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Effects of glucocorticoid overload on central regulatory systems involved in responses to stress : preclinical investigations into putative molecular targets in neuroimaging of stress-related mood disordersAhmad, Rabia January 2013 (has links)
Irregularities of the Hypothalamic Pituitary Adrenal (HPA) axis are implicated in stress-related mood disorders. The ensuing long-term elevations in circulating glucocorticoids are associated with neurobiological changes seen in depression. This thesis aims to identify some of the brain mechanisms by which exposure to chronic stress may lead to depression using a preclinical experimental approach. The role of the serotonin system in the aetiology of mood disorders is well established, although this is not considered to be the only factor which causes these mood disorders. Interactions between the serotoninergic, peptidergic and endocannabinoid systems in response to glucocorticoids have been proposed. As all three neurotransmitter systems are involved in the regulation of the HPA axis, they are implicated in the dysfunction which is seen in depression. Furthermore, oxytocin, vasopressin and endocannabinoids are known to influence serotonergic neurotransmission and therefore it is pertinent to understand how glucocorticoids directly and indirectly impact serotonergic neurotransmission. In this thesis, the effect of chronic exposure to corticosterone on the serotonergic system is determined and also the relative contribution of the peptidergic and endocannabinoid systems to stress-induced mood disorders is considered. In addition, glucocorticoid-dependant receptor changes in these systems are related to neurotransmitter activity in brain regions involved in responses to stress. This has not previously been studied nor have the simultaneous effects of glucocorticoids on the serotonergic, peptidergic and endocannabinoid systems. Here, preclinical approaches are applied to investigate the above mentioned receptor systems and their involvement in depression resulting from exposure to chronic stress. Administration of exogenous corticosterone (400 μg/mL) to rats for 21 days, via addition to drinking water, resulted in changes in expression of central 5-HT1A, oxytocin, vasopressin 1a and CB1 receptors. This dose was selected as it has previously shown to induce depression-like behaviour in rats and also hippocampal atrophy similar to that seen in depressed patients (Magarinos et al 1998; Donner et al., 2012). In order to understand how these changes relate to the central concentrations of endogenous ligands, the concentration of serotonin, 5-HIAA, oxytocin and vasopressin was also measured in brain tissue. Here, circulating corticosterone concentration was increased, as it is in chronic stress and in some depressed patients. Binding of the post synaptic 5-HT1A receptor was upregulated in response to chronic stress in the form of elevated corticosterone concentration without a concomitant change in serotonin turnover suggesting that elevated corticosterone exposure modulates the 5-HT1A receptor independently of serotonin turnover. Whereas presynaptic 5-HT1A receptor binding was unaffected. In addition, chronic corticosterone exposure, as can be seen in depression, resulted in a decrease in binding to the oxytocin receptor in the hypothalamus associated with an increase in oxytocin concentration suggesting possible internalisation of the oxytocin receptor in this region. Conversely, there was an upregulation of the oxytocin receptor in the septal nuclei and raphé, with no associated change in oxytocin content in the same regions. Moreover, vasopressin 1a receptor binding was increased in septal nuclei and PODG subregion of the dorsal hippocampus, but decreased in the 3 hypothalamus. There was no change in vasopressin content in any brain region sampled, suggesting that these may be independent of peptide concentration. For the CB1 receptor, elevated corticosterone concentration, indicative of chronic stress, resulted in a decrease in receptor binding was found in the striata and raphé after chronic corticosterone treatment. Taken together, in particular the effect on receptor binding in the raphé, the present data suggest that elevated corticosterone exposure may modulate serotonergic neurotransmission via the oxytocin and CB1 receptor. In addition, the hypothalamic peptidergic responses imply a potential role in glucocorticoid-induced dysregulation of the HPA axis. These changes may help further elucidate their respective roles in depression and stress related mood disorders. In conclusion, the work presented in this thesis shows that the response to glucocorticoids is multifaceted and that there are changes observed in multiple neurotransmitter systems which regulate the HPA axis. Thus, the combined effect of the neurotransmitter systems studied here is of relevance to stress related mood disorders.
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Weighing heavily on the mind : an exploration of how therapists construct and manage body weight within therapyGray, Claire January 2016 (has links)
This study sought to understand how dynamic and differential meanings of body weight are experienced and negotiated within therapy. Studies have demonstrated the operation of fat bias within therapy affecting clinical judgement and treatment planning (Brown & Rothblum, 1990; Davis-Coelho, Waltz & Davis-Coelho, 2000). Other than literature around eating difficulties (e.g. Bordo, 2009; Burns, 2004; Costin, 2009; Malson, 2009), there is a scarcity of research demonstrating how meanings of body weight shape the therapeutic process. There is however, research urging vigilance for the operation of body politics within therapy: culturally imposed oppressive meanings for the body that may inform embodied and subjective experiences within the therapeutic encounter (Allegranti, 2011; Soth, 2006; Totton, 2012). This research asked how are meanings of the body and body weight constructed by therapists? Using a constructivist grounded theory method (Charmaz, 2014) this study conducted 12 interviews with counselling psychologists and psychotherapists. The findings suggest that therapists construct a ‘self’ as a body in a space, interacting with meanings of body weight to claim an identity as a therapist. It demonstrates the existence of body weight prejudice in therapy settings, with some therapists sanctioning meaning-making in accordance with a culturally and institutionally approved body order.
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The effect of regular listening to preferred music on pain, depression and anxiety in older people in residential careCosta, Fiona January 2015 (has links)
Music can be particularly beneficial for older people, many of whom have conditions that compromise their quality of life. It can be accessed irrespective of cognitive or physical capacity and can be enjoyed until the end of life; it is inexpensive and readily available. However, despite the widespread belief in music’s therapeutic effects, it has proved difficult to accumulate sufficient evidence to satisfy health professionals of its potential benefits to health and wellbeing. This research evaluates the effect of listening to preferred music on the wellbeing of older people living in care homes. One hundred and thirteen participants were randomly allocated to either an experimental or a control group. The former, in addition to their usual routine, listened to 30 minutes of preferred music over a three-week period. Weekly assessments, using validated measures with some adaptation, evaluated levels of pain, depression and anxiety, each a common condition in this population. On completion of the programme, the groups switched over, thus enabling all participants to receive the potential benefits of the music intervention. Results showed statistically significant decreases for each dependent variable with the size of the effect being greater for depression and anxiety than for pain. There were no significant improvements for those in the control group. Thematic analysis of the qualitative data gave further insight into the various ranges of response to the music intervention and identified those most likely to benefit from regular listening: those who listen frequently, have had some previous engagement with music and who regard music as important. It also raised awareness of the challenges that may arise at this stage of life. It was concluded that listening to preferred music is able to benefit many of the care home population, although not all will benefit to the same degree.
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The role of positive schizotypy and traumatic life events in the emotional content of experimentally induced false perceptionsVickers, Monique January 2015 (has links)
Background: Positive schizotypy describes unusual perceptual experiences (such as hallucinations) and beliefs (such a delusional-like thinking) akin to those observed in schizophrenia. Previous evidence has suggested that positive schizotypy can predict false perceptual experiences in non-clinical participants during experimental tasks involving visual detection of fast moving words. However, little is known about the role of emotion as well as the emotional content of such laboratory-generated, false perceptual experiences. Furthermore, despite previous evidence on an association between schizotypy and traumatic life events, it remains unclear whether such traumatic life events would also have an impact on the number and content of laboratory-generated false perceptions. Aims: The aims were to replicate previous findings that positive schizotypy is a predictor of false perceptions (perceptual bias) in a word recognition task and to extend this in a number of novel ways: investigate false perceptions as a function of schizotypy under different conditions through experimentally manipulating the emotional content of target words; examine the emotional content of such false perceptual experiences; and examine the role of schizotypy and traumatic life events in the amount and the content of false perceptions, while controlling for subclinical traits anxiety and depression. Method: In Study I, a non-clinical sample (N = 121) completed standard psychological questionnaires and undertook a word detection task where a series of target words (of four emotional conditions: positive, neutral, threat-related, or trauma-related) or non-words were briefly displayed on a computer screen. The participants identified any target words they saw. Some reported false perceptions, i.e. words that were not among the target words. In Study II, professional therapists (N = 12) and non-therapists (N = 12) rated the emotional content of the false perceptions according to standard scales for emotional intensity and valence. Results: Positive schizotypy was a predictor of the number of false perceptions in line with previous findings. Participants reported fewer correct responses in the threat-related and trauma-related target word conditions than in the neutral and positive conditions. Furthermore, associations were found between positive schizotypy and emotional content (Emotional Intensity, Activity and Potency) of false perceptions as well as between positive schizotypy, early-age trauma and depression. Conclusions: These findings suggest that individuals with positive schizotypy are more likely to experience false perceptions and that their false perceptions have a higher emotional content. The results also confirm previous findings that negative emotion may interfere with perceptual and/or cognitive processes, and that early-age trauma may be a risk factor for schizotypy.
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The use of coping strategies by psychologists to prevent vicarious traumatisationTizzard, Christine January 2015 (has links)
The purpose of this study was to investigate the coping strategies used by psychologists working within the demanding field of trauma psychology. The research process seeks to investigate whether post session distress remains or whether it may be effectively processed. Are there strategies that psychologists use that stand out as major components in removing residue material? Central to this study was the requirement to obtain a rich account of the participants’ experiences in order to elucidate the depth of meaning behind their statements. To achieve this aim the phenomenological method chosen was the van Kamm method adapted by Moustakas (1994). Following careful ethical preparation, five consultant psychologists were recruited for the semi-structured interview process. The findings of the study indicate that the individuals concerned use a range of unconscious and conscious coping strategies to process traumatic material. These were either positive or negative. A variety of physical, emotional and cognitive strategies were used. The choice of therapeutic modality influenced processing strategy. A major finding of the study was the use of peer supervision as a first line coping strategy. Participants reported that there were often inadequate resources allocated for this. Peer supervision is helpful because the shared experience of working with traumatic material provides a normalising function. Traditional one to one supervision was generally viewed as unhelpful and often perceived as exacerbating the distress of participants. Findings indicate that despite the use of coping strategies, residue material often remains. Participants did express positive effects of working with trauma but these coexisted with lasting negative attribution changes. This research has implications for the training of psychologists, particularly in the development of coping strategies both within supervision and as a method of self-supervision. It also raises the question as to whether trauma work should be solely provided by teams.
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Theoretical underpinnings of overgeneral autobiographical memory and the relationship between rumination and executive control in adolescenceStewart, Tracy January 2016 (has links)
Introduction: This thesis examined the theoretical underpinnings of overgeneral autobiographical memory (OGM) and the directional relationship between rumination and executive control at a time associated with heightened risk of depression. Specific attention was given to the subcomponents of rumination (brooding rumination and reflective pondering) and executive control when processing emotional and non-emotional information in an attempt to explain inconsistent findings in the literature. Providing insight into the developmental processes involved in autobiographical memory may help explain how OGM develops and is maintained. Method: Three studies entailing a mixed methods design formulated the methodology in this thesis and included: a systematic review of the CaR-FA-X model specific to child and adolescent populations and quantitative prospective research studies with school based adolescent samples. Results: Partial support was found for the CaR-FA-X model through the systematic review: strong support was found for capture errors and trauma exposure as well as interactive effects between rumination and executive control. Importantly, the mechanisms of the model manifest themselves differently depending on the clinical status of populations. The quantitative studies conducted with adolescents in community settings revealed that high levels of reflective pondering moderated the relationship between executive control for emotional information and OGM. Lower executive control when processing emotional material (reflected by larger switch costs) predicted less OGM, but only when reflective pondering levels were high. Lastly, findings indicated that rumination preceded executive control and demonstrated that reflective pondering was predictive of greater executive control (reflected by lower switch costs) for emotional information over time. Results were independent of age, gender and symptoms of anxiety and depression. Conclusions: Partial support for the CaR-FA-X model was found for child and adolescent populations, and findings highlighted important moderating factors. Reflective pondering may serve as a protective factor against OGM and lower levels of executive control when processing emotional information. Recommendations, refinements to theoretical models, implications and limitations are discussed.
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Automatic and intentional imitation : experiments with typically developing adults and adults with autism spectrum disordersLeighton, J. January 2007 (has links)
There are four main theories addressing the core mechanisms of imitation. Two of these theories suggest that imitation is mediated by a special-purpose mechanism and two suggest that it is mediated by general learning and motor control mechanisms. The main purpose of this thesis is to examine whether the question of how we imitate is best answered by specialist or generalist theories. In order to do this, experiments have been carried out using both intentional and automatic imitation paradigms. These paradigms have been used to examine imitation skills both in typically developing individuals and individuals with autism spectrum disorder (ASD). The first empirical chapter examines the role of goals in imitation. Specialist theories claim that goals play an integral role in explaining how we imitate. Some of the best evidence in support of this view is provided by error patterns generated in the pen-and- cups task. However, the results from variants of the pen-and-cups task, presented in this chapter, are more consistent with the idea that general processes, rather than goals, guide imitative behaviour. Chapters 3 and 4 examine imitative abilities in ASD using intentional and automatic imitation paradigms in order to ascertain whether there is an imitation specific impairment in ASD. Such an impairment would appear to be consistent with specialist theories of imitation. However, the findings from these chapters imply that the basic mechanism mediating imitation is not impaired in ASD, and that poor performance on complex intentional imitation tasks in ASD may be due to more generalised deficits, not specific to imitation. The final empirical chapter addresses effector specificity in imitation and whether this phenomenon can distinguish between specialist and generalist accounts of imitation. Using an automatic imitation paradigm, partial effector specificity is demonstrated, which is consistent with claims made by generalist theories. The first three empirical chapters therefore challenge some of the evidence that has been put forward to support specialist theories, and the final empirical chapter provides some specific support for generalist theories. Thus, the findings reported in this thesis are consistent with the hypothesis that imitation is mediated by general processes rather than by a special-purpose mechanism.
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Combining advanced MR techniques to investigate mild Traumatic Brain Injury and its cognitive consequencesCroall, Iain David January 2015 (has links)
Mild Traumatic Brain Injury (TBI) is a major health concern due to its high incidence and lasting cognitive consequences for the patient. Diffuse Axonal Injury (DAI); diffuse damage to axons caused by inertial forces during the TBI, is hypothesised to be a leading cause for these impairments. MRI-based research which has examined mild, acute cases has produced findings which indicate that the mechanisms and progression of mild TBI may be unique and not simply a less pronounced version of severe TBI. This thesis describes a set of experiments which used a variety of advanced MRI techniques to examine the physiological presentation and progression of mild TBI, and how this related to cognitive outcome. Forty-four mild and 9 moderate TBI patients were recruited an average of 6 days post-injury, scanned using a variety MRI techniques and administered a neuropsychological test battery. Twenty-three of these patients (18 mild and 5 moderate) returned one year later and repeated all testing. Thirty-three matched controls were also recruited and given the same set of tests. At the acute time-point patients underperformed on a variety of cognitive tests, although performance at the chronic time-point had normalised compared to controls. The distribution of visible lesions (as identified on quantitative T1 / T2 and T1W scans) was found to be similar to patterns previously reported in severe patients. Results also indicated more lesions to be related to greater acute cognitive deficit. Diffusion Tensor Imaging experimentation revealed a number of unexpected, cognitively-relevant metric changes at the acute and chronic time-points. Magnetic Resonance Spectroscopy investigation also showed a number of unusual metabolite concentration changes and also found these to relate to cognitive functioning. Novel hypotheses were formed from these findings. This work has demonstrated a number of cognitively-relevant physiological changes following TBI which appear unique to mild injury.
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Quantitative imaging in epilepsy (PET)McGinnity, Colm Joseph January 2013 (has links)
Introduction Epilepsy is a heterogeneous collection of neurological diseases characterised clinically by recurrent seizures. Pre-clinical models implicate derangements in ligand-gated receptor-mediated neurotransmission in seizure generation and termination. In this thesis, the author quantified activated N-methyl D-aspartate- and opioid peptide receptor availability in adults with focal epilepsy. Methods This thesis consists of three positron emission tomography (PET) studies of adults with focal epilepsy, using [18F]GE-179 (activated NMDA receptors) and [11C]diprenorphine (DPN; opioid receptors) radioligands. A novel resolution-recovery technique, Structural Functional Synergistic-Resolution Recovery (SFS-RR), was applied to pre-existing paired [11C]DPN PET datasets acquired from adults with temporal lobe epilepsy (TLE). Activated NMDA receptor availability was quantified in adults with frequent interictal epileptiform discharges (IEDs), by regional compartmental modelling and model-free voxelwise analyses. Statistical parametric mapping was used to identify significant differences in volumes-of-distribution (VT) between populations. Results [18F]GE-179 had good brain extraction with a relatively homogeneous distribution and moderately-paced kinetics in grey matter. The two brain compartments, four rate-constants model best described the radioligand's kinetics in grey matter. Global increases in [18F]GE-179 VT were seen for seven of 11 participants with frequent IEDs. Focal increases in [18F]GE-179 VT of up to nearly 24% were also identified for three of the 11 participants. A post-ictal increase in [11C]DPN VT was identified in the ipsilateral parahippocampal gyrus. Discussion This first-in-man evaluation of [18F]GE-179 evidenced several properties that are desirable in PET radioligands, but the specificity of binding requires further characterisation. The results suggest focal increases in activated NMDA receptor availability in participants with refractory focal epilepsy, and also post-ictal increases in opioid peptide availability in the parahippocampal gyrus in TLE. Both findings may have pathophysiological relevance, and illustrate the potential of quantitative ligand PET with advanced post-processing to investigate changes in inhibitory and excitatory receptor systems in the epilepsies in vivo.
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Compassion for the self and well-being : psychological and biological correlates of a new conceptKirschner, Hans January 2016 (has links)
This thesis applied a triangulation of behavioural and physiological methods to explore potential psychological and biological correlates accompanying the short-term cultivation of self-compassion in both healthy and clinical samples. Drawing on theory and previous research on self-compassion, the aim of this thesis was to investigate if the cultivation of self-compassion enhances positive affiliative affect and a greater tendency to prefer positively valenced information about the self. It was hypothesised that increased positive affiliative affect would be accompanied by the activation of the soothing and contentment system, a system characterised by the dynamic balancing of the sympathetic and parasympathetic nervous systems. A series of four experimental psychophysiological studies in healthy individuals and those with a history of recurrent depression was conducted. The results of these broadly supported this hypothesis. Detailed exploration of the results indicated that the proposed protective effects of self-compassion via the stimulation of the soothing and contentment affect system and access to a more positive perception of the self may rely on important individual differences in levels of self-criticism, insecure attachment, and history of childhood adversity and might be made more challenging when there is an underlying psychopathology such as recurrent depression. In this context, the results of this thesis indicate that more indirect approaches to cultivate self-compassion like the compassionate body-scan or mindfulness-based cognitive therapy (MBCT) might enable these individuals to access and activate the soothing and contentment system. Taken together, this research suggests that the cultivation of self-compassion might contribute to resilience in the face of negative thoughts, memories, feelings and depressive symptoms, because it is accompanied by psychophysiological response patterns that are suggested to be associated with adaptive emotion regulation and self-soothing in times of distress.
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