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.

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.

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.

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.

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.

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.

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.

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

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.

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