Parents raising children with Attention-deficit/hyperactivity disorder (ADHD) experience high levels of parenting stress, especially when ADHD is accompanied by comorbid Oppositional Defiant Disorder (ADHD/ODD). Children with ADHD experience difficulties with their executive functions in such areas as inhibition control, working memory, and emotional regulation. Despite evidence linking ADHD with parenting stress, and ADHD with executive function difficulties (EFDs), there is little research exploring whether EFDs within an ADHD population are associated with parenting stress. This dissertation’s main objective is to determine whether parent-reported and teacher-reported childhood EFDs are associated with elevated levels of parenting stress. A secondary data analysis was completed on a cross-section of parent and teacher completed psychiatric assessment measures for children (n=243) diagnosed with ADHD. Measures included the Behavior Rating Inventory of Executive Function, the Conners’ Parent Rating Scale and the Parenting Stress Index, Long Form. A number of important findings were produced; key of which was the finding that a strong association exists between parent-reported EFDs and Child Domain parenting stress. Consistent with prior ADHD research, difficulties with emotional control and inhibition were found to be potent predictors of Child Domain parenting stress. To a lesser degree, children’s difficulties with initiation and self-monitoring were associated with Child Domain parenting stress, suggesting that daily hassles pose challenges for parents, especially when the child attends a new school. Also important was the finding that parent-reported oppositionality partially mediated the relationship between EFDs with emotional control, inhibition and shift, and Child Domain parenting stress. Despite teachers’ reports that children displayed more severe behaviours than were reported by parents, teacher-reported EFDs were not significantly associated with Child Domain parenting stress, with a few exceptions. Although not a well-explored concept within the literature on ADHD and parenting stress, parental acceptance of the child emerged as source of Child Domain parenting stress and a potential focus for assessment and treatment. Findings from the current study suggest that early identification and intervention with emotional control difficulties and ODD are vital due to their strong association with clinically significant levels of Child Domain parenting stress.

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.

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.

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.

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.

Introduction: This thesis examined the impact of PTSD with Major Depressive Disorder on PTSD severity among Toronto Transit Commission employees who were exposed to a workplace traumatic event, and also the predictors of PTSD severity, mental health treatment seeking, and return to work over the six month study period. Methods: This study utilized data that was collected prospectively from the APT study participants. Information about Axis-I diagnosis and PTSD severity were collected from the SCID-I and the Modified PTSD Symptom Scale respectively. Results: PTSD without MDD (N=29) and PTSD with MDD (N=37) groups were compared. The variables: depression severity (p=0.01), female (p=0.01), non-Caucasian (p=0.01), workplace related stress (p=0.02), and lifetime trauma (p=0.01) significantly predicted PTSD severity. The BPI group significantly predicted mental health treatment seeking (p<0.01) after controlling other variables. Conclusion: This study highlights the substantial risk for experiencing greater PTSD severity after a workplace traumatic event in TTC employees.

Few mental health studies have explored the prevalence of disorders, risk factors, and availability of services in Antioquia, especially in urban children and adolescent populations. However, access studies have never been developed. Despite growing interest in access, researchers, bureaucrats and interest groups have not come to any consensus about which specific factors may be considered in order to improve access for children and adolescents, especially in provinces with high levels of violence, displacement and inequality. This thesis aims to generate such a consensus among a diverse group of mental health stakeholders around Antioquia. Consensus suggests that predisposing, enabling, need and behaviour factors simultaneously influence access. Additionally, social capital is the resource upon which several mental health programs focus for the development and promotion of mental health services. Finally, stakeholders have identified effectiveness criteria that should be used to evaluate their efficacy as a network in order to improve their work.

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.

Introduction: This thesis examined the impact of PTSD with Major Depressive Disorder on PTSD severity among Toronto Transit Commission employees who were exposed to a workplace traumatic event, and also the predictors of PTSD severity, mental health treatment seeking, and return to work over the six month study period. Methods: This study utilized data that was collected prospectively from the APT study participants. Information about Axis-I diagnosis and PTSD severity were collected from the SCID-I and the Modified PTSD Symptom Scale respectively. Results: PTSD without MDD (N=29) and PTSD with MDD (N=37) groups were compared. The variables: depression severity (p=0.01), female (p=0.01), non-Caucasian (p=0.01), workplace related stress (p=0.02), and lifetime trauma (p=0.01) significantly predicted PTSD severity. The BPI group significantly predicted mental health treatment seeking (p<0.01) after controlling other variables. Conclusion: This study highlights the substantial risk for experiencing greater PTSD severity after a workplace traumatic event in TTC employees.

Few mental health studies have explored the prevalence of disorders, risk factors, and availability of services in Antioquia, especially in urban children and adolescent populations. However, access studies have never been developed. Despite growing interest in access, researchers, bureaucrats and interest groups have not come to any consensus about which specific factors may be considered in order to improve access for children and adolescents, especially in provinces with high levels of violence, displacement and inequality. This thesis aims to generate such a consensus among a diverse group of mental health stakeholders around Antioquia. Consensus suggests that predisposing, enabling, need and behaviour factors simultaneously influence access. Additionally, social capital is the resource upon which several mental health programs focus for the development and promotion of mental health services. Finally, stakeholders have identified effectiveness criteria that should be used to evaluate their efficacy as a network in order to improve their work.