Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 5 uppsatser.

Introdução: As psicoses funcionais são transtornos psiquiátricos cuja principal característica é a perda da capacidade de julgar apropriadamente a realidade em decorrência de alterações na esfera do pensamento, percepção, emoção, movimento e comportamento. A esquizofrenia é o principal destes quadros, com curso crônico e/ou deteriorativo nas esferas social e ocupacional, gerando enormes custos pessoais e financeiros para os pacientes e cuidadores em todo o mundo. Estudos prévios têm mostrado a existência de prejuízos cognitivos em pacientes com transtornos psicóticos já no início da doença, sendo estes mais graves na esquizofrenia. Há evidências de que estes prejuízos são tanto inerentes aos próprios processos da doença quanto secundários ao tratamento. O presente estudo procurou caracterizar o perfil cognitivo de pacientes com psicoses de início recente (n=56), até 3 anos após o primeiro contato com serviços de saúde mental, sendo 34 com esquizofrenia e 22 com psicoses afetivas. Tais grupos de pacientes tiveram seu desempenho cognitivo comparado com o de um grupo controles saudável (n=70), recrutados a partir das mesmas áreas geográficas de São Paulo, Brasil. Até o momento, a maioria dos estudos foi realizada em países em desenvolvimento. Metodologia: A investigação utilizou ampla bateria de testes neuropsicológicos composta por 12 testes agrupados em 8 domínios cognitivos destinados a avaliar respectivamente amplitude atencional, velocidade de processamento da informação, memória verbal, memória visual, memória de trabalho, fluência verbal, funções executivas e funcionamento intelectual. O nível de significância foi de p < 0.05. Resultados: O desempenho do grupo de pacientes com psicoses foi pior do que o dos controles em todas as tarefas cognitivas, com diferenças estatisticamente significativas nas tarefas de velocidade de processamento da informação, memória verbal, fluência verbal e funcionamento intelectual, sendo os déficits mais graves no domínio da memória verbal (p < 0.001). Os grupos esquizofrenia e psicoses afetivas não diferiram significativamente quando comparados entre si. A inclusão do grupo controle na comparação mostrou que os pacientes com esquizofrenia tiveram desempenho significativamente pior do que os controles, o que não ocorreu entre os controles e as psicoses afetivas. A investigação da influência das variáveis demográficas e clínicas mostrou que o desempenho cognitivo foi beneficiado pela escolaridade, na maioria das funções; a idade atual maior teve associação negativa com a memória visual e fluência verbal; gênero masculino teve correlação positiva com a memória de trabalho, tempo de latência para produção de resposta não-convencional, e negativa com a quantidade de erros frente à necessidade de controle de respostas impulsivas.O padrão de tratamento descontínuo beneficiou o desempenho em tarefas de memória verbal, e prejudicou o desempenho na tarefa de antecipação espacial. O abuso/dependência de substâncias não mostrou correlação com nenhuma tarefa, o que ocorreu na análise de regressão. O início do transtorno em idades mais precoces não mostrou prejudicar o desempenho dos pacientes na maioria das tarefas. O tempo de duração de psicose não tratada (duration of untreated psychosis, DUP) mostrou correlação negativa com o tempo de latência para respostas não-convencionais no grupo das psicoses, influenciando negativamente o desempenho nas tarefas de vocabulário, memória verbal imediata e tardia, e a quantidade de respostas impulsivas. No grupo da esquizofrenia, a maior DUP esteve associada a piores resultados nas tarefas de raciocínio não-verbal, memória verbal imediata e tardia, e quantidade de erros no teste de antecipação espacial. Os sintomas negativos influenciaram negativamente os resultados em várias provas, o que não ocorreu com os sintomas positivos. Conclusão: Pacientes com psicoses funcionais de início recente apresentaram prejuízos cognitivos evidentes em comparação aos controles saudáveis. Confirmou-se também a existência de funcionamento cognitivo semelhante entre amostras de países desenvolvidos e em desenvolvimento através de bateria cognitiva ampla. Os prejuízos cognitivos estenderam-se a várias funções, configurando tendência a perfil de déficits generalizados. Embora tenha havido tendência a maior gravidade de déficits no grupo da esquizofrenia, não encontramos diferenças significativas entre os subgrupos diagnósticos, confirmando a presença de déficits cognitivos nas psicoses de início recente, particularmente nas de natureza não-afetiva. / Background and Purpose: Functional psychoses are psychiatric disorders which have as their main characteristic a loss of the ability to properly judge the reality due to alterations of thought, perception, emotion, movement and behavior. The main psychotic disorder is schizophrenia, which usually as a chronic and / or deteriorating course in social and occupational relationships, generating enormous personal and financial costs for the patients and their caretakers all over the world. Previous studies have shown the presence of cognitive deficits in patients at the onset of psychoses, more severely in schizophrenia. There are evidences that those deficits are both related to disease processes and to treatment effects. The present work sought to characterize the neuropsychological profile of patients with recent onset psychoses (n=56), up to 3 years after their first contact with Mental Health Service Care 34 with schizophrenia and 22 with affective psychoses. These patient groups had their results compared to a healthy control group (n=70) recruited from the same geographic area of São Paulo City, Brazil. So far, most studies of neuropsychological functioning in patients with recent onset psychoses have been conducted in high-income countries. Method: The cognitive assessment was conducted using a neuropsychological battery comprising 12 tests, grouped into 8 cognitive domains aimed at assessing respectively intellectual functioning, attentional span, information processing speed, verbal memory, visual memory, working memory, verbal fluency and executive functioning. The significance level was set at p < 0.05. Results: The performance of the psychosis group was worse than that of controls in all cognitive tasks, with statistically significant differences detected in information processing speed, verbal memory, verbal fluency and intellectual functioning tasks, most seriously in the verbal memory domain (p < 0.001). When compared against each other, the schizophrenia and affective psychoses subgroups were not significantly different. The inclusion of the control group in the analysis showed that patients with schizophrenia had significantly worse performance than controls, while such difference was not noticed when controls and affective psychoses groups were compared against. The influence of demographic variables and clinic data showed that cognitive performance was significantly associated with level of schooling in most cognitive tasks; visual memory and verbal fluency were negatively affected by age (deficit increased with age); male gender showed a positive relationship to executive memory and lag time for non-conventional answers, and a negative relationship to mistakes in impulsive answer control needs. Treatment discontinuity was related to better performance in tasks such as verbal memory, but with worse performance in the anticipation space test. Substance abuse or dependence did not influence significantly the performance in any of the tasks individually, but this occurred in the regression analysis. Earlier age of psychosis onset was non significantly related to performance of patients in any of the tasks. The duration of untreated psychoses (DUP) showed negative correlation with the lag time for non-conventional answers in the psychoses group, influencing the performance in tasks as vocabulary, immediate and delayed verbal memory, and the amount of impulsive responses negatively. In schizophrenia group, DUP was associated to worse results in non - verbal reasoning, immediate and late verbal memory, and error quantity in anticipation space test. Several activities were negatively influenced by negative symptoms, what did not occurred with positive symptoms. Conclusion: Patients with recent onset psychosis clearly display cognitive deficits when compared to healthy controls. The existence of similar cognitive functioning between samples studied in developed and developing countries was confirmed through wide cognitive test sets. Cognitive impairment was detected in multiple tasks, showing a widespread trend of deficit profiles. Although there was a tendency towards high severity deficits in the schizophrenia group, we could not find major differences amongst diagnoses subgroups. Our results reinforce the view that there are generalized cognitive deficits in association with recent-onset psychoses, particularly of non- affective nature.

Introdução: As psicoses funcionais são transtornos psiquiátricos cuja principal característica é a perda da capacidade de julgar apropriadamente a realidade em decorrência de alterações na esfera do pensamento, percepção, emoção, movimento e comportamento. A esquizofrenia é o principal destes quadros, com curso crônico e/ou deteriorativo nas esferas social e ocupacional, gerando enormes custos pessoais e financeiros para os pacientes e cuidadores em todo o mundo. Estudos prévios têm mostrado a existência de prejuízos cognitivos em pacientes com transtornos psicóticos já no início da doença, sendo estes mais graves na esquizofrenia. Há evidências de que estes prejuízos são tanto inerentes aos próprios processos da doença quanto secundários ao tratamento. O presente estudo procurou caracterizar o perfil cognitivo de pacientes com psicoses de início recente (n=56), até 3 anos após o primeiro contato com serviços de saúde mental, sendo 34 com esquizofrenia e 22 com psicoses afetivas. Tais grupos de pacientes tiveram seu desempenho cognitivo comparado com o de um grupo controles saudável (n=70), recrutados a partir das mesmas áreas geográficas de São Paulo, Brasil. Até o momento, a maioria dos estudos foi realizada em países em desenvolvimento. Metodologia: A investigação utilizou ampla bateria de testes neuropsicológicos composta por 12 testes agrupados em 8 domínios cognitivos destinados a avaliar respectivamente amplitude atencional, velocidade de processamento da informação, memória verbal, memória visual, memória de trabalho, fluência verbal, funções executivas e funcionamento intelectual. O nível de significância foi de p < 0.05. Resultados: O desempenho do grupo de pacientes com psicoses foi pior do que o dos controles em todas as tarefas cognitivas, com diferenças estatisticamente significativas nas tarefas de velocidade de processamento da informação, memória verbal, fluência verbal e funcionamento intelectual, sendo os déficits mais graves no domínio da memória verbal (p < 0.001). Os grupos esquizofrenia e psicoses afetivas não diferiram significativamente quando comparados entre si. A inclusão do grupo controle na comparação mostrou que os pacientes com esquizofrenia tiveram desempenho significativamente pior do que os controles, o que não ocorreu entre os controles e as psicoses afetivas. A investigação da influência das variáveis demográficas e clínicas mostrou que o desempenho cognitivo foi beneficiado pela escolaridade, na maioria das funções; a idade atual maior teve associação negativa com a memória visual e fluência verbal; gênero masculino teve correlação positiva com a memória de trabalho, tempo de latência para produção de resposta não-convencional, e negativa com a quantidade de erros frente à necessidade de controle de respostas impulsivas.O padrão de tratamento descontínuo beneficiou o desempenho em tarefas de memória verbal, e prejudicou o desempenho na tarefa de antecipação espacial. O abuso/dependência de substâncias não mostrou correlação com nenhuma tarefa, o que ocorreu na análise de regressão. O início do transtorno em idades mais precoces não mostrou prejudicar o desempenho dos pacientes na maioria das tarefas. O tempo de duração de psicose não tratada (duration of untreated psychosis, DUP) mostrou correlação negativa com o tempo de latência para respostas não-convencionais no grupo das psicoses, influenciando negativamente o desempenho nas tarefas de vocabulário, memória verbal imediata e tardia, e a quantidade de respostas impulsivas. No grupo da esquizofrenia, a maior DUP esteve associada a piores resultados nas tarefas de raciocínio não-verbal, memória verbal imediata e tardia, e quantidade de erros no teste de antecipação espacial. Os sintomas negativos influenciaram negativamente os resultados em várias provas, o que não ocorreu com os sintomas positivos. Conclusão: Pacientes com psicoses funcionais de início recente apresentaram prejuízos cognitivos evidentes em comparação aos controles saudáveis. Confirmou-se também a existência de funcionamento cognitivo semelhante entre amostras de países desenvolvidos e em desenvolvimento através de bateria cognitiva ampla. Os prejuízos cognitivos estenderam-se a várias funções, configurando tendência a perfil de déficits generalizados. Embora tenha havido tendência a maior gravidade de déficits no grupo da esquizofrenia, não encontramos diferenças significativas entre os subgrupos diagnósticos, confirmando a presença de déficits cognitivos nas psicoses de início recente, particularmente nas de natureza não-afetiva. / Background and Purpose: Functional psychoses are psychiatric disorders which have as their main characteristic a loss of the ability to properly judge the reality due to alterations of thought, perception, emotion, movement and behavior. The main psychotic disorder is schizophrenia, which usually as a chronic and / or deteriorating course in social and occupational relationships, generating enormous personal and financial costs for the patients and their caretakers all over the world. Previous studies have shown the presence of cognitive deficits in patients at the onset of psychoses, more severely in schizophrenia. There are evidences that those deficits are both related to disease processes and to treatment effects. The present work sought to characterize the neuropsychological profile of patients with recent onset psychoses (n=56), up to 3 years after their first contact with Mental Health Service Care 34 with schizophrenia and 22 with affective psychoses. These patient groups had their results compared to a healthy control group (n=70) recruited from the same geographic area of São Paulo City, Brazil. So far, most studies of neuropsychological functioning in patients with recent onset psychoses have been conducted in high-income countries. Method: The cognitive assessment was conducted using a neuropsychological battery comprising 12 tests, grouped into 8 cognitive domains aimed at assessing respectively intellectual functioning, attentional span, information processing speed, verbal memory, visual memory, working memory, verbal fluency and executive functioning. The significance level was set at p < 0.05. Results: The performance of the psychosis group was worse than that of controls in all cognitive tasks, with statistically significant differences detected in information processing speed, verbal memory, verbal fluency and intellectual functioning tasks, most seriously in the verbal memory domain (p < 0.001). When compared against each other, the schizophrenia and affective psychoses subgroups were not significantly different. The inclusion of the control group in the analysis showed that patients with schizophrenia had significantly worse performance than controls, while such difference was not noticed when controls and affective psychoses groups were compared against. The influence of demographic variables and clinic data showed that cognitive performance was significantly associated with level of schooling in most cognitive tasks; visual memory and verbal fluency were negatively affected by age (deficit increased with age); male gender showed a positive relationship to executive memory and lag time for non-conventional answers, and a negative relationship to mistakes in impulsive answer control needs. Treatment discontinuity was related to better performance in tasks such as verbal memory, but with worse performance in the anticipation space test. Substance abuse or dependence did not influence significantly the performance in any of the tasks individually, but this occurred in the regression analysis. Earlier age of psychosis onset was non significantly related to performance of patients in any of the tasks. The duration of untreated psychoses (DUP) showed negative correlation with the lag time for non-conventional answers in the psychoses group, influencing the performance in tasks as vocabulary, immediate and delayed verbal memory, and the amount of impulsive responses negatively. In schizophrenia group, DUP was associated to worse results in non - verbal reasoning, immediate and late verbal memory, and error quantity in anticipation space test. Several activities were negatively influenced by negative symptoms, what did not occurred with positive symptoms. Conclusion: Patients with recent onset psychosis clearly display cognitive deficits when compared to healthy controls. The existence of similar cognitive functioning between samples studied in developed and developing countries was confirmed through wide cognitive test sets. Cognitive impairment was detected in multiple tasks, showing a widespread trend of deficit profiles. Although there was a tendency towards high severity deficits in the schizophrenia group, we could not find major differences amongst diagnoses subgroups. Our results reinforce the view that there are generalized cognitive deficits in association with recent-onset psychoses, particularly of non- affective nature.

Childhood maltreatment is extremely common in patients diagnosed with psychotic disorders. Moreover, it has been linked with impaired functioning of the Hypothalamic-Pituitary-Adrenal axis. Furthermore, abnormality of the HPA has been found in psychotic patients. Presence of childhood maltreatment could then explain why the HPA axis is dysfunctional in these subjects. Our objective was to clarify the role of childhood trauma in the cortisol profiles of psychotic patients. Thirty-one patients underwent assessments of childhood maltreatment. Diurnal cortisol and cortisol after a controlled psychosocial stress were also collected. Our results show that childhood trauma is associated with lower cortisol levels during the morning and during 24 hours. In men diagnosed with psychosis, childhood trauma is also associated with a higher cortisol response during psychosocial stress. This suggests an alteration of the HPA axis in psychotic patients, resulting from early trauma. Moreover, our results suggest that looking at specific types of childhood abuse may also be important.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 5 uppsatser.

Over the past few decades, epidemiological evidence has accrued to establish variance in psychosis risk across both geographical locations and demographic characteristics such as the excess risk in migrants and their descendants. Yet, the causes of this variation in rates between places and ethnic groups are still unclear, and I aimed to address this in this thesis. I conducted a systematic review and meta-analyses to synthesise existing literature on psychosis incidence in the six countries included in the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study: England, The Netherlands, Spain, France, Italy and Brazil. I subsequently analysed data from two parts of the EU-GEI study: a 17-centre service-based incidence study of psychosis, and a case-control arm utilising community volunteers. In the latter, I aimed to explain excess risk in ethnic and religious minorities using a theoretical sociocultural distance model I developed using literature from the social sciences. Here, I proposed that culturally distant minorities were particularly at risk of social exclusion, and this outsider experience led to increased psychosocial disempowerment (a lack of control over one’s life), which increased psychosis risk. I also explored if this model could explain any excess risk in those with increased genetic African ancestry in England. Incidence varied substantially between the studies included in the systematic review, although methodological differences could not be excluded as an explanation. The EU-GEI incidence study confirmed substantial variation by place, and demonstrated a higher incidence in ethnic minorities and for young men, as well as in areas characterised by a low percentage of owner-occupied housing. The sociocultural distance model could explain most of the excess psychosis risk in ethnic minorities, although some excess risk remained, particularly in the Black ethnic group. Social and cultural distance appeared to be more important predictors than psychosocial disempowerment, suggesting that chronic social injustices rather than acute stress play an important role. This model did not explain excess risk in religious minorities: those following any religion retained an excess risk. It could explain the excess risk in those with increased genetic African ancestry, although this was a small, exploratory sample and this will need replicating in larger studies. This thesis demonstrated, for the first time, that excess risk in ethnic minorities could be explained by the sociocultural distance model. Overall, the findings from this thesis confirm substantial variation in psychosis risk by person and place, and suggest that the social reality of the environment plays a crucial role in explaining this.

Introduction: Cardiovascular disorders contribute significantly to mortality and morbidity amongst patient's psychotic disorders such as schizophrenia and bipolar mood disorders. In addition to conventional risk factors for cardiovascular disorders (smoking, alcohol use, inadequate physical activity, hypertension, diabetes, dyslipidaemia, obesity and metabolic syndrome, and non-modifiable factors such as sex, age and social-economic status) exposure to potentially traumatic events, psychological distress, comorbidity of other medical conditions, and use of antipsychotics may also increase cardiovascular risk in patients with psychosis. There is also evidence to suggest that intervention to mitigate such cardiovascular risk factors are suboptimal, hence contributing to poor outcomes. Despite growing interest in cardiovascular health, there remains a paucity of data on the prevalence of the various cardiovascular risk factors among patients with psychosis in low resource settings such as Sub-Saharan Africa. This is likely to differ from high resource contexts given social-cultural and economic differences as well as differences in the health systems. In order to design contextually relevant cardiovascular risk screening, treatment and prevention guidelines that can be integrated into routine care of the mentally ill patients in low- and middle-income countries (LMICs), further work in this setting is warranted. Objectives: The aim of this thesis was to establish the cardiovascular risk profile among patients treated for psychotic disorders at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Western Kenya. Specific objectives were as follows: 1. To conduct a literature review on the burden and etiological mechanisms of cardiovascular risk in patients with psychosis, with a focus on LMIC. 2. To compare the prevalence, as well as sociodemographic and clinical correlates, of conventional cardiovascular risk factors (smoking, alcohol intake, poor diet, and lack of exercise, diabetes mellitus, hypertension, obesity, dyslipidaemia and metabolic syndrome) in patients with psychosis versus matched controls. 3. To establish the prevalence and correlates of non-conventional risk factors; psychological distress, traumatic events (lifetime and childhood trauma) and comorbid medical disorders in patients with psychosis and controls, and to delineate how these risk factors contribute to the overall cardiovascular risk. 4. To describe current psychopharmacological treatments and explore potential associations with cardiovascular risk among patients with psychosis. 5. To explore the overall 10-year cardiovascular disease risk, as well as the social demographic and clinical correlates among patients and controls. 6 .To determine the proportion of untreated metabolic disorders (hypertension, diabetes mellitus, and dyslipidaemia) in patients with psychotic disorders and matched controls. Methods: This was a cross-sectional descriptive survey comparing 300 patients with psychosis and 300 controls at Moi Teaching and Referral Hospital, Western Kenya. A paper based researcher-administered questionnaire was used to collect data on demographic variables (age, sex, education level, and marital status), and risk factors (smoking, alcohol intake, diet, physical activity). We used the Composite International Diagnostic Interview (CIDI) to assess for presence of other chronic medical disorders. Data on childhood trauma were obtained using the Childhood Trauma Questionnaire (CTQ) while the Life Events Checklist (LEC) was used to obtain data on lifetime exposure to potentially traumatic events. Data on psychological distress among controls were obtained using the Kessler-10 questionnaire. Measurements of weight, height, abdominal circumference and blood pressure were taken from each of the participants. Blood was drawn for measurement of glucose level and lipid profile. Data analysis was undertaken using Stata version 15. T-tests were used to compare continuous variables while Pearson chi-squared tests was used for categorical variables. Regression modelling was undertaken to assess associations between sociodemographic and clinical predictor variables and the cardiovascular risk factors. Results: Data collection took place between July 2018 and March 2019. The mean age of patients was 33 years and of controls was 35 years. Compared to controls, patients were more likely to be unmarried (46% vs 33% p< 0.001), and were reduced among females (OR 0.41 p20). The estimated 10 year cardiovascular risk was significantly associated with female Sex (p=0.007), age (p <0.001), current tobacco smoking (p <0.001) and metabolic syndrome (P<0.001). Among the patients, 280 (94.3%) patients were on antipsychotics with the majority (86.5%) being treated with olanzapine. Of all the participants with diabetes 60% among patients and 22% among controls were not on treatment. Of the total number of participants with hypertension, 65% of patients and 47% controls were not on treatment. Conclusion: In the study setting of Eldoret, Western Kenya, patients with psychosis were found to have high levels of lifestyle cardiovascular risk factors such as smoking, inadequate intake of fruits and vegetables and inadequate physical activity. They were also found to have high rates of metabolic disorders such as hypertension, obesity, metabolic syndrome and dyslipidaemia. There was no evidence of increased cardiovascular risk among participants exposed to traumatic life events, with those experiencing psychological distress or those with other chronic medical disorders. The use of olanzapine was not significantly associated with increased cardiovascular risk in this setting. There was an identifiable gap in the treatment of cardiovascular risk factors in this setting. Given these findings, we recommend efforts to address these risk factors by development of protocols to ensure screening for these risk factors, adequate documentation and appropriate treatment.

No description available.

No description available.

Introduction: Through large neuroimaging consortia, researchers have identified a series of neuroanatomical alterations in mood and psychotics disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). However, the mechanism behind these alterations is not well understood. One of the existing hypotheses suggests that the observed brain changes are related to a process of accelerated brain ageing. Studies investigating this hypothesis use a measure called the brain age gap (i.e., the difference between machine learning model predictions of brain age and chronological age). Thus far, there is limited understanding on how mood and psychotic disorders affect model predictions, how can predictions be clinically useful, and what is the biological meaning behind the brain age gap. In this thesis, we investigated accelerated brain ageing in mood and psychotic disorders. We sought to estimate the effect of the brain age gap and propose new ways of modeling brain age. We also explored the clinical utility and meaning of the brain age gap. Results: We confirmed the presence of a brain age gap in MDD, BD, and SCZ through a systematic review and meta-analysis. SCZ presented the highest levels of brain age gap, followed by BD and MDD. We analyzed the clinical utility of brain age for antidepressant treatment response and concluded that the brain age gap is not a predictor of antidepressant treatment response in weeks 8 and 16. We proposed a new method for brain age prediction that is more interpretable than previous approaches while preserving good predictive performance. We have also used model explanation strategies and identified that the brain age gap is largely associated with total gray matter volume reduction and ventricle enlargement in SCZ. Conclusion: The results of this thesis suggest that the brain age gap is present across mood and psychotic disorders. The results have also helped to clarify the meaning behind the brain age gap, a largely used but still poorly understood measure in neuroimaging research. So far, there is no indication that the brain age gap can be a useful tool for treatment response prediction in MDD. / Thesis / Doctor of Philosophy (PhD)