical variables – two for the duration of hospitalization and one for the risk of self harming – were also used in a retrospective cohort study for the evaluation of the predictive value of the differentiation. Results and conclusion: Both the English and Japanese versions of the semi-structured clinical interview for psychosis sub-groups (SCIPS) were developed to sub-group patients into 4 categories, and their reliability and concurrent validity were established. The 6 month stability of SCIPS diagnoses of the drug related, anxiety and stress sensitivity sub-types was also indicated through a longitudinal study. A preliminary analysis provided little evidence of construct validity. The risk of self harming was, however, suggested as being associated with a distinction between the anxiety and stress sensitivity categories when the SCIPS was applied to a broader range of psychosis, including schizophrenia and schizoaffective disorder.