Mood disorders (major depressive and bipolar spectrum disorders) have devastating effects on quality of life, with individuals who do not respond to pharmacological interventions showing a greater risk of impaired functioning, suicidality, and symptom relapse. Electroconvulsive therapy (ECT) has demonstrated consistent efficacy for treating mood disorders. However, there is a relative paucity of research examining the effectiveness of ECT in ambulatory settings and for patients who present with psychiatric comorbidities. This thesis sought to characterize the clinical, functional, and neuropsychological profile and outcomes (i.e., effectiveness and side effects) of a mixed mood disorders population undergoing ambulatory ECT with minimal research-related restrictions. In study one, we demonstrated that ambulatory ECT patients were clinically severe and complex, with frequent psychiatric multimorbidity, high symptom severity, and elevated functional impairment. ECT was effective at significantly reducing depressive symptoms in the short- and long-term; yet the rates of remission and response were lower than expected. In study two, we found that objective cognitive functioning remained largely unchanged following ECT, a finding that should be interpreted with caution given the use of a brief cognitive screening battery. Interestingly, whereas patients who responded to ECT reported a lessening of subjective memory complaints, those who did not respond showed an increase in memory complaints post-ECT. In study 3, we sought to identify clinical and cognitive predictors of ECT outcomes using machine learning methods; we were unable to predict remission status, response status, or percent change in depressive symptoms in our sample. Overall, this thesis advances our understanding of the clinical, cognitive, and functional characteristics and outcomes of ambulatory ECT delivered under naturalistic conditions. This work highlights the importance of considering clinical comorbidities and cognitive functioning in ECT research and delivery and encourages a collaborative approach to clinical care aimed at enhancing treatment of patients with severe mental illness. / Dissertation / Doctor of Philosophy (PhD) / Severe mood disorders, such as depression and bipolar disorder, are associated with significant difficulties in social, occupational, and personal functioning. Electroconvulsive therapy (ECT) has shown consistent efficacy in reducing depressive symptoms, even in patients who did not respond to pharmacotherapy. This thesis advances our understanding of the therapeutic and adverse side effects of ECT in two understudied areas, ECT delivered in an outpatient setting and under naturalistic conditions with minimal research-related restrictions. We found that patients undergoing ECT were clinically complex and severe. ECT was effective at reducing depressive symptoms, but remission and response rates were lower than expected. Although, cognitive functioning, following ECT, remained largely unchanged on a brief screening assessment that may have underestimated cognitive changes, patients continued to report memory concerns. This thesis highlights the importance of considering patients’ full clinical and cognitive presentation in ECT research and delivery and encourages a collaborative approach to clinical care to better treat patients with severe mental illness.

Cognitive theories propose that interpretive biases play an important role in the onset and maintenance of emotional disorders. To investigate the proposed causal role of interpretive biases, this study examined if it is possible to train interpretations of ambiguous situations, and if this training affects emotional vulnerability and memory. The results indicated that the interpretive training was effective in inducing the intended group differences in interpretive bias, but that the positive training was more effective than negative training. These findings also highlight the potential benefits of inducing positive interpretive biases on mood and emotional vulnerability for some individuals (i.e., individuals with high depression or rumination scores). Additionally, results from the current study demonstrate that manipulating interpretive biases can result in corresponding changes in memory. In sum, findings from the current study hold valuable implications for the effects of positively manipulating interpretive biases on mood, emotional vulnerability, and memory. Future research can further elucidate the relationship between interpretive biases and mood, as well as extend current findings to a clinical population.

Background and objectives: Information and communication technologies (ICTs) have been in use in the health setting since the time of the first telephones. However, the advent of computers, personal-computers (PCs) and, more recently, mobile information and communication technologies (mICTs) such as mobile phones, smartphones, tablet-pcs and laptops, has seen technology become increasingly integrated into how care is delivered and received. No research has yet explored how people with mood disorders use mICTs in their everyday lives and, more specifically, how they might use mICTs to look after themselves. This oversight has led to technology redundancy and high attrition rates in the use of this type of technology. Further research was therefore required to understand the meaning that this type of technology holds for people with mood disorders. This qualitative study aimed to explore the views and experiences of people with mood disorders, and their mental health and social care professionals, in using mICTs. Design and methods: A meta-synthesis was completed, guided by the work of Sandelowski and Barroso, using thematic synthesis an approach, as designed by Thomas and Harden. An exploratory qualitative approach, using in-depth, semi-structured interviews with 26 patients with mood disorders in secondary and specialist mental health services, and ten mental health and social care professionals, was subsequently employed. Participants’ datasets were analysed using Constructivist Grounded Theory (CGT). Grounded theory (GT) involves the gradual identification and integration of categories of meaning from the data, and the identification of relationships between them. Results: The rigorous and systematic nature of the meta-synthesis identified shortcomings in current research and clearly identified a gap in the research literature regarding mICTs and mood disorders. The in-depth primary study created a theory explaining how mobile technology was used in daily life, and also, more specifically, how it was used to manage recovery from mood disorders. The core category and participants’ main concern that emerged from the data, forming theory, was ‘Centrality; through praxis of interconnectivity’. Patients with mood disorders used their mICTs to stay central within their on-and-offline worlds and held them central in their importance of attachment. Health and social care professionals worked around their provision of basic mICTs and lack of informational support when using them with their patients. Centrality was achieved through the ‘Praxis of interconnectivity’; the act of managing their connectedness using mICTs. This interconnectivity was not fixed; instead, it offered fluidity for participants to manage their continuums of use through their ‘Outsourcing of needs’, ‘Management of needs’, and ‘Disconnection of needs’. Conclusions and future implications: This study refocused the attention of ICT research onto arguably the most important person, the end-user, and, in this instance, the people recovering from mood disorders, and their health and social care professionals. The CGT provided, for the first time, a theory that explained how people made use of their mICTs. Additional research is warranted to further understand the transferability of the theory to other client groups, and, in so doing, whether it can be transformed into a formal theory. Also, further research is recommended to translate the theory into practical tools for clinicians; for example, the creation of an mICT self-management questionnaire or a digital hygiene support package. Both patients recovering from mood disorders, and health and social care professionals, can utilise the findings of this study to help make sense of their mICT use. The study findings can also help inform and encourage the further incorporation of mICTs into the health and social care settings; spanning the therapeutic to systemic levels so that the full potential of these ubiquitous technologies can be harnessed to improve care and care delivery.

Thesis (M.Ost.)--Unitec New Zealand, 2008. / Includes bibliographical references (leaves 77-86).

Abstract Depression is a common consequence of stroke and it is known to be associated with deterioration of quality of life. However, only limited information is available on the relationships between depression and communicative and cognitive disorders. Moreover, the present knowledge of the determinants of the domains of quality of life is limited, and little is known of e.g. the changes in sexual behaviour of stroke patients and their spouses. This prospective study was carried out to evaluate the prevalence of post-stroke depression and aphasia and to study their interrelationships and neuropsychological and functional correlates. The particular aim of the study was to investigate the domain-specific quality of life, and to assess its clinical and sociodemographic correlates, and to study the impact of stroke on the sexual functions of stroke patients and their spouses. The study consisted of 156 first-ever stroke patients. Depression was diagnosed in 53% of the patients at 3 months and in 42% of the patients at 12 months post-stroke according to DSM-III-R-criteria. One third of the patients were aphasic, 70% of them at 3 months and 62% at 12 months after stroke suffering from depression. Among the aphasic patients the prevalence of major depression increased from 11% to 33% during the 12 months follow-up. There was an association between post-stroke depression and cognitive impairment, the domains most likely to be defective being memory, non-verbal problem solving, and attention and psychomotor speed. The non-verbal neuropsychological test performance in the aphasic patients was significantly inferior to that of the patients with dominant hemisphere lesion without aphasia. The quality of life of the patients was low at 3 months after the stroke, and it did not improve during the follow-up of a year. The test domains most often impaired were Physical functioning, Physical role limitations, Vitality and General health. Depression, although mostly minor, and being married emerged as significant independent contributors to low score value of Vitality and Physical role limitations. All the analyzed aspects of sexuality were commonly decreased as a consequence of stroke both in the patients and their spouses. Nocturnal erections were impaired in 21 (55%) of the male patients. The present results demonstrate that more than half of the patients after stroke suffer from depression and the frequency of major depression seems to increase over time, especially among the aphasic patients. Both depression and aphasia increase the liability of cognitive deficits. Stroke affects various dimensions of quality of life extensively, and the most important determinants entailing low quality of life seem to be depression, and, interestingly, being married. As a part of quality of life, sexual function and satisfaction with sexual life are impaired both in stroke patients and spouses. These findings call for multidimensional evaluation of stroke patients and provide new challenges for stroke rehabilitation.

Depression is associated with reduced declarative memory performance and decreased hippocampal volume. Depression has also been associated with decreased levels of adult neurogenesis in the dentate gyrus. Computational models propose that neurogenesis is critical for the computational process of pattern separation, whereby distinct memory representations are created for very similar stimuli and events. It has been proposed that depression negatively impacts pattern separation abilities; however, a link between depression and performance in pattern separation memory tasks has yet to be investigated. Accordingly, we designed a study to investigate the relationship between pattern separation performance and the severity of depression symptoms. Participants completed a recognition memory test with high pattern separation demands as well as a set of questionnaires to gauge their level of depression. We found a negative relationship between depression scores and pattern separation scores in support of the theory that depression is negatively related to pattern separation performance.

No description available.

Thesis advisor: Ce Shen / A compelling body of literature suggests that negative appraisal may be associated with adverse reactions to traumatic stress (Ehlers & Clark, 2000). However, very few studies have examined how cognitive appraisal influences posttraumatic adaptation in people with serious mental illness (SMI) despite evidence of disproportionately high prevalence rates of trauma exposure and Posttraumatic Stress Disorder (PTSD) in this population. The major purpose of this study was to examine the relationship between negative appraisal and PTSD symptoms among adults diagnosed with SMI. It was hypothesized that negative appraisal would have a positive and significant association with traumatic stress symptoms in a clinical sample of community clients diagnosed with major mood and schizophrenia-spectrum disorders when controlling for gender, total lifetime trauma, substance use, and severity of symptoms associated with SMI. Multiple regression was employed to conduct a secondary analysis of clinical data from 291 community support clients who were receiving services from three community mental health centers in the state of Rhode Island during March to September 2009. Results supported the main hypotheses that all three types of negative appraisal with respect to self, world /others, and self blame as well as overall appraisal were positively and significantly associated with PTSD symptoms. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Social Work. / Discipline: Social Work.

The neurocognitive model of antidepressant treatment action states that antidepressants work by producing relatively immediate positive shifts in emotional processing, which translate into clinical improvement with time. Short-term or even acute doses of antidepressants can, for example, increase memory for positive self-referent words or decrease amygdala activation to fearful faces, and these early changes correlate with later clinical improvement. However, there are a number of ways in which the model needs further probing. The aim of this thesis was to test the neurocognitive model by: 1) investigating whether changes in emotional processing occur in an antidepressant with a novel mechanism of action, St John's wort, as the model predicts; and 2) examining whether there is a comparable pattern of neuropsychological changes to citalopram in a population of high neurotic volunteers, whose baseline emotional biases may make them a more ideal group in which to study drug effects. We found that seven days of St John's wort produced similar changes to other antidepressants, for example reducing recognition of disgusted faces and attention to fearful faces while increasing memory for positive words. The drug did not affect other aspects of cognition including working memory and reward learning. These findings support the theory that early psychological changes are a common feature of all antidepressants. On the other hand, four weeks of citalopram treatment produced apparently contradictory effects in high neurotics, increasing memory for positive words but also increasing recognition of negative facial expressions. Neuroimaging data showed that high neurotics had greater response to neutral faces in emotional processing areas compared to low neurotics, which was reduced with citalopram. High neurotics also showed increased resting state connectivity in default mode network areas and between amygdala and cortical areas, which was again reduced with citalopram. We suggest that in this group citalopram corrects general negative emotional processing biases, but also works to decrease a natural aversion to particularly threatening socially-relevant stimuli. Overall this thesis supports the idea that early changes in emotional processing are vital for antidepressant action, but also suggests that in certain groups such as high neurotics, some changes may be more nuanced than previously reported and warrant further scrutiny.

Epigenetics continues to be redefined and new discoveries are likely to revolutionise the field still further. This thesis explores different aspects of how epigenetic regulation of gene expression contributes to human disease. Paper I explores the function of the IKKα kinase in regulating gene expression through the nuclear retinoic acid receptor (RAR). We define a set of genes requiring IKKα for their expression and found recruitment of IKKα to the RAR dependent on structural motifs in its protein sequence. This interplay between the NFκB pathway and nuclear receptor regulated transcription is important to consider when designing therapeutic strategies. Papers II and III focus on the plasma cell malignancy multiple myeloma (MM) and define a gene regulatory circuit defining an underexpressed gene profile in MM dependent on the Polycomb proteins. We provide proof-of-principle that the use of small chemical inhibitors may be operational in reactivating genes silenced by H3K27me3 and that this leads to decreased tumour load and increased survival in the 5T33 in vivo model of MM. We explored the genome-wide distribution of H3K27me3 and H3K4me3, and defined their association with gene expression in freshly-isolated malignant plasma cells from MM patients. Importantly, H3K27me3-marked genes in MM associated with more aggressive stages of the disease and less favourable survival. We present evidence that gene targeting by H3K27me3 is likely to not only involve a small population of tumour cells, but rather represent a common MM profile and further provide a rationale for evaluating epigenetic therapeutics in MM. Paper IV shows that pro-inflammatory gene expression in monocytes of psychiatric patients can be induced in vitro by sodium pump inhibitors, as the steroid hormone ouabain. We suggest that the ouabain-induced gene expression is regulated by an intricate network involving microRNAs, Polycomb and the H3K27me3 demethylase JMJD3. Our data indicates that epigenetic regulators play a role in transmitting cues between intrinsic and/extrinsic stimuli and gene expression in psychiatric illness. This thesis provides novel insights on how seemingly unrelated pathways may converge on transcriptional regulation and evidence that epigenetic modifiers contribute to the pathogenesis of human complex diseases such as multiple myeloma and mood disorders.