This study examined the effects of 30 minutes of cycle exercise at 65% V̇O2max on the pharmacokinetics of the S.S.R.I. sertraline. Blood samples were taken over 48 hours from 14 healthy males (23.9±2.5 years, 80.3±12.6 kilograms) following oral ingestion of a single 100 mg dose of sertraline. Participants completed two sertraline trials separated by at least two weeks; one trial while resting and the other trial with exercise as described above. With exercise, the absorption rate constant and volume of sertraline in the central compartment decreased, while the elimination half-life increased. Maximum concentration, time of maximum concentration, and area under the curve were unchanged. Fitness level had little impact on the concentration of sertraline, as compartmental modeling was unchanged when relative V̇O2max was added as a covariate. However, controlling for participant body weight improved the model estimate. These results indicate that acute aerobic exercise has the potential to change the concentration of sertraline in vivo.

This study explores the lived experiences of six Canadian Chinese-White heterosexual couples throughout their relationship lifespans. Interethnic coupling of this ethnic/racial configuration is on a steady rise, and mental health professionals can expect to find themselves working with this population in increasing numbers. In light of Canada’s unique history, ethnic distribution, and official policy of multiculturalism, it adds a much needed perspective to the vast majority of studies that focus on Black-White couples in an American context. Grounded in a constructivist-interpretive paradigm, this study uses narrative inquiry to arrive at six distinctive narratives, each with their central themes and a relationship life map to situate lived experiences in time, place, and forms of interaction. An across-narratives analysis was subsequently performed to identify overarching themes and subthemes across the six narratives. The findings suggest that couples shared similar experiences around their families; feelings of compatibility; and cultural differences around religion, food, and language. Further, they shared their insights on relationship maintenance processes with respect to the maintenance of family cohesion and management of differences. Overall findings in this study were consolidated to generate a co-constructive, contextualized, and strength-based model to understanding the lived experiences of Canadian Chinese-White heterosexual couples. This conceptual model is a response to the traditionally problem-focused literature on interethnic couple relationships, situates lived experiences in the multilayered contexts in which they are embedded, and highlights couples’ innate abilities to co-construct a relational narrative that embodies their shared realities and insights and sense of “we-ness.” Clinical applications of the conceptual model are discussed, along with limitations associated with this study and recommendations for future research.

This thesis is divided into three texts. The first is a compendium, which situates the major themes of the second text (a fictitious novel) into a scholarly context and delves into the broader academic questions that arise from it regarding the treatment and care of people with special needs. Those themes are put into a context that enables special education teachers to expand thier notions about communicating with and understanding their autistic and special needs students. It not only examines my own autobiographical connection to the novel (by the fact that I have a sister with a combination of Down Syndrome and autism) but also extends the themes into a broader context, and looks at typical expectations in families with mentally handicapped members and the various methods and approaches of communicating with them. The third text elaborates on specific aspects of these themes in an endnote format.

This thesis is divided into three texts. The first is a compendium, which situates the major themes of the second text (a fictitious novel) into a scholarly context and delves into the broader academic questions that arise from it regarding the treatment and care of people with special needs. Those themes are put into a context that enables special education teachers to expand thier notions about communicating with and understanding their autistic and special needs students. It not only examines my own autobiographical connection to the novel (by the fact that I have a sister with a combination of Down Syndrome and autism) but also extends the themes into a broader context, and looks at typical expectations in families with mentally handicapped members and the various methods and approaches of communicating with them. The third text elaborates on specific aspects of these themes in an endnote format.

Intracellular calcium and oxidative stress dyshomeostasis, which can be highly interactive, occur in bipolar disorder (BD), but the pathogenesis of these disturbances is unknown. The transient receptor potential (TRP) melastatin subtype 2 (TRPM2) and canonical subtype 3 (TRPC3) calcium-permeable non-selective ion channels, already implicated in BD, are involved in calcium and oxidative stress signalling. Thus, I sought to determine whether the expression and function of these channels are modulated by oxidative stress exposure in rat cortical neurons, astrocytes, and in human B lymphoblast cell lines (BLCLs), a cell model that reports diagnostically relevant abnormalities in BD. This thesis work demonstrated that TRPC3 expression and function are decreased after chronic, but not acute oxidative stress exposure in both human and rat cell models. TRPM2 expression, on the other hand, was increased after both acute and chronic stressor treatments in rat cortical neurons. In BLCLs, TRPM2-mediated calcium entry was blunted although no difference in TRPM2 mRNA expression was detected. Moreover, BLCLs from BD-I patients exhibited greater susceptibility to cell death and a differential sensitivity of TRPM2-mediated calcium influx to acute oxidative stress compared with healthy subjects, further supporting reduced cellular resilience in the pathophysiology of BD-I. I also demonstrated that TRPC3 protein is expressed in human brain from 8 days to 83 years old supporting an ongoing role in the developing and adult human brain. These findings support an important role for TRPM2 and TRPC3 in sensing and responding to oxidative stress, and in transducing oxidative stress signalling to intracellular calcium homeostatic and cellular stress responses, which have been implicated in the pathophysiology of BD. Finally, this work has highlighted an inherent difference in TRPM2 channel functionality in BD type I subjects compared with controls, adding functional evidence to the genetic and differential expression findings implicating TRPM2 dysfunction in BD.

Chronic major depressive disorder (CMDD) is a common and debilitating illness. Its pathophysiology needs further elucidation, before more effective targeted treatments can be developed for this condition. To gain a better understanding of the psychobiology of CMDD, three interconnected studies were conducted that examined the interplay between chronic depression, cortisol responses, and personality. Study 1 examined cortisol responses to the Trier Social Stress Test (TSST) in CMDD participants (n=29) as compared to healthy controls (n=28). It was hypothesized that cortisol responses would be greater in the CMDD population. Results indicated that females with CMDD had increased cortisol output compared to female controls, a pattern consistent with the hypothesis. However, males with CMDD had decreased cortisol responses compared to male controls. These results suggest that cortisol responses to social stress are altered in those with CMDD; however, females and males experience fundamentally different changes. Study 2 examined moderating effects of personality on cortisol responses to the TSST in those with CMDD (n=51) as compared to healthy controls (n=57). It was hypothesized that higher neuroticism and/or lower extraversion would be associated with increased cortisol responses in CMDD participants. As hypothesized, lower extraversion was associated with increased cortisol reactivity in those with CMDD but not in healthy controls. However, no association was found between neuroticism and cortisol responses. These findings could support the notion that lower extraversion is a vulnerability marker for chronic depression and thus a possible target for treatment. Study 3, evaluated the cortisol awakening response (CAR) in CMDD participants (n=27) compared to healthy controls (n=30). It was hypothesized that such awakening responses would be more pronounced in the depressed population compared to controls. Contrary to expectation, no differences were found between the groups. However, lower extraversion was associated with a lower CAR in both CMDD and healthy controls, a finding that was not anticipated a priori. These interconnected studies suggest that examining relationships between depression, cortisol responses, and personality, can assist with identifying distinct psychobiological profiles in those with chronic depression. It is proposed that this strategy will improve the likelihood of developing more targeted treatments for this population.

The purpose of this study was to explore the relationship between the formalization of inter-organizational partnerships and collaboration among staff members working together across primary care, mental health and addition organizations to provide services to adults with complex mental health and addiction needs. Phase I of the study provided an environmental scan of existing partnerships among Family Health Teams (FHTs) and Community Health Centres (CHCs), and the Mental Health and/or Addiction (MHA) organizations they partner with, in the province of Ontario (Canada). Phase II explored the relationship between formalization and a) administrative collaboration and b) and service delivery collaboration. The hypotheses proposed that staff members who are part of formalized partnerships would report higher levels of collaboration. Phase III explored how formal and informal partnerships and collaboration are experienced by the administrative and service provider staff members who work across FHTs, CHCs and MHAs organizations. Using a mixed methods approach, data were collected using electronic surveys and telephone interviews. The results of Phase I indicated that FHTs and CHCs in Ontario have between 1-3 partnerships with MHA organizations. Most are informal partnerships, have existed for less than 5 years, and most staff members (partners) interact on a monthly basis. The quantitative results of Phase II showed no significant relationship between formalization and either form of collaboration. The qualitative findings from Phase III provide two key contributions. First, the results of the interviews may help explain why collaboration was not higher in formalized partnerships, as demonstrated by the range of advantages and disadvantages experienced by administrators and service providers in both formal and informal partnerships. Second, the findings illuminate factors related to the process of creating and/or formalizing partnerships, suggesting that there may be other factors that mediate or have a direct impact on the relationship between formalization and collaboration. By bringing together the study findings, the study addresses a gap in the literature by proposing a pathway through which formalization may be associated with collaboration. The results of the study provide opportunities for future research to help improve the quality and accessibility of services to adults with complex mental health and addiction needs.

Chronic major depressive disorder (CMDD) is a common and debilitating illness. Its pathophysiology needs further elucidation, before more effective targeted treatments can be developed for this condition. To gain a better understanding of the psychobiology of CMDD, three interconnected studies were conducted that examined the interplay between chronic depression, cortisol responses, and personality. Study 1 examined cortisol responses to the Trier Social Stress Test (TSST) in CMDD participants (n=29) as compared to healthy controls (n=28). It was hypothesized that cortisol responses would be greater in the CMDD population. Results indicated that females with CMDD had increased cortisol output compared to female controls, a pattern consistent with the hypothesis. However, males with CMDD had decreased cortisol responses compared to male controls. These results suggest that cortisol responses to social stress are altered in those with CMDD; however, females and males experience fundamentally different changes. Study 2 examined moderating effects of personality on cortisol responses to the TSST in those with CMDD (n=51) as compared to healthy controls (n=57). It was hypothesized that higher neuroticism and/or lower extraversion would be associated with increased cortisol responses in CMDD participants. As hypothesized, lower extraversion was associated with increased cortisol reactivity in those with CMDD but not in healthy controls. However, no association was found between neuroticism and cortisol responses. These findings could support the notion that lower extraversion is a vulnerability marker for chronic depression and thus a possible target for treatment. Study 3, evaluated the cortisol awakening response (CAR) in CMDD participants (n=27) compared to healthy controls (n=30). It was hypothesized that such awakening responses would be more pronounced in the depressed population compared to controls. Contrary to expectation, no differences were found between the groups. However, lower extraversion was associated with a lower CAR in both CMDD and healthy controls, a finding that was not anticipated a priori. These interconnected studies suggest that examining relationships between depression, cortisol responses, and personality, can assist with identifying distinct psychobiological profiles in those with chronic depression. It is proposed that this strategy will improve the likelihood of developing more targeted treatments for this population.

Intracellular calcium and oxidative stress dyshomeostasis, which can be highly interactive, occur in bipolar disorder (BD), but the pathogenesis of these disturbances is unknown. The transient receptor potential (TRP) melastatin subtype 2 (TRPM2) and canonical subtype 3 (TRPC3) calcium-permeable non-selective ion channels, already implicated in BD, are involved in calcium and oxidative stress signalling. Thus, I sought to determine whether the expression and function of these channels are modulated by oxidative stress exposure in rat cortical neurons, astrocytes, and in human B lymphoblast cell lines (BLCLs), a cell model that reports diagnostically relevant abnormalities in BD. This thesis work demonstrated that TRPC3 expression and function are decreased after chronic, but not acute oxidative stress exposure in both human and rat cell models. TRPM2 expression, on the other hand, was increased after both acute and chronic stressor treatments in rat cortical neurons. In BLCLs, TRPM2-mediated calcium entry was blunted although no difference in TRPM2 mRNA expression was detected. Moreover, BLCLs from BD-I patients exhibited greater susceptibility to cell death and a differential sensitivity of TRPM2-mediated calcium influx to acute oxidative stress compared with healthy subjects, further supporting reduced cellular resilience in the pathophysiology of BD-I. I also demonstrated that TRPC3 protein is expressed in human brain from 8 days to 83 years old supporting an ongoing role in the developing and adult human brain. These findings support an important role for TRPM2 and TRPC3 in sensing and responding to oxidative stress, and in transducing oxidative stress signalling to intracellular calcium homeostatic and cellular stress responses, which have been implicated in the pathophysiology of BD. Finally, this work has highlighted an inherent difference in TRPM2 channel functionality in BD type I subjects compared with controls, adding functional evidence to the genetic and differential expression findings implicating TRPM2 dysfunction in BD.

Resilience and post trauma responses often coexist, however, for the past decades, the trauma paradigm has served as the dominant explanatory framework for human suffering in post-conflict environments, while the resilience of individuals and communities affected by mass violence has not been given equal prominence. Consequently, mental health interventions in post-conflict zones often fail to respond to local realities and are ill equipped to foster local strengths. Drawing primarily from trauma, feminist and structural violence theories, this study strengthens understanding of adult resilience to traumatic exposure by examining the resilience of Quechua women in the aftermath of the political violence in Peru (1980-2000), and their endurance of racially and gender-targeted violence. The study uses a cross sectional survey to examine the resilience and posttraumatic responses of 151 Quechua women. Participants were recruited from an urban setting and three rural villages in Ayacucho, Peru. The study examines the associations between resilience, past exposure to violence, current life stress and post-trauma related symptoms as well as the individual and community factors associated with the resilience of Quechua women. In doing so, this study makes a unique contribution by simultaneously examining posttraumatic responses and resilience in a post-conflict society, an area with a dearth of research. Results indicate that resilience was not associated with overall posttraumatic stress related symptoms, but instead higher resilience was associated with lower level of avoidance symptoms and therefore with lesser likelihood of chronic symptoms. Findings also demonstrate that enhanced resilience was associated with women’s participation in civic associations, as well as being a returnee of mass displacement. Lower resilience was instead associated with lower levels of education, absence of income generated from a formal employment and the experience of sexual violence during the conflict. These results were triangulated with qualitative findings, which show that work, family, religion, and social participation are enhancing factors of resilience. The study highlights the courage and resilience of Quechua women despite persistent experiences of everyday violence. The importance to situate trauma and resilience within historical processes of oppression and social transformation as well as other implications for social work practice and research are discussed.