▼ Background: Immigrants have diverse pre-immigration, peri-immigration, and post-immigration experiences. Despite being exposed to distinct mental health stressors, little is known about immigrant groups' service use for non-psychotic mental health disorders in the host country.Objective: Three studies assessed mental health service use by recent newcomers who settled in Ontario, Canada compared to use by age-and-sex matched long term residents (Canadian-born individuals or pre-1985 immigrants). Each study focused on one factor associated with one of the three stages of immigration: pre-immigration (region of origin), peri-immigration (admission class), and post-immigration (area material deprivation).Methods: Population-based administrative data sources were linked to measure primary care visits, psychiatrist visits, and hospital use (i.e., emergency department visits or hospital admissions) for non-psychotic disorders by recent immigrants (i.e., within five years of arrival)in Ontario during 1993-2012. Results: Immigrants' service use patterns for non-psychotic mental health disorders differed from long term residents, with immigrants generally using less mental health care. In the pre-immigration study on world region of origin, immigrants from all regions used less psychiatry and hospital services than long term residents, while immigrants' use of primary care relative to long term residents varied by region of origin.In the peri-immigration study on admission class, male refugees were more likely to use primary care than long term residents. No admission class of immigrants had greater use of psychiatry or hospital care than comparators. In the post-immigration study on material deprivation, immigrants were over-represented in deprived areas. While residence in more deprived areas was associated with greater use of primary and hospital mental health care, immigrants exhibited smaller increases in use than long term residents.Discussion: Given rising immigration levels globally and Ontario, reviews of existing practices and policies are necessary to better understand immigrants' lower use of mental health service use and different patterns of use than long term residents. Advisors/Committee Members: Glazier, Richard H, Health Policy, Management and Evaluation.

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Repetitive behaviours are a core feature and source of impairment in two neurodevelopmental disorders: obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD). However, few studies have systematically examined repetitive behaviours across these two disorders. As part of the Province of Ontario Neurodevelopmental Disorders network we compared repetitive behaviour subtypes in children and adolescents with OCD and ASD using several instruments. Findings revealed marked heterogeneity of repetitive behaviour subtypes in children and adolescents with OCD and ASD. Results suggest repetitive behaviour subtypes that are more common in OCD, ASD, and equally prevalent across disorders. Findings will help guide future pathophysiological studies by localizing dimensional traits of repetitive behaviours across disorders.

M.Sc.

Advisors/Committee Members: Arnold, Paul D, Medical Science.

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The objective of this study was to generate a deeper understanding of the influence of pre- and post-migration traumatic experiences on refugees’ psychological distress, including historical, political and social factors. This dissertation used a multi-method design to examine the impact of trauma on the psychological well-being of refugees. Further, the design included a qualitative component to provide a contextual framework for understanding refugee psychological distress that is not limited to an analysis of a disease model alone but by also making connections to important historical, social and political events. Post-Colonial, Refugee, Trauma and Feminist theories are used as analytic lenses to explain the social structures and events contributing to refugees’ pre- and post-migration traumatic events, and psychological distress. This was an international study that spanned two continents. Sampling included 50 Sri Lankan Tamil refugee participants who lived in Chennai, India and 50 Sri Lankan refugees in Toronto, Canada. Inclusion criteria included a residency period of the last 12 months in either of the sampling sites, and participants 18 years of age or older. Participants from Toronto were recruited through social service agencies and associations, and participants from Chennai were recruited from refugee camps, and the Organization for Elam Refugee Rehabilitation. Tamil versions of the Harvard Trauma Questionnaire, the Post-Migration Living Difficulties Questionnaire, and the Symptoms Check List – 90R were utilized to measure participants’ pre- and post-migration traumatic events and psychological distress. The Harvard Trauma Questionnaire contained qualitative open-ended questions to triangulate the quantitative data in identifying and exploring the impact of contextual influences. Results showed that post-migration traumatic event scores positively predicted psychological distress, and refugee claimants living in Canada had the highest scores on pre-migration and post-migration scores. The qualitative analysis revealed themes related to civil war and resettlement as significant issues. Implications of these findings support the development of a multi-level approach within social work practice which emphasizes contextual issues, focuses on individuals, and promotes social advocacy. Recommendations for future research point to conducting longitudinal studies to assess the cumulative effects of historical, social and political factors on refugees and identify resiliencies that mobilize their capacity to survive.

PhD

Advisors/Committee Members: Alaggia, Ramona, Social Work.

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To understand why some SCC experience psychological distress while others do not, researchers have turned their attention to potential protective factors that may influence the ability of SCC to cope with the cancer experience. Provision of protective/buffering factors specifically to less-resilient siblings (defined as those with higher initial depression and anxiety symptom scores) in the form of a structured program has not been previously attempted. The objective of this study was to explore outcomes of a specialized 8 week, intervention program for SCC. SCC and one parent completed standardized questionnaires exploring symptoms of depression and anxiety pre and post intervention. Results showed that the gender of the SCC, and the specific diagnosis of the child with cancer were factors significantly associated with the degree of reported symptoms of anxiety and depression respectively. Looking at significant interactions, we found that girls whose siblings had brain tumours improved less than other subgroups

MAST

Advisors/Committee Members: Barrera, Maru, Medical Science.

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The purpose of this study was to investigate the influence of childhood sexual, physical and emotional abuse and childhood emotional and physical neglect on eating disorder symptoms and general psychopathology. This study utilized a cross-sectional research design incorporating a combination of self-report measures and clinical interviews. Seventy participants were recruited from two eating disorder treatment centres. A series of univariate tests revealed no significant differences between individuals who reported a mild level of trauma and those who reported a severe level of trauma on all clinical measures. Logistic regression analyses revealed associations between impulsivity and childhood physical abuse and between psychiatric comorbidity and childhood physical neglect. Few associations were found and the observed effect sizes were generally small suggesting that the null findings were not due to inadequate power. It may be that the study sample differed from those used in previous investigations in which significant associations have been documented.

MAST

Advisors/Committee Members: Woodside, Blake, Medical Science.

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Background: Cognitive impairment and cannabis use are common among patients with schizophrenia. However, the moderating role of cannabis on cognition remains unclear. Aim: We sought to examine cognition and symptomatology as a function of cannabis use patterns in schizophrenia. Methodology: Cognition was assessed in male outpatients with current cannabis dependence (n=18), historical cannabis dependence (n=21) and patients with no lifetime use (n=8). In addition, we explored the relationship between cumulative cannabis exposure and cognition among lifetime users. Results: Lifetime cannabis users demonstrated better processing speed than patients with no lifetime use. Notably, patients with current dependence exhibited robust relationships between cumulative cannabis exposure and cognition; associations were absent in former users. Conclusions: Cannabis status has minimal effects on cognition in schizophrenia. However, cumulative cannabis exposure significantly impairs cognition in current, but not former users, suggesting that the state dependent negative effects of cannabis may be reversed with sustained abstinence.

MAST

Advisors/Committee Members: George, Tony Peter, Medical Science.

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The present study evaluated the cortisol stress response and its relationship to several behavioural measures in SAD participants. It is hypothesized that SAD participants will show an exaggerated cortisol response to the Trier Social Stress Test (TSST) and differing positive and negative affects compared to controls, as well as correlations between the two measures. SAD (n=12) and controls (n=12) underwent the TSST. Serial plasma cortisol samples were taken and self-report measures were completed. The plasma cortisol levels were numerically higher in SAD at all time points compared to controls but the difference was not statistically significant. Cortisol response correlated inversely with childhood emotional abuse (p=0.01) and directly with positive affect (p=0.02) in SAD participants. Furthermore, SAD participants reported greater negative affect (prior to and after TSST) and more frequent emotional abuse than controls. SAD is associated with changes in HPA axis activity and affective states that differ from controls.

MAST

Advisors/Committee Members: Ravindran, Arun, Medical Science.

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Objectives: 1) To assess the prevalence of occupational burnout and depression among pediatric dentists in the United States, and 2) To explore for differences in the prevalence of burnout/depression based upon gender, age, marital status, clinical practice type, geographical location, number of years in clinical practice, and number of hours worked per week. Methods: A self-administered online anonymous survey using Survey Monkey速 was sent to all active members of the American Academy of Pediatric Dentistry residing in the United States. The survey included: 1) demographic information; 2) the Maslach Burnout Inventory (MBI); and 3) the Patient Health Questionnaire 8 (PHQ-8). Results: A total of 4,735 pediatric dentists received the survey questionnaires and resulted in 540 usable responses (response rate = 11.40%). The prevalence of occupational burnout and depression were 9.1 and 7.2 percent respectively. Conclusions: A small but notable number of U.S. pediatric dentists had occupational burnout and depression.

M.Sc.

Advisors/Committee Members: Nainar, Hashim, Dentistry.

▼ Reductions in drive and goal-directed behaviour have long been described as key features of schizophrenia. This thesis contains several investigations into the motivational deficits present in people with schizophrenia. Despite not being required for the diagnosis, motivational deficits were found to be a highly prevalent feature of the disease, even among younger patients who were relatively early in their course of illness. Using cross-sectional and longitudinal follow-up study designs, and across two studies with different participants, motivational deficits were found to hold strong predictive value for the determination of functional outcomes. After establishing the importance of motivational deficits in terms of outcomes, underlying behavioural mechanisms were explored using experimental paradigms. Several candidate reward processes were examined concurrently, including valuation of outcomes, estimation of the costs associated with obtaining outcomes, and learning the association between actions and outcomes. Our results provide support for the proposal that individuals with schizophrenia have impairments in their ability to compute effort demands, and that these impairments translate into real-world reductions in goal-directed behaviour. Beyond mechanisms, this thesis also examined the inter-relationship between motivational deficits and another key domain of psychopathology in schizophrenia, namely, cognition. Although these two domains are thought of as distinct, two studies included in this thesis provide empirical evidence of an association, which is interpreted within a theoretical framework whereby poor motivation translates into reduced effort put forth during cognitive testing, which ultimately results in poorer submaximal test performance. Finally, the last study included in this thesis addresses the issue of treatment-induced symptoms. This study failed to find support for the contention that treatment with antipsychotic medications necessarily worsens the severity of motivational deficits in schizophrenia. Taken together, these investigations highlight the importance of motivational deficits in schizophrenia, and lay the foundation for a mechanistic understanding of these impairments. Advisors/Committee Members: Remington, Gary, Medical Science.

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This study investigated the hypothesis that severity of depressive symptoms following acute ischemic stroke is associated with degree of tissue infarction and severity of white matter changes (WMCs). It employed a novel quantitative region-based approach considering both infarction and WMCs. Of 54 ischemic stroke patients recruited, 50 (72.3 ± 12.8 years, 52.0% male) had useable CT scans. The typical patient was recruited within 3 weeks of their stroke (19.7 ± 31.0 days), exhibited minor cognitive impairment (MMSE score 25.8 ± 4.6), and had mild to moderate stroke severity (NIHSS score 6.5 ± 5.4). 28.0% of patients screened positive for clinical depression with a CES-D score ≥16. While neither degree of infarction nor severity of WMCs (ARWMC score) in the 12 brain regions correlated with depressive symptoms (CES-D score), stroke severity was a significant predictor of depressive symptoms. This stressor, related to physical disability, was a predominant predictor over lesion characteristics.

MAST

Advisors/Committee Members: t, Kris, Pharmacology.

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Objectives: High frequency left-sided (HFL) and low frequency right-sided (LFR) unilateral repetitive transcranial magnetic stimulation (rTMS) are efficacious in treatment-resistant major depression (TRD). Similar benefit has been suggested for sequential bilateral rTMS (LFR then HFL). Therefore, this study evaluated the efficacy of HFL and sequential bilateral rTMS compared to sham in TRD. Methods: Seventy-four subjects between the ages of 18 and 85 with TRD and a 17-item Hamilton Depression Rating Scale (HDRS) greater than 21 were randomized to receive unilateral, bilateral, or sham rTMS. Remission rates were compared among the three groups. Results: Remission rates differed significantly among the three groups. The remission rate was significantly higher in the bilateral group (34.6%) than the unilateral (4.5%) and sham (5.0%) groups. The remission rate in the unilateral group did not differ from sham group. Conclusion: These findings warrant larger controlled studies that compare the efficacy of sequential bilateral rTMS and HFL rTMS in TRD.

MAST

Advisors/Committee Members: Daskalakis, Zafiris Jeff, Medical Science.

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The purpose of this study was to examine the retraining and career development experiences of new and professional immigrants in Canada. The study intended to provide an in- depth perspective into the influence of immigrants’ optimism and self-efficacy on their retraining and career development experiences. Using a qualitative methodology, in-depth interviews were conducted and a grounded theory approach was employed to analyze the data. Central themes within participant narratives emerged and key results were introduced. Participants’ experiences included a myriad of barriers and challenges, yet many viewed this experience as a positive opportunity for growth and development. The results explored differences between optimists’ and pessimists’ retraining and career development experiences, as well as the role of self-efficacy within immigrants’ career development. Results have implications for career and vocational psychology literature, practice, and career counselling, and include suggestions for future researchers.

MAST

Advisors/Committee Members: Chen, Charles, Adult Education and Counselling Psychology.

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Patient-related barriers may reduce the effectiveness of screening for depression. This study aimed to explore perceived barriers to participation in a Screening Program for Depression by hemodialysis patients. In a cross-sectional study of hemodialysis patients, the Perceived Barriers to Psychological Treatment questionnaire was used to measure barriers to the Screening Program. Of 160 participants, 73.1% perceived at least one barrier (95% CI, 66.2% to 80.0%). The most common barriers were concerns about the side effects of antidepressant medications (40%), concerns about having more medications (32%), feeling that the problem is not severe enough (23%), and perceiving no risk of depression (23%). A high depression score was an independent predictor of barriers related to perceiving no benefit of the Screening Program and psychological, social, and practical barriers. We believe that patient-related barriers need to be addressed before implementing any case identification and treatment program for depression.

MAST

Advisors/Committee Members: Logan, Alexander, Health Policy, Management and Evaluation.

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The present study examined the associations among perfectionism, emotion dysregulation, and GAD. Eighty participants completed self-report questionnaires assessing perfectionistic tendencies, difficulties in emotion regulation, and symptoms of GAD. The purpose of this study was to examine emotion dysregulation as a potential mediator in the relationship between perfectionism and GAD. Results indicated that general emotion dysregulation statistically mediated the relationship between the socially prescribed dimension of perfectionism and GAD. In addition, specific difficulties in emotion regulation, including deficits in acceptance of emotions, emotional clarity, impulse control, and access to effective regulation strategies, fully mediated the association between socially prescribed perfectionism and GAD symptoms. Implications for treatment and future research directions are discussed.

M.A.

Advisors/Committee Members: Watson, Jeanne, Applied Psychology and Human Development.

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Altered glutamatergic neurotransmission is implicated in schizophrenia etiology and response to the atypical antipsychotic clozapine. Response to clozapine is highly variable and partly depends on genetic factors as indicated by twin studies. The association of 17 glutamate system gene variants and clinical response to clozapine was investigated in a sample of European schizophrenia/schizoaffective patients deemed resistant/intolerant to previous pharmacotherapy. Categorical and continuous response measures were assessed following six months of clozapine treatment using change in Brief Psychiatric Rating Scale Scores, and were analyzed using Pearsonâ s chi-squared test or analysis of covariance, respectively. No significant associations were observed for all analyses after correction for multiple testing. Prior to correction, several nominally significant associations were observed, the most notable being between the SLC6A9 rs16831558 variant and change in positive symptoms (puncorrected=0.008, pcorrected=0.08). This finding warrants further investigation in larger well-characterized samples to clarify the role of SLC6A9 in clinical response to clozapine.

M.Sc.

Advisors/Committee Members: Kennedy, James L, Medical Science.

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The current literature surrounding their mental health outcomes is limited. This study addresses limitations in the field by using healthcare administrative databases to compare the rates of mental health care utilization and the risk for a severe mental health episode between pediatric cancer survivors and matched population controls. Additionally, this study assesses the impact of demographic, disease, and treatment level predictors on mental health outcomes. Overall, pediatric cancer survivors were more likely to utilize mental health care (Adjusted Rate Ratio 1.31, 95% CI 1.16-1.48), but were not at greater risk of severe mental health episodes (Hazard Ratio 1.11 95% CI, 0.99-1.25). Pediatric cancer survivors were identified to be at increased risk of mood/affective disorders and psychotic disorders. In general, predictors of mental health outcomes in survivors were similar to those in the general population. This study provides novel information to a limited field, and a strong platform for future studies.

M.Sc.

Advisors/Committee Members: Nathan, Paul, Medical Science.

▼ The social, economic and health burdens of mental and behavioural disorders are large, and although treatment rates for such disorders are low, the use of emergency departments for mental and behavioural disorders is high. Accordingly, this thesis compares the use of disability, functioning, non-specific psychological distress and diagnosis to characterize mental and behavioural disorders. Furthermore, this thesis examines if predisposing and levels of mental illness factors are correlated to baseline and subsequent emergency department visits. The general population surveys of the 2011, 2012 and 2013 Centre for Addiction and Mental Health (CAMH) Monitors were used as a general population sample of Ontario adults. Data from patients were obtained by time-based sampling from August 2011 to February 2012 in the emergency department of CAMH (a psychiatric hospital that provides services to adults); the CAMH emergency department database was used to track subsequent emergency department visits. Disability and functioning were measured using the World Health Organization Disability Assessment Schedule, and non-specific psychological distress was measured using the General Health Questionnaire. Data from the CAMH Monitors indicated that although disability, functioning and non-specific psychological distress are correlated (except for people with somatic illnesses), all such measures are needed to accurately describe mental health. Among patients in the psychiatric emergency department, differences in disability and functioning were not significant across diagnoses; however, a substantial heterogeneity in disability and functioning was observed within diagnoses. Furthermore, using data from patients in the psychiatric emergency department, we observed that the number of previous visits, the WHODAS scores, and employment status were predictors of psychiatric emergency department recidivism. Based on the results of this study, it is clear that measures of disability, functioning and non-specific psychological distress may be needed to adequately describe the mental health of the general population. Furthermore, in psychiatric as well as in general hospital emergency departments, data on disability and functioning and on the number of previous visits if collected in addition to diagnosis data for patients with mental and behavioural disorders could lead to more effective triaging of these patients, alignment with the appropriate intensity of resources, and prediction of recidivism. Advisors/Committee Members: Rehm, J端rgen T, Medical Science.

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Siblings of children with cancer encounter stressors and challenges that can lead to severe distress and a host of psychological difficulties. Factors including age, gender, and disease characteristics of the child with cancer are reported to influence sibling adjustment. The majority of research, however, is dated, inconsistent, and marred by methodological problems. Guided by the disability-stress-coping model, the study examined the: (a) frequency of sibling and parent reported symptoms of anxiety and depression, internalizing and externalizing behavior problems, and somatic problems, (b) influence of sibling, family, and disease factors on sibling adjustment, (c) moderating effects of age on the relationship between sibling factors and sibling adjustment, and (d) mediating effect of primary cognitive appraisal on the relationship between self-esteem and sibling adjustment. One hundred and eight siblings (7-17 years; 51 males; 57 females) participated. Siblings completed the State-Trait Anxiety Inventory for Children and the Children’s Depression Inventory to provide measures of sibling reported symptoms of anxiety and depression. Parents completed the Child Behavior Checklist to provide measures of parent reported internalizing behavior problems, externalizing behavior problems, and somatic problems. The communication and intrapersonal thoughts and feelings subscales of the Sibling Perception Questionnaire, completed by siblings, were used to assess perceived social support and primary cognitive appraisal. Self-esteem was assessed with the global self-worth subscale of the Self Perception Profile for Children/Adolescents, completed by siblings. Hierarchical regression analyses were conducted to assess the direct and indirect effects of sibling, family, and disease factors on psychological outcomes. Siblings and parents reported higher incidents of clinically significant symptoms of anxiety, internalizing behavior problems, and somatic problems than expected in a normative population. Sibling age and gender, diagnosis of the child with cancer, social support, self-esteem, and primary cognitive appraisal were significantly associated with sibling and parent reported psychological adjustment measures. Age moderated the relationship between gender, social support, and primary cognitive appraisal and several adjustment outcomes. Lastly, primary cognitive appraisal partially mediated the relationship between self-esteem and sibling reported anxiety and depression symptoms. These findings highlight the need for sibling psychosocial interventions and provide direction for the development and implementation of such groups.

PhD

Advisors/Committee Members: Barrera, Maru, Human Development and Applied Psychology.

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The past two decades have witnessed an accelerated effort to understand the nature of schizophrenia and related psychotic disorders, but no causative gene(s) has been discovered yet. Family, twin, and adoption studies indicate that genetic factors are clearly implicated in the etiology of these disorders (Cardno and Gottesman, 2000; Cardno et al., 2002; McGuffin et al., 2003; Weinberger, 2005). Several aspects of 22q11 Deletion Syndrome (22qDS) - the most common chromosomal microdeletion found in humans - create a unique opportunity for susceptibility gene identification. For instance, the reported risk of psychotic disorders in 22qDS is 25-fold higher than in the general population (Murphy et al., 1999) and genome-wide linkage studies in families with schizophrenia without 22qDS indicate that the 22q11.2 region is a strong susceptibility locus for psychosis (Badner and Gershon, 2002; Lewis et al., 2003). This thesis aims to identify genetic factors associated with the development of psychosis in 22qDS by i) investigating the relationship between the length of the 22q11.2 deletions and the presence of a psychotic disorder in patients with 22qDS; ii) studying diagnostic molecular methods that improve detection of 22q11.2 deletions and duplications; and iii) exploring the relationship between 22qDS-psychotic phenotype and gene expression patterns. The central hypothesis was that psychosis in 22qDS would not be associated with haploinsufficiency (having one copy of the gene), but rather, it would be associated with distinct 22q11.2 gene expression profiles. Chapter 2 showed that 22q11.2 deletion size did not appear to be associated with the development of psychosis in adults with 22qDS. In Chapter 3, a molecular method that detects and size 22q11.2 deletions and duplications of various sizes was shown to be superior to the traditional molecular diagnostic technique used for molecular diagnostic of 22qDS. Finally, in Chapter 4, decreased gene expression of three genes located in the 22q11.2 region (SNAP29, COMT and BID) was significantly associated with psychosis in adults with 22qDS. Focusing on genes located in the 22q11.2 region has helped revealing genetic alterations associated with the frequent development of psychosis in 22qDS. Future studies focusing on investigating the heterogeneity of the psychotic presentation in 22qDS and further elucidating potential genetic mechanisms likely to explain the gene expression changes in the 22q11.2 region demonstrated here will help advance the scientific understanding of the etiology of psychosis.

PhD

Advisors/Committee Members: Siminovitch, Katherine A., Medical Science.

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Individuals with schizophrenia are at high risk for obesity. Contemporary treatment approaches have concentrated on improving diet and physical activity behaviour. Guided by the Medical Research Council Framework, this thesis aimed to identify modifiable environmental factors that may influence the dietary and physical activity behaviours of clients at a psychiatric facility and examine the efficacy of intrapersonal and environmental components of a broad ecological intervention. Study one explored what environmental factors at the facility influence diet and physical activity. Participants identified that obesogenic elements involved aspects of the social and built environments and that both intrapersonal interventions and environmental changes are needed to improve physical activity and dietary behaviour. Based on the findings of the first study, study two examined the feasibility of exercise counseling amongst individuals with schizophrenia and its effect on increasing moderate and vigorous levels of physical activity (MVPA). Findings showed that exercise counseling is feasible. Accelerometer results showed that levels of MVPA decreased throughout the study, but levels of mediating psychological variables of physical activity increased. Study three examined the use of point-of-choice prompts to increase stair use at the hospital. Overall, no significant changes in stair use between the study phases were found, but male staff members increased their stair use throughout the study. Using multiple research methods, this thesis has made several contributions to the understanding of physical activity and dietary behaviours in individuals with schizophrenia. Novel solutions are needed to move beyond lifestyle interventions and address multiple individual and environmental factors that cause weight gain in this population.

PhD

Advisors/Committee Members: Faulkner, Guy, Exercise Sciences.

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Despite significant advances in the field, functional impairment continues to be a characteristic feature of schizophrenia. Negative symptoms, and in particular motivational deficits, along with cognitive dysfunction have consistently been linked with functional impairments in schizophrenia. However, most investigations of functional outcomes have focused on discrete symptoms, or alternatively on broad symptom domains. Further, recent findings have suggested that a lack of motivation may contribute to the cognitive impairment seen in schizophrenia. This series of investigations sought to: 1) advance our understanding of the determinants of cross- sectional and longitudinal community functioning in schizophrenia by examining the concurrent contribution of negative symptoms, cognition, and other important symptoms to longitudinal functioning in schizophrenia over one year; and 2) clarify the relationships between motivation, effort exerted during cognitive testing, and cognitive performance in schizophrenia. We hypothesized that: 1) motivational deficits would serve as the most important and stable determinant of community functioning, with cognition offering additional predictive value; and 2) motivational deficits would exhibit a differential relationship across various cognitive domains, with those exhibiting reduced effort during testing evincing more severe motivational deficits. Seventy stable adult outpatients with schizophrenia or schizoaffective disorder underwent clinical, cognitive, and functional evaluations at baseline, 6 months, and 12 months. Using stepwise and hierarchical regression analyses, motivational deficits emerged as the most predictive and reliable determinant of cross-sectional and longitudinal community functioning, accounting for up to 58% of the variance in functioning. Other symptom domains exhibited substantially less predictive value for functioning. Motivational deficits also exhibited a differential relationship across cognitive domains, with a particular relationship with verbal fluency. Further, effort during cognitive testing appeared to be related to both cognitive dysfunction and motivation, suggesting that the use of performance validity tests in schizophrenia may not be an appropriate index of mental effort. Overall, these findings highlight the central role motivational deficits play in determining outcomes in schizophrenia, as well as their impact on cognitive dysfunction in this illness. Importantly, in spite of advances in treatment, this work points to the essential need for interventions to address these motivational deficits if we hope to improve outcomes in schizophrenia.

PhD

Advisors/Committee Members: Remington, Gary, Medical Science.

▼ Providing accessible education for students with mental health problems is an important aspect of social inclusion, as it increases educational attainment, subsequent employment opportunity and community participation. In universities, accommodations are provided where necessary with the intent of ensuring equal opportunity for all students. Despite the availability of accommodations, students with mental health problems continue to experience difficulty achieving academic success, suggesting a disjuncture between accommodations and their expected favourable outcomes within the social organization of the university. This Institutional Ethnography explores the social organization of university accessibility for students with mental health problems. Sixteen students with mental health problems and eight staff members of a large university in an urban setting participated in interviews focusing on the processes of seeking and implementing accommodations. I explored institutional texts for their ability to coordinate the actions of people in this setting, as the social organization of this university is informed by numerous texts that guide participants' work. Data analysis focused on asking questions of the data and mapping work processes, in order to develop an understanding of the social organization of accessibility and accommodation for these students. In the findings, I map and explicate what I have termed an "institutional accessibility mechanism", the set of work and texts that guide the university's social relations around accommodation and accessibility. These social relations involved staff and student work processes that maintained the mechanism and preserved institutional relations. Through the Institutional Accessibility Mechanism, the university appeared to place a focus on accommodation over accessibility and created work for individual students seeking access. This Mechanism also operated under assumptions of mental wellness and presented challenges for students with mental health problems. These findings have important implications for the development of higher education policies, which can enable students with mental health problems to have better chances of success in their academic endeavours. Promoting the inclusion of students with mental health problems in university can improve their educational and employment opportunities and further the prosperity of society as a whole. Advisors/Committee Members: Bonnie, Kirsh, Rehabilitation Science.

▼ Workplace mental health is becoming of increasing importance, in part due to the rising social and economic costs of mental health issues in the workplace. Little is known about how the experience of workers with mental health issues is actively produced through their participation in workplace procedures and associated supports. The purpose of this research is to better understand how employees actively engage in institutional practices and associated social relations that ultimately coordinate and produce their workplace experience. Using institutional ethnography, I take up the standpoint of the employee living with mental health issues to explore the coordinating relations associated with workplace mental health. This approach sheds light on how employees' experiences are socially produced and coordinated across and between institutional processes and practices. Data collection included over 140 hours of ethnographic observations, the analysis of associated texts and documents, and interviews that were conducted with 17 informants. This research details some of the challenges experienced by one novice health science researcher while conducting ethnographic research, and provides techniques for addressing personal and professional boundaries, negotiating ethical dilemmas, and reconciling the emotional experience of transitioning back and forth between being an `outsider' and `insider'. In addition to these insights, the findings explicate the social relations and institutional processes that coordinate sick time utilization for workers experiencing mental health issues. We revealed that employee's work of managing workplace absence management programs while negotiating episodes of mental ill health was perceived as overwhelming, unfair, and even punitive. Employees would require formal and informal respite from work, and would often utilized vacation time when unwell in order to avoid institutional processes all together. The biomedical focus of the absence management program created uncertainty about what constitutes a bona fide illness, and caused managers to come to know their work activities as distinctively separate from the work of healthcare practitioners. This research contributes to the literature by highlighting how tensions are created through textually coordinated work activities within and between the corporate and healthcare sector. These insights are important in establishing where and how to enact change from the standpoint of the worker. Advisors/Committee Members: Kirsh, Bonnie, Rehabilitation Science.

▼ Background: Bipolar disorder (BD) is associated with increased levels of inflammatory cytokines, which may contribute to cognitive dysfunction. Anti-inflammatory intervention with minocycline is hypothesized to exert antidepressant and pro-cognitive effects in BD. The aims of the investigations were: 1) to identify inflammatory cytokine abnormalities in BD; 2) to identify inflammatory cytokines associated with cognitive dysfunction in BD; 3) to evaluate the efficacy of adjunctive minocycline for symptoms of bipolar depression and cognitive dysfunction. Method: The first two study aims were evaluated with cross-sectional exploratory methods, comparing 29 depressed (HAMD-17 ≥ 20) and 46 euthymic (4 week verification) adults with DSM-IV-TR-defined BD as well as of 31 healthy controls (HCs). Plasma cytokine levels were measured with a 30 V-PLEX immunoassay. Evaluated cognitive domains were verbal memory, executive function and psychomotor speed. The efficacy of adjunctive minocycline (100 mg b.i.d.) was evaluated in an overlapping sample of depressed individuals (intent-to-treat: n=27) using an 8-week, open-label study. The primary efficacy measure was the MADRS, while, cognitive composites and plasma cytokines were secondary outcome measures. Results: Results from multinomial logistic regression analyses indicate that IL-6 levels were increased in depressed and euthymic individuals with BD when compared to HCs, while, levels of CCL3, IL-15, and IL-17A were reduced below levels of HCs in euthymic individuals (Pseudo R2=.648, p Advisors/Committee Members: Kennedy, Sidney K, McIntyre, Roger S, Medical Science.

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Although many advances in the treatment of schizophrenia have been made over the past decade, little is known about the process of recovery from a first episode of schizophrenia (FES). To date, the study of recovery in the field of mental health has focused on long-term mental illness. This in depth qualitative study drew upon Charmaz’s (1990) constructivist grounded theory methodology to address the following questions: How do individuals who have experienced a FES describe their process of recovery? How does an identified individual (e.g. friend, family member, teacher, or clinician) describe their role during the participant’s process of recovery, and their perception of the recovery process? Ten primary participants (who self-identified as recovering from a FES) had two interviews; in addition, there was a one-time interview with a secondary participant, for a total of 30 interviews. Data collection sources included participant semi-structured interviews, participant selected personal objects that symbolized their recovery, and clinical records. The results provide a substantive theory of the process of recovery from a FES. The emergent process of recovery model for these participants is comprised of the following phases: ‘Lives prior to the illness’, ‘Lives interrupted: Encountering the illness’, ‘Engaging in services and supports’, ‘Re-engaging in life’, ‘Envisioning the future’; and the core category, ‘Re-shaping an enduring sense of self,’ that occurred through all phases. A prominent distinctive feature of this model is that participants’ enduring sense of self were reshaped versus reconstructed throughout their recovery. The emergent model of recovery from a FES is unique, and as such, provides implications for clinical care, future research, and policy development specifically for these young people and their families.

PhD

Advisors/Committee Members: Goering, Paula N., McCay, Elizabeth, Medical Science.

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BACKGROUND: Teratology Information Services (TIS) educate the public and health professionals via telephone regarding the safety of drugs and other exposures during pregnancy and lactation. Currently TIS consultations are free, but funding is eroding. A cost-benefit analysis may inform resource allocation. It was hypothesized that an individual TIS consultation regarding anti-depressant use during pregnancy provides a positive net benefit compared to a family doctor (FD) consultation. METHODS: A survey of international TIS was conducted to gauge TIS costs. A discrete choice experiment (DCE) was designed to assess preferences and willingness-to-pay (WTP, an estimate of benefit) for teratology counseling. DCE respondents (local community volunteers) chose between potential counseling services following an anti-depressant exposure during pregnancy. Services were described by five service attributes and one cost attribute, which were generated in focus groups. Preferences and WTP were estimated using logit regression. Incremental benefits and costs of counseling by TIS and FD were compared in a probabilistic sensitivity analysis to obtain the incremental net benefit from both a societal (productivity costs included) and health system perspective. The FD consultation was costed through OHIP billing codes. The TIS consultation was micro-costed. RESULTS: Eighteen TIS in North America and 16 international TIS completed the survey. Most TIS are small (median two employees, median budget US69,000). The DCE had 175 respondents. The most important attribute of counseling was receiving very helpful information; information delivery methods were less important. WTP for the TIS scenario was CDN124 (SD 12); WTP for the FD scenario was CDN79 (SD 8). Service costs were similar for TIS and FD (approximately 32/consultation); FD had higher productivity costs. Incremental TIS benefits were likely to outweigh costs under both the societal and health system perspectives (probability 99% and 97% respectively). CONCLUSIONS: An economic evaluation of a program that delivers pregnancy health information via telephone required a novel approach. While there are some methodological challenges to valuing benefits through willingness-to-pay, it may be appropriate for valuing counseling. TIS should emphasize their ability to provide high quality information. The benefits of an individual TIS consultation on anti-depressant use during pregnancy are likely greater than the costs.

PhD

Advisors/Committee Members: Ungar, Wendy Joan, Medical Science.

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Interpatient variability in clinical response to antipsychotics (AP) is observed in the treatment of schizophrenia (SCZ) with evidence to support a genetic basis for this phenomenon. Dysfunction in the dopaminergic (DA) system as well as the glutamatergic (GLU) system have both been implicated in the formation of SCZ symptoms. Therefore, we explored the role of DA and GLU receptor variation on clinical response to CLZ, an AP of last resort. We focused on DA receptor genes DRD3, DRD4, and DRD5 having already previously published on DRD1 and DRD2 in this sample. N-methyl-D-aspartate receptor (NMDAR) subunit gene variants and epistatic effects between and among these variants and DA receptor gene variants were also studied. For DRD3, we extended a statistically significant meta-analysis on single nucleotide polymorphism (SNP) rs6280 (Ser9Gly) previously performed by Jonsson et al. (2003). We observed a consistent trend for the serine allele and poor CLZ response (six of seven studies with the same direction of effect). Eight other tagged DRD3 SNPs were also tested with two identified for future replication. For DRD4, associations were observed between the 4-repeat allele of the exon III variable number tandem repeat (VNTR) polymorphism and better CLZ response in Caucasians with a non-significant but same direction of effect in African-Americans; the 142/140-base pair (bp) genotype of the intron 1 guanine mononucleotide repeat ((G)n) polymorphism with poor CLZ response in the whole sample; and the 1-copy allele of the 5’-flanking region 120-bp tandem repeat polymorphism in African-Americans. Three other tagged SNPs across DRD4 and five across DRD5 were negative. Our investigation of GLU receptor gene variants focused on NMDAR subunit genes GRIN1, GRIN2A, and GRIN2B with negative findings. Examining gene-gene epistatic effects among and between NMDAR subunit and DA receptor gene polymorphisms identified several interactions with the strongest result being between the DRD1 rs686 G carrier/DRD3 Ser9Gly G non-carrier group with good response. Overall, our results suggest possible minor roles for DA receptor gene variants on CLZ response. Integrating this data with exciting new advances in technologies and bioinformatics will surely bring us closer to personalized medicine in psychiatry.

PhD

Advisors/Committee Members: Kennedy, James L., Medical Science.

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This thesis uses observational study design methods to explore the relationship between depression and various outcomes following acute myocardial infarction (AMI). There are three main studies. First, the relationship between depression and mortality following AMI was measured. The main finding was that the factor determining the increased mortality rate in depressed patients is reduced cardiac functional status. The main implication was that efforts to address increased mortality in depressed patients with cardiovascular illnesses should focus on processes that impact cardiac functional status. Second, the impact of depression on service consumption following AMI was examined. Depressive symptoms were associated with a 24% (Adjusted RR:1.24; 95% CI:1.19-1.30, P<0.001), 9% (Adjusted RR:1.09; 95% CI:1.02-1.16, P=0.007) and 43% (Adjusted RR: 1.43; 95% CI:1.34-1.52, P<0.001) increase in total, cardiac, and non-cardiac hospitalization days post-AMI respectively, after adjusting for baseline patient and hospital characteristics. Depressive-associated increases in cardiac health service consumption were significantly more pronounced among patients of lower than higher cardiac risk severity. The disproportionately higher cardiac health service consumption among lower-risk AMI depressive patients may suggest that health seeking behaviors are mediated by psychosocial factors more so than by objective measures of cardiovascular risk or necessity. Third, methodological issues related to missing data were explored. A systematic review of three psychiatric journals revealed that a small minority of studies (5.8%) addressed the impact of missing data in a meaningful way. An example using real data demonstrated the potential bias introduced by missing data and different ways to address this bias. The paper concludes with recommendations for both reporting and analyzing studies with substantial amounts of missing data. Overall, the studies add to the literature exploring the relationship between depression and outcomes following acute myocardial infarction. Future studies measuring the relationship between depression and mortality will need to factor the mediating relationship between depression and cardiac functional status. The increased health service utilization associated with depression will need to be replicated in other illness models. Together, the studies add to the existing conceptual framework for measuring relationships between depression and outcomes in patients with cardiovascular illnesses.

PhD

Advisors/Committee Members: Goering, Paula N., Health Policy, Management and Evaluation.

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Introduction: Using an animal model, we examined weight gain in rats exposed to olanzapine, as well as whether increased weight was associated with food intake, visceral fat and/or locomotion. Methods: Sprague-Dawley rats were chronically treated with olanzapine while being offered diets including standard chow, a high fat (60% fat) diet, and a high fat/high carbohydrate (42% fat; 42.7% carbohydrate) diet. Body weight, food intake, visceral fat and locomotor activity were measured. Results: Our findings related to weight gain are in line with other reports indicating that while olanzapine-induced weight gain can be observed, it does not mirror what is observed in humans on two levels: (i) it is not of the same magnitude, and (ii) it is more gender specific i.e., females greater than males. Conclusions: These data confirm that chronic treatment with olanzapine has varying effects on weight gain, food intake, visceral fat and locomotor activity.

MAST

Advisors/Committee Members: Remington, Gary, Medical Science.

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Depression is commonly associated with abnormal sleep architecture. This thesis undertook to assess sleep architecture as a biological correlate of self and observer-rated depressive state, and consists of three studies. The first used a categorical approach to examine the association of sleep architecture with subjective mood in a community sample of 74 preoperative patients, and found no association between high depression scores and hypothesized sleep markers. The second followed 16 patients with Major Depression who were treated with the antidepressant mirtazapine in an 8 week longitudinal study during which they underwent polysomnography on 6 occasions. It was found that classes of sleep markers (REM latency or REM, arousal index, and slow wave sleep) tend to predict response when analyzed concurrently. The third study was methodological in nature, and found that commercially available software for automating eye movement counts did not show strong correspondence with visually scored polysomnographic data.

MAST

Advisors/Committee Members: Shapiro, Colin M., Cell and Systems Biology.