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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.

The objective of this thesis was to determine the association between exposure to parental BD during childhood and risk of mood disorder. Offspring of one parent with BD completed annual clinical assessments as part of a 16-year prospective cohort study. Clinical data in the parents from Ottawa and Halifax were mapped onto the first decade of their offspring’s life to estimate the timing, duration and severity of exposure to their illness. The duration of parental BD was associated with a 2 to 2.5 fold increased risk of any psychopathology (HR: 1.9, 95%CI: 1.0-4.0), and unipolar depression (HR: 2.6, 95%CI: 0.9-7.5), and a 7 fold increased risk of substance use disorders (HR: 7.1, 95%CI: 1.8-37.0). A longer duration of exposure to parental BD may be an important indicator of mood and non-mood psychopathology risk in offspring. This has implications for early intervention and preventive efforts in high-risk youth.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Nos transtornos de humor, o estigma internalizado (internalização de estereótipos depreciativos associados a uma condição) é desafiador e prejudicial para a reabilitação e qualidade de vida do indivíduo. O presente estudo tem como objetivo investigar o estigma internalizado e as associações entre essa variável e as variáveis sociodemográficas e clínicas, além da esperança e adesão ao tratamento entre pessoas com transtornos de humor. Este estudo com abordagem quantitativa foi realizado com uma amostra de conveniência de 108 pacientes com transtornos de humor, em tratamento em um Centro de Atenção Psicossocial no interior de São Paulo - Brasil. Na coleta de dados foram aplicados os instrumentos: ISMIBR para investigar o estigma internalizado; MAT para investigar a adesão ao tratamento, EEH para analisar a esperança; aplicação da BPRS-a para observar a sintomatologia dos pacientes, e um questionário com questões sociodemográficas e clínicas. Na análise de dados foram empregados testes de comparação de média, teste de correlação e regressão linear múltiplo. Neste estudo predominam mulheres, sem ensino superior, sem companheiro, sem trabalho. A maioria tinha transtorno afetivo bipolar, era aderente ao tratamento medicamentoso, referiu internações psiquiátricas e tentativas prévias de suicídio e negou episódios de heteroagressão. Na amostra investigada, maiores níveis de estigma estiveram associados à maior sintomatologia, menor nível de esperança, tentativas prévias de suicídio, histórico de comportamento agressivo, internações psiquiátricas, não adesão ao tratamento e não ter trabalho. No modelo de regressão linear múltiplo estiveram associadas ao estigma as variáveis trabalho, tentativas de suicídio, sintomas e esperança. Nesse estudo foram identificados fatores que podem conferir ao indivíduo maior vulnerabilidade ao estigma internalizado e que precisam ser cuidadosamente investigados e abordados em intervenções voltadas para a redução do estigma e à reabilitação psicossocial / In mood disorders, the internalized stigma (internalization of derogatory stereotypes associated with a condition) is challenging and detrimental to the individual\'s rehabilitation and quality of life. The present study aimed to investigate the internalized stigma and the associations between these variables and sociodemographic, clinical variables, as well as hope and adherence to treatment among people with mood disorders. This quantitative approach was carried out with a convenience sample of 108 patients with mood disorders undergoing treatment at a Psychosocial Care Center in the interior of São Paulo - Brazil. In the data collection, the following instruments were applied: ISMI-BR to investigate internalized stigma; MAT to check adherence to treatment, EEH to examine the hope and application of BPRS-a to observe patient\'s symptomatology and a questionnaire with sociodemographic and clinical issues. In the data analysis, mean comparison, correlation test, and multiple linear regression tests were used. In this study, women predominated, without higher education, without a partner, without work. Most of them presented bipolar affective disorder, adhered to drug treatment, reported psychiatric hospitalizations and previous suicide attempts, and denied episodes of heteroaggression. In the sample investigated, higher levels of stigma were associated with greater symptomatology, lower level of hope, previous attempts of suicide, history of aggressive behavior, psychiatric hospitalizations, non-adherence to treatment and not having a job. In the multiple linear regression model, the variables labor, suicide attempts, symptoms, and hope were associated with the stigma. In this paper, were identified factors that may give the individual greater vulnerability to internalized stigma and which need to be carefully investigated and addressed in interventions or aiming at reducing stigma and psychosocial rehabilitation

A atividade física é considerada uma prática que traz benefícios para o corpo e a mente. Entretanto, se por um lado há evidências de que exercício físico moderado pode ajudar a saúde mental, também existem relatos de alterações de humor com características depressivas associadas ao treinamento de atletas de elite, podendo culminar com o aparecimento da chamada “síndrome de overtraining". Este trabalho procurou avaliar estas alterações de humor associadas a atividade física intensa, focando-se em três pontos: 1) caracterização de suas manifestações psicológicas, 2) avaliação da especificidade da associação e 3) verificação da possibilidade de alguma vulnerabilidade constitucional influenciar as alterações. Os sujeitos se dividiram em três grupos: atletas (N = 56, 30 homens – 26 mulheres; idade média = 18,16 anos), vestibulandos (222, 120 – 102; 17,48) e universitários (446, 259 – 187; 22,08). Instrumentos de avaliação de humor (POMS e PANAS-X) foram aplicados em atletas e vestibulandos em três oportunidades, ao longo da preparação para a competição mais importante da temporada ou o vestibular. Universitários, submetidos a estresse físico e intelectual estável e relativamente menor, foram avaliados apenas uma vez. Foram estudadas as variações de estados afetivos de cada grupo e suas relações com a quantidade de treinamento / estudo e a proximidade da competição / vestibular. O grupo de atletas e uma amostra de vestibulandos, definida randomicamente, foram avaliados com um instrumento de diagnóstico psiquiátrico (SCAN). Foi estudado, utilizando-se sintomatologia psiquiátrica prévia ou “afeto negativo traço" como marcadores, se fatores de vulnerabilidade exerceram algum tipo de influência sobre as alterações de humor em estudo. Os resultados foram avaliados segundo os três grupos de sintomas de um modelo tripartide de ansiedade e depressão: 1) um fator geral de afeto negativo, que inclui sintomas não específicos; 2) um grupo de sintomas relativamente específicos de depressão, o qual reflete falta de experiências emocionais positivas (chamado de afeto positivo), e 3) um grupo de sintomas relativamente específicos de ansiedade, o qual reflete manifestações de tensão somática. Foram encontradas alterações de humor entre os atletas. Suas características principais foram: aumento de fadiga, diminuição de afeto positivo e nenhuma alteração de afeto negativo (o que indica proximidade com o construto de depressão); associação com a quantidade e a intensidade de treinamento, mas não com a proximidade da competição; nenhuma influência de fatores de vulnerabilidade. Os vestibulandos também apresentaram alterações de humor, mas com características diferentes: aumento de fadiga, aumento do afeto negativo e nenhuma alteração do afeto positivo (o que indica proximidade com o construto de ansiedade); associação com a proximidade do vestibular (a associação com a quantidade de estudo não foi conclusiva); tendência de que fatores de vulnerabilidade ligados a sintomatologia psiquiátrica prévia influenciem sua intensidade. Esses resultados apontam para a especificidade da associação entre as alterações de humor encontradas entre os atletas e a atividade física intensa a qual se submetem. / Physical activity is considered to be beneficial to both body and mind and evidences that moderate intensity exercise can improve mental health are increasing. Nevertheless, there are also evidences that depressive mood alterations are associated with elite athletes training and that this training can lead to the so called “overtraining syndrome". This work aimed to evaluate these mood alterations associated with intense physical activity considering three points: 1) characterization of its psychological manifestations, 2) association specificity, and 3) influence of some kind of constitutional vulnerability. Subjects were athletes (N = 56, 30 men – 26 women; mean age = 18,16 years), last year high school students (222, 120 – 102; 17,48) and college students (446, 259 – 187; 22,08). Athletes and high school students were evaluated with psychometric instruments (POMS and PANAS-X) three times during the preparation for the most important competition of the season or for the “vestibular" (Brazilian exam to enter college). College students, submitted to stable and relatively lower levels of physical and intellectual demands, were evaluated only once. Mood states fluctuations and their relation to training volume / hours of study and proximity to competition / “vestibular" were studied. The athletes and part of the high school students, randomly selected, were also evaluated with a psychiatric diagnostic instrument (SCAN). The influence of vulnerability factors over the mood alterations were studied, using previous psychiatric symptomatology or negative affect trait as markers. Results were evaluated according to the three groups of symptoms from a tripartite model of anxiety and depression: 1) a general negative affect factor, which includes nonspecific symptoms; 2) a relatively specific depression cluster of symptoms that reflects the absence of positive emotional experiences (called positive affect); and 3) a relatively specific anxiety cluster of symptoms that reflects the manifestations of somatic tension. Mood alterations were found among the athletes. Presence of fatigue, diminished positive affect and no alteration in negative affect (which points to proximity to the depression construct); association with training volume and intensity, but not with competition proximity; and no vulnerability factors (related to psychiatric history, trait negative affect and profile of affective traits) influence were the athlete mood alterations characteristics. The high school students showed mood alterations too, but with different characteristics: fatigue, increased negative affect and no alteration in positive affect (which points to proximity to the anxiety construct); association with “vestibular" proximity (the association with study volume was non conclusive); and a tendency that vulnerability factors (related to psychiatric history) influences their intensity. Results point to the specificity of the association between the athletes’ mood alterations and the intense physical activity performed by them.

Na literatura encontramos trabalhos que revelam que em indivíduos tratados com antipsicóticos e antidepressivos há um aumento de cáries, gengivite, periodontite e estomatites. No entanto, além dessas propriedades anticolinérgicas, sabidamente as drogas antipsicóticas e, em menor intensidade, as drogas antidepressivas provocam ações no sistema muscular como um todo. O uso de drogas antipsicóticas é reconhecidamente associado com efeitos colaterais motores agudos e crônicos, como parkinsonismo, acatisia e discinesia tardia. Medicações antidepressivas, tanto as clássicas tricíclicas, quanto as de nova geração, como os inibidores seletivos de recapitulação de serotonina têm sido apontadas como causadoras de efeitos musculares colaterais semelhantes aos antipsicóticos. Tendo em vista o exposto, o objetivo deste trabalho foi analisar eletromiograficamente os músculos masseter e temporal, a força de mordida e a eficiência mastigatória em indivíduos tratados com antipsicóticos e antidepressivos, mais precisamente, pacientes com esquizofrenia e transtornos do humor, e comparar com o grupo controle, dada a importância destas funções dentro das ações do sistema estomatognático. / In the literature we found studies showing that individuals treated with antipsychotics and antidepressants are an increase of caries, gingivitis, periodontitis and stomatitis. However, besides these anticholinergic properties, known antipsychotic drugs, and less intensity, antidepressant drugs cause muscle actions in the system as a whole. The use of antipsychotic drugs is known to be associated with side effects engines acute and chronic conditions such as parkinsonism, akathisia and tardive dyskinesia. Antidepressant medications, tricyclic both classical, as the new generation, such as selective inhibitors of recapitulation of serotonin have been identified as causing muscle side effects similar to antipsychotics. Given the above, the objective was to analyze the electromyographically masseter and temporal muscles, bite force and masticatory efficiency in patients treated with antipsychotics and antidepressants, specifically, patients with esquizofrina and mood disorders, and compare with the group control, given the importance of these functions within the actions of the stomatognathic system.