genes show monoallelic parent-of-origin specific expression and have an important role in mediating adult behaviour. Previous research has indicated that maternally expressed Nesp and paternally expressed Grb10, which are expressed in overlapping brain regions, may have a role in mediating risk-taking and/or impulsive behaviours. Impulsivity and risk taking are natural parts of human behaviour; however pathological levels of impulsivity and risk-taking are recognised as clinical traits of many psychiatric disorders. The aim of the current research is to explicitly test whether these two oppositely imprinted genes influence impulsivity and/or risk-taking behaviour in mice by examining mouse models that lack functional copies of paternal Grb10 (Grb10+/p) and maternal Nesp (Nespm/+) in a number of tests of impulsivity and risk-taking. Unlike previous findings in Nespm/+ mice, Grb10+/p mice had the same propensity to explore a novel environment as wild type (WT) controls. However, in a measure of delay-discounting behaviour it was discovered that Grb10+/p mice were less likely to discount delayed rewards. This is in contrast to previous work with Nespm/+ mice, which discounted delayed rewards more steeply. This is the first demonstration that oppositely expressed imprinted genes antagonistically affect behaviour. To further explore these behaviours, a novel test of risk-taking was developed. Using predator odours a perceived ‘risky’ environment was created in order to measure the decision between fear and reward seeking. Using the Predator Odour Risk-Taking (PORT) task it was demonstrated that Nespm/+ and Grb10+/p mice showed comparable levels of risk-taking behaviour to WT littermates. Finally, immunofluorescence was used to discover that Nesp55 and Grb10 are not only expressed in the same brain regions, but are co-expressed in some cells, particularly in serotonergic neurons. This suggests that these imprinted genes may be influencing delay discounting behaviour via the same integral neurotransmitter systems.

Huntington’s disease is an autosomal dominant neurological disease caused by an elongated CAG repeat in exon 1 of the huntingtin gene. There is currently no cure and treatments are limited. The genetic mutation causes selective cell death of the medium spiny neurons which reside in the striatum of the basal ganglia. Current disease models don’t necessarily recapitulate all aspects of the human disease and so alternatives are needed. The advent of induced pluripotent stem cells (iPSC), has allowed for HD patient specific pluripotent stem cells to be derived, hence differentiation of these cells in vitro could provide a disease model for drug testing and investigation of disease pathology. Current protocols for differentiation of pluripotent stem cells into medium spiny neurons (MSNs) are often inconsistent and lead to low yields of MSNs. Directing differentiation through forced expression of transcription factors has been used to differentiate neurons from fibroblasts and pluripotent stem cells, often with increased efficiency. Utilising transcription factors vital in post-mitotic MSN development, this study has aimed to produce MSNs in vitro, by transfection of transcription factors or combinations thereof in a multicistronic plasmid into ventral forebrain neural progenitors. This study has involved the cloning and expression of 5 different transcription factors important in MSN development in iPSC-derived neural progenitors. Two of these transcription factors; NOLZ1 (ZNF503) and ISL1 were further investigated for their ability to differentiate neural progentiroes into MSNs. This study showed that transfection of ISL1 enabled differentiation of neurons to produce a higher proportion of cells resembling MSNs, characterised by co-expression of the MSN markers DARPP32 and CTIP2 and expressing FOXP1. The combination of NOLZ1 and ISL1 in transfection improved functional maturation of neurons, becoming increasingly spontaneously active and increased excitability, as well as responding to GABA and NMDA, with dopamine D1 agonist enhancement of NMDA currents.

The transcriptional coactivator PPARgamma coactivator 1alpha (PGC-1α) is a regulator of mitochondrial biogenesis and function and is decreased in the striatum of patients with Huntington’s Disease (HD). HD is an autosomal dominant neurological disorder caused by a polyglutamine repeat in the huntingtin protein which leads to degeneration of striatal and cortical tissues. PGC-1α undergoes targeted downregulation by mutant huntingtin protein (mtHtt) and PGC-1α knockout mice have striatal lesions similar to HD transgenic mice. Exogenous PGC-1α partially reverses the toxic effects of mutant huntingtin in cultured striatal neurons while in vivo administration of PGC-1α to the striatum in a mouse model of HD reduces neuronal volume loss. Synaptic N-methyl-D-aspartate receptor (NMDAR)- activity can drive the expression of PGC-1α which is neuroprotective against oxidative and excitotoxic stress in vitro whereas extrasynaptic NMDAR expression is increased in HD. Excessive NMDAR activity, specifically through extrasynaptic rather than synaptic NMDARs, leads to excitotoxic death in neurons and its regulation has been targeted in the search for therapeutic interventions for multiple neurological disorders. The data presented in this thesis show that the repression of PGC-1α by mtHtt may be significant in the dysregulation of NMDARs in HD. Both PGC-1α knockdown and mutant huntingtin are found to increase extrasynaptic NMDAR activity and excitotoxicity in a non-additive way, suggesting common regulatory mechanisms. Furthermore exogenous PGC- 1α expression is sufficient to reverse this increase in extrasynaptic NMDAR currents and excitotoxicity by mtHtt. This thesis adds mechanistic insight into previous understanding of the synergistic roles of mtHtt, NMDAR activity and PGC-1α in HD. Finally, we show that chronic knockout of PGC-1α in the PGC-1α(-/-) mouse causes distinct alterations in glutamatergic signaling that do not mimic the observation of acute knockdown of PGC-1α. We propose that the loss of PGC-1α in a number of neurological disorders contributes to concurrent increases in aberrant glutamate signaling and excitotoxicity in these diseases.

Background: A history of complex trauma alters basic self-structure, attachment system and core areas of interpersonal functioning and relationships. There is increasing recognition of the high proportions of complex trauma histories within substance misusers and limited research into the sequelae of complex trauma, particularly in relation to comorbid complex trauma and substance misuse. There is a distinct lack of adequate theory and guidelines for treatment. Research Aim: to explore psychologist’s experiences of and perspectives about their work with substance misusers with a history of complex trauma. Complex trauma is a term used to describe experience’s which arise from severe, prolonged and repeated trauma which is often interpersonal in nature. Courtois & Ford (2009) have defined complex trauma as “involving stressors that: are repetitive or prolonged, involve direct harm and/or neglect and abandonment by ostensibly responsible adults, occur at developmentally vulnerable times in the victim’s life, such as early childhood, have great potential to compromise severely a child’s development.” (p1). The prototype trauma that was first described under the term complex trauma was child abuse and neglect. Method: Semi-structured interviews were conducted with eleven clinical and counselling substance misuse psychologists working across four health boards in Central Scotland. The data was analysed using Interpretative Phenomenological Analysis (IPA). Results: Six main superordinate themes emerged from the data: 1. Challenges in negotiating therapeutic relationship; 2. Balancing relational forces; 3. Walking the tightrope of comorbidity; 4. Conceptual dearth (surrounding complex trauma); 5. Emotional impact of Work, and, 6. Core role of therapeutic relationship (in treatment and recovery). Discussion: Participants accounts suggest there are many risks to balance as well as paradoxes inherent in this type of work. The nature of a history of complex trauma means that often clients have difficulties with attachment and relational aspects in their lives, which in turn affect their engagement in the therapeutic relationship. The findings of this study suggest that it is precisely because relationships seem so threatening and challenging for these clients, that the therapeutic relationship appears to form such a vital role in the therapeutic treatment and recovery process for these client.

The object of this thesis is to consider the conceptions of Dissociation and Repression with a view to determining in what way, if any, the processes are related to one another. These two conceptions have played a part of unrivalled importance in modern psycho-pathology, but no satisfactory attempt seams to have bean made to determine the exact nature of their relationship to one another. The conclusions reached in this thesis regarding their relationship constitute, so far as the writer is aware, an original contribution to the subject.

Aims: Friendship plays an important and central role in adolescent life. This thesis was conducted in two parts to address two broad aims relating to friendship in adolescence. The first aim was to establish what is currently known about the impact of perfectionism on adolescent interpersonal relationships. Specifically, it was of interest to determine whether perfectionism exerts a negative influence on adolescent friendships. The second aim was to explore the friendship experiences of adolescents diagnosed with an eating disorder (ED) in order to address a significant gap in the current literature. Method: A systematic review of the literature relating to perfectionism and interpersonal functioning in adolescence was carried out with a view to addressing the first aim. With regards to the second aim a grounded theory study was conducted with adolescents currently in treatment for an eating disorder. The young people were asked about their experiences of friendship and emerging concepts were followed up in a concurrent process of data collection and analysis. Results: The systematic review highlighted an absence of research on interpersonal functioning and perfectionism in adolescence, with only seven studies identified that met inclusion criteria. The results were further complicated by inconsistencies in the conceptualisation of perfectionism in the identified studies. The empirical study uncovered the efforts that adolescents go to to achieve acceptance in their friendships. It also revealed that the development of an ED is experienced as creating distance in adolescent friendships. This affects both the actual amount of time that young people spend with their friends as well as the emotional connection that they are able to feel in their friendships. Conclusions: There is a need to reconsider the conceptualisation of perfectionism in future research with a consistent acknowledgement of the interpersonal dimensions of the concept. It is important to acknowledge the significant impact that ED development can have on adolescent relationships. Young people may require support to address these difficulties and preserve their friendships to avoid long term negative consequences.

Background: Evidence for the effectiveness of psychological treatments for sex offenders with learning disabilities is far from overwhelming. Qualitative studies can augment quantitative research by providing insight into the experiences of those who receive such treatment. There are a number of qualitative studies of the views of offenders but few that focus on the views of those with learning disabilities. Method: A systematic review was carried out of qualitative studies of the views of sex offenders, with and without learning disabilities, about their experiences of treatment. An empirical study, using Interpretative Phenomenological Analysis, explored the views of men with mild learning disabilities about one particular group treatment. Results: The review identified that a supportive atmosphere, good therapeutic relationship, trust and positive peer interactions were highly valued. Some elements of treatment, such as offence disclosure, were seen as both difficult and helpful. In the empirical study, themes regarding offence disclosure and trust were also identified. In addition, treatment was characterised as being about giving and receiving advice. Participants struggled with some of the other concepts used in treatment but described gains including becoming a mentor and developing a sense of mastery. Most strikingly, participants described needing extensive time in treatment in order to gain benefit. Over time they moved from feeling anxious and angry about treatment to feeling positive, supported and trusting. Conclusion: Sex offenders with learning disabilities may need long-term treatment programmes in order to effect change. Treatment providers should be sensitive to offenders’ feelings of initial anxiety and anger.

There is considerable responsibility on the clinician to identify sex offenders who may potentially commit more serious sexually violent behaviour and an increased demand for evidence based risk assessments (Macpherson, 1997; Thomas-Peter and Warren, 1998). Offenders who commit non-contact sexual crimes are traditionally classified as harmless despite the significant minority who escalate in offence severity towards more violent sexual offending. Forty convicted male sex offenders were classified as non-contact or contact sexual recidivists. Non-contact recidivists had a history of non-contact sexual offending on two or more occasions. Contact recidivists had a history of noncontact offending and had recidivated with a contact sexual offence. Groups were compared on the Sexual Violence Risk-20 (SVR-20: Boer et al. 1997) and the Psychopathy Checklist: Screening Version (PCL: SV: Hart et al. 1995). Psychosexual variables, criminal history and clinical risk factors were also coded using a multi-variable assessment model. A retrospective-prospective comparison successfully used by Quinsey et al. (1995) was performed between non-contact and contact recidivist groups. Factors that discriminated between non-contact recidivists and contact recidivists were primarily historical in nature, reflecting fixed or relatively stable characteristics. Significant differences between non-contact recidivists and contact recidivists were observed on total PCL: SV scores and psychosocial factors of the SVR-20 including sexual deviation, a history of childhood victimisation and past nonviolent offences. Contact recidivists were significantly younger than non-contact recidivists at first non-sexual offence and were significantly more likely to have a history of homosexual offending. A high level of interrater reliability on the SVR-20 and PCL: SV was observed. Suggested revisions to several iten1s of the SVR-20 and methodological considerations are reported. The research demonstrates that a progressive pattern of sexual offending from noncontact sexual offending to contact sexual offending is reliably associated with a combination of risk factors. The study offers the potential for early detection of a more serious escalation in sexual offending to allow for the possibility of supervision and clinical risk management.

Evidence from multiple studies suggests that regulation of emotions and intensity of affect may be relevant to understanding disordered eating. Emotion regulation concerns the ways in which emotions are managed in daily life, whereas Affect Intensity (Larsen et al., 1986) refers to individuals‟ typical emotional reactivity. The thesis examines emotion regulation and affect in females with eating pathology (subclinical as well as clinical), and looks at ways dysfunctional regulatory strategies may be improved. The main objective of the present research was to look at the influence of experimentally-induced positive affect on the choice of emotion management strategies. Study 1 looked at typical Affect Intensity and emotion regulation in a sample of subclinically eating-disordered University of Edinburgh students. This study examined functionality of regulatory strategies, typical intensity of affect, and the effects of experimentally induced happiness and sadness on the two. Study 2 introduced the construct of creativity into the discourse on emotions and psychopathology, and looked at creative tendencies in relation to Affect Intensity, emotion regulation and psychopathology (anxiety, depression and sub-clinical eating pathology). Study 3 looked at the effects of Positive Psychology Interventions (PPIs) on emotion regulation, life satisfaction, anxiety and depression in a subclinically eating-disordered group and controls. Studies 4 and 5 were carried out in order to test and extend the results of Studies 1 and 3 with a clinical sample. In Study 4, emotion regulation, Affect Intensity and the immediate post-test effect of happiness on emotion regulation and life satisfaction were examined in females clinically diagnosed with eating disorders (i.e. anorexia nervosa, bulimia nervosa, and EDNOS). Study 5 looked at how longitudinal happiness induction influenced emotion regulation, eating behaviours and life satisfaction in eating-disordered individuals. One of the main findings across the studies was that females with subclinical and clinical forms of eating pathology tended to experience negative emotions of high intensity, and used predominantly dysfunctional regulatory strategies to manage them. Another important finding was that experimentally-induced positive emotions improved emotion regulation, and encouraged participants to choose healthier affect management strategies. The studies, their implications and contribution to theory and treatment of eating disorders are discussed.

Epileptic seizures are often un-witnessed and can result in hypoxic brain damage or can be fatal due to injuries, status epilepticus or sudden unexpected death in epilepsy (SUDEP). The first aim of this thesis was to investigate some of the physiological parameters that accompany an epileptic seizure and may be useful in a seizure alarm system. The second aim was to investigate aspects of cardiac dysfunction during clinical and sub-clinical seizures that may be potential contributing factors in SUDEP. Percentage heart rate change and oxygen saturation were studied prospectively during 527 epileptic seizures in 50 patients aged from one-day full term neonate to 60 years with a variety of seizure types (absences, generalised tonic clonic seizures, myoclonic seizures, tonic seizures and focal seizures) and in normal physiological events (e.g. coughing, turning in bed). Higher percentage heart rate change occurred during epileptic seizures (21.8%) than during normal physiological events (16.4%) p<0.001. Diagnostic testing of clinically significant seizures i.e seizures that could potentially lead to serious consequences if left undetected (n=61) had a sensitivity of 91% and specificity of 75% when percentage heart rate change and hypoxaemia parameters were combined. Percentage heart rate change and oxygen saturation could be used as reliable indicators of a seizure when set at specific levels and distinguish clinically significant seizures from normal physiological events. These parameters can now be used to develop a reliable alarm system to detect epileptic seizures at night. Prolongation of QTc and increased vagal tone may be possible mechanisms underlying SUDEP. Corrected Q-T cardiac repolarisation time 5 minutes before and throughout 156 epileptic seizures were analysed using four corrective formulae (Bazett, Hodge, Fridericia and Framingham). All formulae indicated statistically significant lengthening of the corrected Q-T during epileptic seizures (p<0.001) compared to pre-seizure values. All formulae agreed that the greatest lengthening of the corrected QT beyond normal limits occurred during right temporal lobe seizures in two patients. Reflex and tonic vagal activity utilising R-R intervals was assessed in 33 sub-clinical seizures occurring during stages 3 or 4 sleep and was compared to matched counts of R-R interval non-ictal baseline studies from the same stage of sleep in each patient. Altered vagal activity occurred during total sub-clinical seizures compared to baseline studies (p<0.001). Lengthening of the corrected Q-T and changes in cardiac vagal tone during epileptic seizures may have a role in the patho-physiology of SUDEP.