This thesis combines two research papers. The first paper is a systematic literature review investigating risk factors associated with suicidality in Huntington’s disease. The review discusses the importance of clinicians using the identified factors as ‘red flags’ when screening for suicide ideation so that either preventative measures can be put in place or psychological interventions provided to ameliorate any distress. The second paper is an empirical study which explores the concept of ‘rational suicide’ in Multiple Sclerosis (MS). It also investigates whether depression forms an important link between disability and suicide ideation, compares types of Progressive MS and examines whether there are differences in levels of suicide ideation for different disability types. The findings are discussed in terms of current literature, future research recommendations and clinical implications.

Two types of electrolytic growth processes have been investigated as possible means of controlling impedances in adaptive systems. One of these entails the growth of conductors by metallic deposition and the other the growth of insulation by anodic oxidation. The way in which the growth of a metallic dendrite changes the impedance of a cell has been determined, and it has been found that this depends very much on the shape of the cell. By restricting growth to narrow channels it has been found possible to reliably control the impedance of cells. The properties of devices employing this principle are described. The growth of insulating films on aluminium has been found to be another satisfactory method of reproducibly adjusting the impedance of a cell. The properties of these films and the impedance changes which take place during their 'formation' and 'erosion' are discussed. These films have special properties which make them suitable for use in the fabrication of devices containing many variable impedances in a single unit. The construction and properties of these devices are described. An adaptive system employing the growth of dendrites has been constructed, and trained to distinguish between four simple patterns. The design of this machine and the training procedure employed are given. Suggestions are made for future work and for other applications or electrolytic growth processes.

A form of apparent visual movement which occurs when spatio-temporally random visual noise is confined in an annular channel has been investigated. The phenomenon, known as the Omega Effeot, does not seem to be related to the phi-phenomenon, although there are formal similarities with observations sometimes made in certain stroboscopically illuminated fields. The period of omega movement was found to be independent of most of the statistics of the visual noise used to evoke it. Over 100 subjects were tested with a variety of stimulus-annuli. Although large individual differences occurred, the mean period and variance of most Ss did not generally vary, although there was some dependence on performance in the recent past. Significant sex differences were found in estimates of the mean period. The more of observation had little effect that could be measured. Simple, circular annuli evoked the clearest and most consistent reports of apparent movement. The two parameters which conditioned the mean period p were found to be the annulus diameter D and the channel thickness T. For large enough groups of' Ss , it was shown that p = K1 D log T + K2 log T + K3 D + K4 fitted the experimental data very closely. It was demonstrated that both changes in distance and changes in angle of regard affected the mean period, there existing a negative and a positive correlation, respectively. The former finding was in agreement with prediction, but the latter was not. It was postulated that the effect depends to at least some extent on the presence of long-range interactions which possibly exceed the limits normally found in the retina. Some suggestions are made for possible future work.

Neurons are the targets of injury and disease in many neurological conditions, and achieving neuronal survival/repair is a key goal for regenerative medicine. In this context, genetic engineering of neurons offers a platform for (i) basic research to enhance our understanding of neuronal biology in normal, disease/and injury conditions; and (ii) for regenerative medicine to enhance the functionality of neurons. Although, a wide range of attempts have been made to promote gene delivery to primary neurons, these cells are still difficult to genetically engineer, and current methods rely heavily on viral vectors which pose safety considerations. Magnetic nanoparticles (IONPs) are currently of great interest in regenerative medicine including for non-viral gene delivery by the ̳magnetofection‘ strategy, i.e when used with applied magnetic fields. This project aimed to examine (i) the influence of two novel uniaxial and biaxial oscillating magnetic field devices on primary neuronal transfection efficiency, and (ii) examine the safety of magnetofection using histological and electrophysiological studies. In order to do this, a robust protocol to derive primary cortical neurons was first established. A second issue is that surgical delivery of Neurons results in low survival. Additionally, most basic research has relied on neurons grown on ̳hard‘ substrates such as plastic, which do not mimic the mechanical properties of the in vivo microenvironment. To address these limitations, primary cortical neurons were grown in a 3-dimensional ̳soft‘ collagen hydrogel construct which can serve both as a protective cell delivery system and a ̳neuromimetic‘ substrate. The safety of the established protocol was evaluated by electrophysiological analyses on neurons. The findings demonstrate that the safety of magnetofection is magnetic field dependent, and at optimal conditions, electrophysiological properties of the nano-engineered neurons were normal. Secondly, I have shown that collagen hydrogels can support the 3D growth of neurons and electrophysiological studies can be carried out on the construct neurons; small differences were found between neurons grown on hard and soft materials. Finally, the amenability of genetic engineering of neurons within hydrogels using IONPs has been shown.

The increasing prevalence of suicidal behaviors in the United States inflicts massive emotional and economic costs in the United States (CDC, 2012). Efforts to detect and prevent these behaviors have not resulted in overall reduction of these costs, and could be enhanced with new approaches to assessing risk for specific suicide outcomes (Klonsky & May, 2014). Several contemporary theories of suicide make distinctions between suicide outcomes (i.e., suicidal ideation, suicide attempt, suicide death) that are often conflated in studies of suicide risk (Joiner, 2005; O'Connor & Kirtley, 2018). The present research, borne of these theories, sought to examine whether known demographic and psychiatric risk factors for suicide help distinguish between respondents of a nationally-representative survey measure, who reported either a history of suicidal ideation, a history of suicide attempt, or neither of these experiences. Significant differences were observed when comparing individuals reporting a history of attempt or ideation with individuals reporting no suicide history across many of these factors. Significant associations were also observed when comparing those reporting a history of ideation and those reporting a history of attempt, suggesting that these factors may provide some degree of incremental validity for the detection of risk, specifically for suicide attempt. Demographically, race/ethnicity and level of education yielded the most significant distinctions between those reporting a history of ideation and history of attempt. Psychiatrically, antisocial and borderline personality disorders and a history of mania yielded the most significant distinctions between those reporting a history of ideation and history of attempt. These results could be applied in developing screening measures for individuals at increased risk for making suicide attempts, which carry their own emotional and economic costs when not resulting in death, and are also highly associated with eventual mortality by suicide. These applications as well as study limitations will be discussed in detail.

Trata-se de um estudo de natureza exploratória descritiva, com abordagem qualitativa. O arcabouço teórico que subsidiou a construção dos pressupostos e a análise dos resultados foram problematizações da Nova História francesa, aliadas às contribuições da fenomenologia sobre o tempo vivido, visando à exploração histórica e à compreensão do fenômeno estudado. Quanto às técnicas ou procedimentos de pesquisa, utilizamos a história oral temática acerca do tempo no hospital psiquiátrico através da questão norteadora: “Como você registra o tempo aqui no Hospital?" e suas correlatas, “Há quanto tempo você está no Hospital?", “Como você passa o dia no Hospital?". Objetivamos investigar as estruturas de sustentação temporal de pacientes psiquiátricos indigentes, com história de mais de vinte anos de internação em manicômio, que não dispunham de calendários e/ou relógios, assim como, relacionarmos tais estruturas às práticas e aos agentes da cultura manicomial e relacionarmos a negação do tempo no hospital psiquiátrico tradicional à possibilidade de acesso ventilada pela transformação dos serviços de atenção em saúde mental (a instituição negada/inventada). Os resultados encontrados apontam para a predominância de um tempo que, embora “morto", se impõe na ausência de conectores convencionais (calendário e relógio), através de nostalgia, silêncio eloqüente, um distanciamento que oscila entre uma imediata justificação ou “aversão" ao tema. Os sujeitos da pesquisa denunciam uma temporalidade interceptada, uma “presença faltante" marcada pela vivência institucional, mas também por resquícios de um passado pessoal, onde o porvir, hoje, propugnado pela atenção psicossocial exige o “re-aprendizado" das formas de lidar com os mecanismos temporais que caracterizam a passagem do tempo na sociedade extramuro. / This is an exploratory-descriptive study using a qualitative approach. The framework that based the construction of hypothesis and results analysis were the contributions of French New History and phenomenology, enabling a history exploration and the understanding of the studied phenomenon. With respect to the research techniques and procedures, the author used oral history to analyze time at a psychiatric hospital through the guiding question: “ How do you feel time at the hospital?" and others related questions such as “How long have you been here?" , “How is your day at the hospital?". The aim of this study was to investigate the structures that base time to psychiatric patients with a history of more than twenty years of hospitalization, who did not have calendars and/or watches, as well as to relate these structures to practices, to the traditional hospital culture of denying time and to the possibility of access and changes in mental health services (from denied to an invented institution). The results point out the predominance of time, that although “dead", is present even with the lack of conventional connectors (calendars and watches), through nostalgia, eloquent silence, a distance that oscillates from an immediate justification to an “aversion" regarding the theme. The subjects of this research denounced an interrupted temporality, a “lack" marked by their institutional experiences but also with elements of their past, in which tomorrow and today, that are the basis of psychosocial care require the re-learning of coping ways with temporal mechanisms that characterize time flow in outdoors society.

This thesis contributes to the executive dysfunction account of autism by demonstrating that impairments in inhibitory control, an aspect of executive functioning, are partially responsible for deficits in the cooperative play of highfunctioning children with autism (HFA). As past research on whether inhibitory control is impaired in autism has been inconclusive, a meta-analysis of 42 empirical studies (57 effect sizes, total n = 2,256) was conducted, which provided clear evidence for impaired inhibition in HFA children. It was also found that the degree of impairment shown does not vary across measures of inhibition, which has important methodological implications for future research. Two experimental studies were carried out to directly test the link between inhibition and three components of cooperation: reciprocity, accepting the play partner's input, and fairness. In study one, HFA children in primary school and agematched typically-developing (TD) peers were tested on engaging in joint attention, theory of mind (ToM), measures of inhibition, and a cooperative drawing task. The groups did not differ on first-order ToM and joint attention, but HFA participants demonstrated poorer inhibitory control and less cooperative behaviour. Importantly, the degree of impairment in inhibitory control predicted reciprocity and accepting the play partner's input in HFA children. The second experimental study investigated whether poor inhibitory control can explain the well-established discrepancy between moral reasoning and actual sharing behaviour. A sample of HFA and TD children of primary school age completed a moral reasoning interview, inhibitory control tasks, and a Dictator Game. The results showed that while HFA children demonstrated age-typical levels of moral reasoning and sharing, inhibitory control emerged as the most important predictor of sharing behaviour, lending support to the hypothesis that the ability to suppress one's own desires is a prerequisite of acting considerately. The last study comprises a qualitative investigation of TD children's experience of engaging in cooperative play with their sibling who has a diagnosis of HFA. Six children between the ages of 5 and 11 were interviewed, and their reports analysed using interpretative phenomenological analysis (IPA). Five themes emerged: poor emotion regulation, restricted interests, and no acceptance of the playmate's contributions reduced the hedonistic value of joint play for the participants, but these were mitigated by appreciation for the HFA sibling's creativity and adjustment to the HFA sibling's behavioural atypicalities. These results can inform the development of support programmes for TD siblings and social skills training for HFA children. Overall, the results of the studies included in this thesis provide evidence that deficits in inhibitory control moderate the relationship between relatively intact social knowledge and impaired social competence in HFA children. This refinement of the executive dysfunction account is a useful building block for an improved multiple-deficit model of the autism phenotype.

This thesis examines the effectiveness of social problem solving programmes and the efficacy of an assessment tool designed for mentally disordered offenders (MDOs) and intellectually disabled (ID) offenders in secure hospital settings. Firstly, a systematic review concluded that all studies reported benefits of the social problem solving programmes with MDOs. Several studies also identified that shorter revised programmes had lower drop-out rates, and were more cost-effective. Methodological limitations were identified and suggested further research is needed. Secondly, Interpretative Phenomenological Analysis (IPA) was utilised to explore the meanings ID offenders in a secure hospital attribute to their experience of the Thinking Skills Offender Programme (TSOP). Five themes emerged and participants’ conveyed a sense of hope in relation to their treatment, discussed challenges they faced, identified the impact the TSOP had on factors contributing to their offending behaviour, and wanted to share their experiences with a wider audience. Further research to develop effective programmes for ID offenders is discussed. Thirdly, an assessment and treatment of an adult male violent offender with ID and Autistic Spectrum Disorder (ASD) who undertook the TSOP in a medium secure unit is examined. The findings highlighted the difficulties in assessing and treating such patients using conventional methods and the need for standardised assessments and interventions for this population is discussed. Finally, the reliability and validity of the Novaco Anger Scale and Provocation Inventory (NAS-PI) is examined with MDOs and ID offenders. Its clinical utility in inpatients settings and limitations are also discussed. This thesis has highlighted the benefits of social problem solving programmes with MDOs and ID offenders, difficulties of conducting research with this population, and the need for further rigorous research into assessments and interventions.

Introduction The number of prescriptions dispensed for opioid medicines has increased in the U.K. in the last two decades and studies have shown patients are receiving opioids for longer periods than in the past. There is a lack of evidence as to the effectiveness of these drugs when used long-term, as efficacy evidence is taken from short clinical trials in populations who do not have the comorbidities commonly seen in chronic pain patients. Large observational studies of patients prescribed opioid medicines outside of clinical trials, have identified that some patients taking long-term opioids are reporting they are still in high levels of pain. There is also a concern that patients are receiving high dosages of opioid medicines without effective pain relief. However, no studies in the U.K. have looked at the proportion of patients who continue to receive opioids (for all conditions) in the long-term or at high dosages so we do not know how opioid use develops in the U.K. Research from other countries has also identified that long-term and high dose use is linked to patient characteristics such as patient demographics and psychological and physical comorbidities. For example, a prior history of depression has been found to increase the risk of long-term and high dose use. This is of concern as this may indicate that patients may be potentially medicating the depression with the opioid. This may not be the case in the U.K. due to key factors such as the structure of the health system, so the aim of this thesis was to see if this phenomenon could potentially be occurring in the U.K. Methods This thesis was a retrospective observational cohort study of patients receiving opioid medicines for non-cancer conditions using data from a U.K. derived primary care database, the clinical practice research datalink (CPRD). Patients were included in the study if they received a prescription for opioid medication at any point in the year 2009 and followed, where possible to January 2015 (though data was collected for baseline variables prior to 2009). This thesis consists of a series of longitudinal analyses that attempt to define and describe the probability of long-term use and proportion of patients who receive high dosages in the U.K and seeks to understand how baseline characteristics (such as having a comorbid condition occurring before opioid use starts) affect the probability of long-term and high dose use. Competing risks methods were used to calculate the probability of continuation of opioid medicines (using death as a competing risk) and to determine long-term use. Cox regression models were used to determine whether baseline factors (such as prior antidepressant use) were associated with discontinuation of long-term use. Calculation of odds ratios were used to predict whether baseline characteristics predicted high dose use. Cox regression was also used to predict time to discontinuation of high dose use. Results In the U.K., 10.58% of patients received opioid medicines to treat non-cancer pain in the year 2009. Of the non-cancer patients included in the study, 41.41% were patients who received opioids in the six months prior to 2009 and the remaining were new users of opioid medicines. In the new user opioid group, 5.75% continued to be prescribed opioids for at least one year. When including new and existing users of opioid medicines, one in thirty people in the U.K. population who started opioids for non-cancer pain in 2009 were continuously prescribed opioids for a full year. Patients who were female, received an antidepressant before opioid use started and were in the youngest age category were more likely to continue opioid use past 2 years. The probability of continuing to take opioid medicines is higher in patients who have been receiving opioids for longer and are on higher dosages; in patients who had received over 10mg OMEQ for over two years, over half of patients continued to receive prescriptions for opioid medicines for the five year period study after 2009. In the U.K. population, one in a hundred opioid medicine users were prescribed a high dose (estimated dosage received >120mg oral morphine equivalents per day for at least 91 days) for non-cancer pain in their first 91 days of use in the year 2009. Patients receiving high dosages were likely to be receiving multiple opioid drug types and to receive preparations with multiple release profiles. In new users of opioid medication, the odds of high dose use were increased in patients who were younger (aged 18-49 years), had 3 or more comorbidities or were in receipt of an antidepressant or benzodiazepine and/or anti-anxiety drug before or after opioid use started. In new and existing users of opioid medicines, patients who were receiving high dosages were more likely to be diagnosed or be recorded with symptoms of depression or anxiety and to have been prescribed an antidepressant or benzodiazepine and/or other anti-anxiety drug in the youngest age group compared to the older age groups. Of the patients that were prescribed high dosages of opioid medicines for at least 91 days, 37.64% of patients did not have a second consecutive high dose quarter due to death or stopping high dose use. Almost one in five patients who had a high dose quarter continued to have a high dose for the next three years (22.98%). Older patients, patients prescribed weak opioids and/or tramadol discontinued high dose use at a faster rate than younger patients. Conclusion Both high dose and long-term use were found to be associated with a prior prescribing of antidepressants before opioid use started, suggesting that in the U.K. psychological comorbidities are associated with continued and high dose opioid use. Further work is required to measure outcomes within these groups and to understand the care that these patients have already received. Most patients who start opioid medicines in the U.K. stop taking them in their first year of use. However, of those who continue use past two years, a large proportion continue for the full five year period. Similarly, only a small proportion of patients receive high dosages of opioid medicines but once this use is established, many patients have a high probability of continuation. Further work should be undertaken to facilitate effective review of these patients in practice.

The proliferation of social media-based research on mental health offers exciting possibilities to complement traditional methods in mental health care. As ascertained by psychology experts, the online platform should get priority over offline as it offers considerably reliable diagnosis than granted in person. Early detection does not only alleviate the effects of depression on the patient but also benefits the whole community. In this thesis, we explore computational methods in tackling some of the research challenges in depression analysis and make four contributions to the body of knowledge. First, we develop a binary classification model for classifying depression-indicative text from social media. We propose three feature engineering strategies and assess the effectiveness of supervised model to enhance the classification performance in predicting posts indicate depression. To tackle the short and sparse social media data, we particularly integrate the coherent sentiment-topic extracted from the topic model. Additionally, we propose strategies to investigate the effectiveness of affective lexicon in the task of depression classification. Second, we propose a computational method for analysing potential causes of depression from text. With this study, we demonstrate the ability to employ the topic model to discover the potential factors that might lead to depression. We show the most prominent causes and how it evolved over time. Furthermore, we highlight some differences in causes triggered between two different groups, i.e. high-risk of depression and low-risk. Hence, this study significantly expands the ability to discover the potential factors that trigger depression, making it possible to increase the efficiency of depression treatment. Third, we develop a computational method for monitoring the psychotherapy outcome from the individual psychotherapy counselling. Third, we develop a computational method for monitoring the psychotherapy outcome from the individual psychotherapy counselling. By doing this, we show the possibilities of utilising the topic model to track the treatment progress of each patient by assessing the sentiment and topic discussed throughout the course of psychotherapy treatment. Fourth, we propose an unsupervised method called split over-training for identifying user's intention expressed in social media text. We develop a binary classification model for classifying intentions in texts. With this study, we want to show the possibility of applying the intention analysis in mental health domain. Overall, we demonstrate how computational analysis can be fully utilised to benefit clinical settings in mental health analysis. We suggest that more future work could be further explored to complement the traditional settings in mental health care.