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.

abstract: There is a robust association between psychosis and cannabis use, but the mechanisms underlying this relation are poorly understood. Because both psychosis and cannabis use have been linked to cardiovascular problems, it is possible that cannabis use exacerbates an underlying vascular vulnerability in individuals prone to psychosis. To investigate microvascular differences in individuals with psychotic symptoms and cannabis use, the current study tested associations between psychotic-like experiences, cannabis use, and retinal vessel diameter in 101 young adults (mean age=19.37 years [SD=1.93]). Retinal venular diameter did not differ between participants with (M=218.08, SD=15.09) and without psychotic-like experiences (M=216.61, SD=16.18) (F(1, 97)=0.01, p=.93) or between cannabis users (M=218.41, SD=14.31) and non-users (M=216.95, SD=16.26) (F(1, 97)=0.37, p=.54). Likewise, mean retinal arteriolar diameter did not differ between participants with (M=157.07, SD=10.96) and without psychotic-like experiences (M=154.88, SD=9.03) (F(1, 97)=0.00, p=.97). However, cannabis users had statistically significantly wider retinal arterioles (M=159.10, SD=9.94) than did non-users (M=154.29, SD=10.20) (F(1, 97)=5.99, p=.016), and this effect was robust to control for covariates. There was no evidence of an interaction between psychotic-like experiences and cannabis use in predicting retinal vessel diameter. These results indicate that cannabis use is associated with microvascular differences in young adulthood. Given current trends toward legalization of recreational cannabis use, future research should explore these differences and their potential consequences for cardiovascular health. / Dissertation/Thesis / Masters Thesis Psychology 2016

Introdução: A Depressão Psicótica (DP) afeta cerca de 15-20% dos pacientes com diagnóstico de depressão. Esta condição está ligada a maior cronicidade, maior incidência de tentativas de suicídio e maior frequência de internação hospitalar em relação à Depressão Não-Psicótica. No entanto, evidências recentes sugerem que a incidência de características psicóticas pode não estar relacionada à intensidade dos sintomas depressivos. O curso distinto de doença, associado a pior resposta ao tratamento e a pior prognóstico suscitam a discussão de que a depressão psicótica pode ser uma entidade clínica distinta da depressão, representando um ponto em um continuum que tem em um de seus extremos os transtornos psicóticos e no outro, os transtornos de humor. Objetivos: Avaliar se a presença de sintomas psicóticos em pacientes internados por episódio depressivo se correlaciona com a intensidade de sintomas depressivos. Avaliar se há diferenças clínicas e funcionais que podem se relacionar com os sintomas psicóticos dos pacientes da amostra. Observar a melhora de sintomatologia psiquiátrica ao longo da internação, e se há diferença na variação de sintomas, ao longo da internação, entre os pacientes psicóticos e não-psicóticos. Métodos: 288 pacientes internados por episódio depressivo em uma unidade psiquiátrica de um hospital geral universitário foram avaliados na admissão e na alta hospitalar. Foi realizada entrevista semi-estruturada com o MINI para avaliação diagnóstica. Nos dois momentos de avaliação foram aplicadas a Escala de Hamilton para Avaliação de Depressão (HAM-D), a Escala Breve de Avaliação Psiquiátrica (BPRS), a avaliação da Impressão Clínica Global (CGI) e a Escala Global de Avaliação do Funcionamento (GAF). Outros parâmetros clínicos e epidemiológicos também foram avaliados: idade de início de sintomas, quantidade de internações prévias, tentativas de suicídio prévias, tempo de duração da internação atual e realização de Eletroconvulsoterapia (ECT) durante a internação. Resultados: 131 pacientes (45,4%) apresentaram sintomas psicóticos. Após ajuste para controle de variáveis que tinham potencial de viés de confusão – história prévia de mania ou hipomania, história prévia de uso de substâncias, sexo, idade, e anos de estudo – os dois grupos tiveram resultados similares nos resultados da HAM-D, tanto na admissão quanto na alta. Em relação às outras medidas, no entanto, os pacientes com depressão psicótica apresentaram piores níveis de funcionamento (GAF), piores resultados na avaliação clínica (CGI) e escores mais elevados na BPRS, na admissão e na alta hospitalar. Conclusão: Os pacientes com depressão psicótica apresentaram história mais grave de sintomas psiquiátricos e maior prejuízo funcional. No entanto, as diferenças entre os pacientes psicóticos e não-psicóticos não tiveram relação com os sintomas depressivos dos pacientes. Tais achados vão ao encontro de evidências recentes que sugerem que a depressão psicótica pode ser um transtorno distinto da depressão maior. / Introduction: Psychotic Depression (DP) is a medical condition that affects a significant portion of depressive patients, 15-20%. This disorder is linked to greater cronicity, higher incidence of suicide attempts and a higher frequency of hospitalization, when compared to depressive episodes without psychotic features. Nevertheless, recent evidences suggest that the presence of psychotic symptoms may not correlate to depressive symptoms severity. The discrete clinical course, along with worse response to usual treatment and worse prognosis draw a hypothesis that Psychotic Depression might be a distinct disorder in relation to major depression. It reflects the intersection of psychotic and affective dimensions, and may be placed in a point of a continuum between psychotic and affective disorders. Objectives: To evaluate if the presence of psychotic symptoms in hospitalized depressive patients correlates to depressive symptoms intensity. To evaluate the existence of clinical and functioning differences among psychotic and non-psychotic depressive inpatients that could be related to the psychotic features. To estimate clinical improvement during hospitalization, and if there are dissimilarities in the variation of symptoms between psychotic and non-psychotic depressive individuals. Methods: 288 depressive inpatients of a psychiatric ward of a university tertiary hospital were assessed at admission and at discharge. We conducted MINI semi-structured interview to determine patient diagnosis. At both assessments we applied the Hamilton Depression Rating Scale (HAM-D), the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Other clinical and epidemiological parameters were also assessed: age at onset, number of previous hospitalizations, previous suicide attempts, length of stay and Electroconvulsive therapy (ECT) in current hospitalization. Results: 131 patients (45,4%) had psychotic features. After adjusting for potential confounding variables – previous presence of mania or hypomania, history of substance use, gender, age and years of study –, both psychotic and non-psychotic depressive patients presented similar HAM-D scores at admission and at discharge. However, psychotic depressive inpatients showed worse functioning levels (GAF), worse clinical status (CGI) and higher BPRS scores, both at admission and at discharge. Conclusion: Psychotic depressive inpatients presented more severe history of psychiatric symptoms and greater functioning disability. The differences between both groups of patients did not correlate to depressive symptoms. These findings are in conformity with recent evidences that suggest that psychotic depression might be a distinct disorder in relation to major depression.

Introdução: A Depressão Psicótica (DP) afeta cerca de 15-20% dos pacientes com diagnóstico de depressão. Esta condição está ligada a maior cronicidade, maior incidência de tentativas de suicídio e maior frequência de internação hospitalar em relação à Depressão Não-Psicótica. No entanto, evidências recentes sugerem que a incidência de características psicóticas pode não estar relacionada à intensidade dos sintomas depressivos. O curso distinto de doença, associado a pior resposta ao tratamento e a pior prognóstico suscitam a discussão de que a depressão psicótica pode ser uma entidade clínica distinta da depressão, representando um ponto em um continuum que tem em um de seus extremos os transtornos psicóticos e no outro, os transtornos de humor. Objetivos: Avaliar se a presença de sintomas psicóticos em pacientes internados por episódio depressivo se correlaciona com a intensidade de sintomas depressivos. Avaliar se há diferenças clínicas e funcionais que podem se relacionar com os sintomas psicóticos dos pacientes da amostra. Observar a melhora de sintomatologia psiquiátrica ao longo da internação, e se há diferença na variação de sintomas, ao longo da internação, entre os pacientes psicóticos e não-psicóticos. Métodos: 288 pacientes internados por episódio depressivo em uma unidade psiquiátrica de um hospital geral universitário foram avaliados na admissão e na alta hospitalar. Foi realizada entrevista semi-estruturada com o MINI para avaliação diagnóstica. Nos dois momentos de avaliação foram aplicadas a Escala de Hamilton para Avaliação de Depressão (HAM-D), a Escala Breve de Avaliação Psiquiátrica (BPRS), a avaliação da Impressão Clínica Global (CGI) e a Escala Global de Avaliação do Funcionamento (GAF). Outros parâmetros clínicos e epidemiológicos também foram avaliados: idade de início de sintomas, quantidade de internações prévias, tentativas de suicídio prévias, tempo de duração da internação atual e realização de Eletroconvulsoterapia (ECT) durante a internação. Resultados: 131 pacientes (45,4%) apresentaram sintomas psicóticos. Após ajuste para controle de variáveis que tinham potencial de viés de confusão – história prévia de mania ou hipomania, história prévia de uso de substâncias, sexo, idade, e anos de estudo – os dois grupos tiveram resultados similares nos resultados da HAM-D, tanto na admissão quanto na alta. Em relação às outras medidas, no entanto, os pacientes com depressão psicótica apresentaram piores níveis de funcionamento (GAF), piores resultados na avaliação clínica (CGI) e escores mais elevados na BPRS, na admissão e na alta hospitalar. Conclusão: Os pacientes com depressão psicótica apresentaram história mais grave de sintomas psiquiátricos e maior prejuízo funcional. No entanto, as diferenças entre os pacientes psicóticos e não-psicóticos não tiveram relação com os sintomas depressivos dos pacientes. Tais achados vão ao encontro de evidências recentes que sugerem que a depressão psicótica pode ser um transtorno distinto da depressão maior. / Introduction: Psychotic Depression (DP) is a medical condition that affects a significant portion of depressive patients, 15-20%. This disorder is linked to greater cronicity, higher incidence of suicide attempts and a higher frequency of hospitalization, when compared to depressive episodes without psychotic features. Nevertheless, recent evidences suggest that the presence of psychotic symptoms may not correlate to depressive symptoms severity. The discrete clinical course, along with worse response to usual treatment and worse prognosis draw a hypothesis that Psychotic Depression might be a distinct disorder in relation to major depression. It reflects the intersection of psychotic and affective dimensions, and may be placed in a point of a continuum between psychotic and affective disorders. Objectives: To evaluate if the presence of psychotic symptoms in hospitalized depressive patients correlates to depressive symptoms intensity. To evaluate the existence of clinical and functioning differences among psychotic and non-psychotic depressive inpatients that could be related to the psychotic features. To estimate clinical improvement during hospitalization, and if there are dissimilarities in the variation of symptoms between psychotic and non-psychotic depressive individuals. Methods: 288 depressive inpatients of a psychiatric ward of a university tertiary hospital were assessed at admission and at discharge. We conducted MINI semi-structured interview to determine patient diagnosis. At both assessments we applied the Hamilton Depression Rating Scale (HAM-D), the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Other clinical and epidemiological parameters were also assessed: age at onset, number of previous hospitalizations, previous suicide attempts, length of stay and Electroconvulsive therapy (ECT) in current hospitalization. Results: 131 patients (45,4%) had psychotic features. After adjusting for potential confounding variables – previous presence of mania or hypomania, history of substance use, gender, age and years of study –, both psychotic and non-psychotic depressive patients presented similar HAM-D scores at admission and at discharge. However, psychotic depressive inpatients showed worse functioning levels (GAF), worse clinical status (CGI) and higher BPRS scores, both at admission and at discharge. Conclusion: Psychotic depressive inpatients presented more severe history of psychiatric symptoms and greater functioning disability. The differences between both groups of patients did not correlate to depressive symptoms. These findings are in conformity with recent evidences that suggest that psychotic depression might be a distinct disorder in relation to major depression.

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.

Background: Autism spectrum disorders (ASD) are a group of complex developmental disabilities which can cause behavior, social, and communication deficits. Anti-psychotic medications are often prescribed when symptoms such as aggression, irritability, hyperactivity, tantrums, and self-injurious behavior occur. Objective: To determine if anti-psychotic medications improve the behavior, social, and communication symptoms associated with ASD in children and adolescents. Search Strategy: Electronic literature searches were performed to find relevant studies and utilized the (1) Cochrane Database of Systematic Reviews, (2) Hispanic American Periodicals Index, (3) Medline, (4) PAIS International, (5) ProQuest Dissertations and Theses, (6) PsycInfo, (7) PubMed, (8) Springer LINK, (9) Taylor and Francis Journals, and (10) Sage Premier. Selection Criteria: Randomized controlled trials (RCTs) or quasi-experimental design (QED) studies of any dose of an anti-psychotic medication compared to a placebo or other prescription drug, in participants with autism spectrum disorder. Data Collection and Analysis: All studies which met the full-text level criteria were reviewed by a third party to validate the decision of inclusion. Meta-analyses in this review implemented both random and fixed-effects models. Main Results: Ten RCTs were included. Six studies evaluated a drug versus a placebo and four studies investigated the effects of two separate anti-psychotic medications or the efficacy of an additive medication to a drug and placebo group. Author's Conclusions: Limited evidence suggests the effectiveness of anti-psychotic medications in treating the behavior, social, and associated with autism; however, further research is needed to determine the implications of long-term use.

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)

While many studies of risk factors for psychosis focus on positive symptoms, such as subthreshold levels of hallucinations and delusions, fewer studies have examined negative symptoms in the early course of the schizophrenia or other psychotic disorders. This relative lack of focus on the role of negative symptoms is problematic, given findings that negative symptoms, such as a loss of motivation and pleasure (MAP), are associated with a more persistent and impairing course of psychosis, and tend to appear earlier in the development of psychotic symptoms. Psychotic disorders, which afflict approximately 3-5% of the population, tend to emerge in late adolescence/early adulthood and are among the most debilitating and costly of mental disorders. The current project explored three areas of negative symptoms in young adults who demonstrated a range of psychotic-like experiences (PLEs). First, a review of the literature pertaining to negative symptoms across the span of psychosis was conducted. Second, we tested whether experiential negative symptoms – specifically MAP deficits – were associated with increases in PLEs, including those that are experienced as distressing (PLEDs). Third, we examined the potential influence of episodic memory performance factors on the relationship between MAP symptoms and PLEs/PLEDs. Collectively, this project highlights the importance of including negative symptoms (i.e., MAP deficits) and/or cognitive performance (i.e., associative/relational learning/memory) outcomes when evaluating people with PLEs/PLEDs to identify those who may be at greater risk for developing a psychotic disorder. / Psychology