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<p>This thesis presents research documenting the effectiveness of computer-assisted cognitive remediation for patients with mood disorders. The first chapter provides an overview of cognitive impairment in patients with bipolar disorder (BD) and major depressive disorder (MDD), and a concise review of cognitive remediation in patients with schizophrenia, where the efficacy of these interventions has been reasonably well studied. The results of an analysis comparing neuropsychological test performance in patients with BD, MDD, and healthy controls is presented in Chapter 2, where we show a similar degree of deficit in both patient groups on processing speed, working memory, and mental flexibility tasks, and a greater degree of deficit in patients with BD on delayed recall and verbal fluency tasks. In Chapter 3 we present the results of our primary analysis examining the effectiveness of CACR for patients with BD and MDD; we show significant improvement on neuropsychological tests of working memory and delayed memory following remediation, and positive associations between improvement in neuropsychological test performance, and improvement in subjectively-rated cognitive and psychosocial functioning. Finally, in Chapter 4 we present functional neuroimaging evidence that shows increased activation following cognitive remediation in frontal control regions supporting working memory and in the right hippocampus supporting recollection memory. Although behavioural performance on the corresponding tasks was stable, the observation of increased activation in frontal and medial temporal brain regions following remediation is in line with our finding of improvement on neuropsychological tests of working memory and delayed recall post-training. Taken together, the results presented in this thesis provide convergent behavioural and neural evidence to demonstrate the efficacy of computer-assisted cognitive remediation for patients with mood disorders. These novel findings contribute to a growing body of literature that shows cognitive remediation to be an effective cognitive management strategy across a range of psychiatric and neurological disorders.</p> / Doctor of Philosophy (PhD)

While the physical health benefits of exercise are well established, mental health benefits remain unclear. The literature reports reduced stress and improved cognitive function in rodent exercise studies, and improved mood scores in humans. However, though mood disorders are characterized by poor response to treatment, studies rarely evaluate difficult-to-treat patients or functional outcomes. Therefore, we evaluated the impact of 12-week, group-based exercise programs (running or yoga) on mood and functional outcomes including health-related quality of life (HRQOL) and social and cognitive functioning. Methods: Study 1 was a retrospective review of mood and stress outcomes in participants with difficult-to-treat mood disorders. In Study 2, we measured functional outcomes before and after the running program in a subsample from Study 1. Improved friendship and high injury rates in the running group inspired Study 3, a randomized control trial to evaluate mood and functional outcomes in a non-clinical sample using yoga, a low-impact exercise program that included cognitive control. Results: In Study 1 (n=46), depression (p<0.0001) and stress (p=0.01) scores improved over time, and improved friendship levels were predictive of improved mood scores (p<0.04). In Study 2 (n=18), we found improved scores on several HRQOL subscales, including social functioning (p-values<0.01) and weak improvements in working memory and processing speed (p-values<0.04). In Study 3, yoga participants (n=20) had improved stress (p=0.02), loneliness (p=0.002), and HRQOL (p-values<0.03) scores, compared to wait-list controls (n=8). Yoga participants improved on tasks reflecting hippocampal memory (p-values<0.006) and attention and inhibitory control (p=0.03). Regression and mediation analyses suggest that social support mediates the stress-reducing impact of yoga (p-values<0.0005). Discussion: Group-based exercise programs impart benefits across mental health and functional outcomes for participants with and without mood disorders. Exercise may be an effective adjunctive treatment for mood disorders, and more data is needed on how social support impacts clinical outcomes. / Thesis / Doctor of Philosophy (PhD) / This dissertation examines the impact of exercise across multiple indications of mental health and functioning including mood scores, stress, cognitive function, social function and health-related quality of life (HRQOL) in participants with and without mood disorders. Youth and adults engaged in 12-week group-based exercise interventions of running or yoga and completed comprehensive mental health and neurocognitive assessments. Results: Participation in a structured exercise program was associated with improved stress and depression, social functioning, physical and mental HRQOL domains and limited improvements in cognitive function. Results also support therapeutic benefits of structured high- and low-intensity exercise programs across multiple symptoms in patients with difficult-to-treat mood disorders, and further suggest that reduced stress and increased social functioning play key roles in the mental health benefits observed. These results represent a new standard for mood disorders research, to better understand the how lifestyle strategies are effective for the treatment of mental illness.

Introduction: In Major Depressive (MDD) and Bipolar Disorders (BD), there are well-documented changes in sleep and biological rhythms. However, how sleep and biological rhythm disruptions impact functioning and quality of life (QOL) in these populations, and how these disruptions affect perinatal mood and anxiety remains little-known. In this thesis, we aimed to compare sleep and biological rhythms in individuals with and without mood disorders, and to investigate whether these measures can account for worsened functional impairment and QOL in these populations. We investigated whether clinical variables combined with sleep and biological rhythms during pregnancy can be used to predict depressive and anxiety symptom severity postpartum. Finally, we investigated longitudinal changes in sleep, and biological rhythms over the perinatal period. Results: Subjective and objective sleep and biological rhythm disruptions, and light exposure differences are wide-spread in MDD and BD. Regression analyses showed that subjective and objective sleep and biological rhythm disruptions can explain 43% of variance in QOL scores, and 52% of variance in functional impairment in MDD, BD and healthy controls. Clinical and demographic variables, objective and subjective sleep and biological rhythm measures collected during pregnancy accounted for 50% of postpartum depression and 49% of postpartum anxiety symptom severity variance, in regression analyses. Numerous sleep and biological rhythm changes occurred across multiple domains from pregnancy to postpartum. Conclusion: Results suggest that sleep and biological rhythm disruptions occur across many domains in mood disorders, including sleep, light exposure, daily activity rhythms and melatonin. These disruptions are associated with worse QOL and functioning in BD, MDD and healthy controls. Biological rhythms and sleep changes across the perinatal period can be used to predict severity of postpartum depressive and anxiety symptoms. This work highlights the importance of sleep and biological rhythms as intervention targets across different outcomes, and across different mood diagnoses. / Thesis / Doctor of Philosophy (PhD) / Sleep and biological rhythms are often disrupted in individuals with depression and bipolar disorder. In this thesis, we aimed to compare sleep and biological rhythms in individuals with depression or bipolar disorder, against individuals without these disorders. We investigated whether sleep and biological rhythms contribute to functioning and quality of life in these individuals. As sleep and biological rhythms are disrupted in pregnancy and following childbirth, we assessed whether sleep and biological rhythms during pregnancy can be used to predict postpartum depression and anxiety severity. Finally, we investigated changes in sleep, biological rhythms and light exposure from pregnancy to postpartum. Results indicate that disruptions in sleep, biological rhythms, and changes in light exposure are widespread in mood disorders. These disruptions are linked to worse quality of life and functioning. Sleep and biological rhythms change from pregnancy to postpartum, and can be used to predict severity of postpartum depression and anxiety.