Daily rhythms of physiology and behaviour in mammals are orchestrated by a hierarchical network of cellular oscillators. The master pacemaker that defines local and systemic timing across the brain and body are the suprachiasmatic nuclei of the hypothalamus (SCN). Disruption to the timing of sleep and daily behavioural activity can manifest in a range of pathologies including neuropsychiatric disorders. Bipolar disorder (BPD) is once such neurological condition that exhibits profound associations with altered circadian rhythm generation and whose toolkit of pharmacological interventions impact upon circadian rhythm generation. Currently it is unclear exactly how changes to rhythmic physiology contribute to the aetiology and pathology of BPD. In recent years, rodent models possessing lesions within genes that make up the basic cellular oscillator are widely reported to exhibit concomitant changes in affective behaviours, namely mania-like phenotypes. Recently a mouse model possessing a mutation within the neuron-specific Na+/K+-ATPase (NKA) alpha3 subunit, known as Myshkin, was described as a model of the manic phase of BPD. The NKA alpha3 is not reported as a critical element of the circadian oscillator and we used this opportunity to characterise the behavioural and physiological circadian system of these animals. Under wheel-running paradigms Myk/+ animals exhibited a broad array of behavioural deficits including lengthened, low amplitude and labile free-running rhythms, altered phase re-setting and elevated metabolic activity. Physiological characterisation of the SCN revealed deficits in amplitude of electrical output and changes to post-synaptic signalling although the ex vivo molecular pacemaking of the SCN remained intact. Myshkin animals therefore represent a novel model in which changes to central output arise independently of changes to basic molecular pacemaking. Despite this seemingly distinct mechanism Myshkin animals share many mood and circadian phenotypes with other clock gene models of affective behaviours highlighting that changes to pacemaking output of the SCN may be a critical factor across animal models exhibiting circadian and mood deficits. In addition, the impact of the mood stabiliser lithium, commonly prescribed in BPD, on cellular pathways within the SCN was investigated. Lithium consistently lengthens the period of cellular and behavioural rhythms in mammals although the mechanism of this action is yet undefined. Glycogen synthase kinase 3β (GSK3β) and inositol monophosphatase (IMPase) are the major biochemical targets of lithium at therapeutic concentrations. GSK3β is known to shorten rhythms and this study targeted IMPase and inositol phosphate turnover in the period lengthening effects of lithium. We reveal that although inhibition of IMPase dampens SCN molecular rhythms, the period of oscillations remains unchanged and therefore lithium acts upon distinct cellular pathways within the SCN to exert effects on period.

Class of 2009 Abstract / Objectives: This study utilized a prescription claims database to retrospectively assess the relationship between adherence rates with a mood stabilizer in bipolar type I patients for: gender, age, psychiatric hospitalization rates, cost of services, and concomitant psychotropic medications. Methods: Adult patients with bipolar type I disorder (N=149; F=92 and M=57) who received at least two prescriptions of a mood stabilizer (i.e., carbamazepine, lamotrigine, lithium, oxcarbazepine, and valproic acid) during a 3-month intake period were included. Adherence to the mood stabilizer was retrospectively analyzed using high: >75% (> 274 days) vs. low: < 75% (< 274 days) supply of a mood stabilizer during 12-months. Results: Only 35.6% of the patients (N=53) met the criteria for > 75% adherence and 11.4% (N=17) met the criteria for > 90% adherence. There was a trend toward women having more days supply of a mood stabilizer compared to men (p=0.08) and older patients having a higher adherence rate with a mood stabilizer (p=0.06). The high adherence group had greater prescription costs (p<0.001) and total cost per year (R2=0.34, p=0.064) and more concomitant medications (p=0.04) than the low adherence group. Overall, there were no significant differences between the high and low adherence groups for mean hospital days, inpatient costs, and total cost of care. Among those patients that were hospitalized there was a negative correlation between adherence and inpatient cost (R2=0.49, p=0.024). Conclusions: Our findings suggest that patients with bipolar type I disorder demonstrate poor medication adherence with a mood stabilizer and that adherence rates based on a prescription claims database using two adherence categories may not be a predictive factor for psychiatric hospitalizations or cost of care.

Bipolar disorder is a serious mental disorder, affecting anywhere from 2 to 4 percent of Americans. Though research has indicated that this disorder can be devastating for patients, less is known about how the disorder impacts family members. There is no research that has considered impacts on family members adjusting to college. The purpose of the current study was to determine the extent to which having a family member with bipolar disorder impacts adjustment to college, as well as factors that might account for worse functioning. Two groups were recruited: students with a bipolar family member (n = 25) and students with no family history of the disorder (n = 50). Participants were interviewed regarding their own histories of a mood disorder, as well as mood disorder histories in their immediate families. They then completed surveys assessing adjustment to college, functioning, caregiving burden, parental relationship, and attachment style. Students with a family history of bipolar disorder had significantly lower social adjustment scores, lower personal-emotional adjustment scores, and lower financial functioning scores than students without this history. Lower scores were found even after controlling for psychopathology. Avoidant attachment behaviors, anxious attachment behaviors, and aspects of the paternal relationship were identified as potential mediators. Caregiving burden was identified as a partial mediator. Implications for families and educational institutions are discussed.

No description available.

Objective: Phenomenological and treatment differences between children and adolescents with bipolar I disorder in a public mental health system were examined. Method: A systematic medical record review was performed on a sample of 83 patients, focusing on documented DSM IV symptoms of mania or depression, attention deficit hyperactivity disorder, conduct disorder, schizophrenia, and post-traumatic stress disorder. Cross-tabulation and logistic regression analyses were performed comparing the presence/absence of symptoms for each disorder and treatments provided for children and adolescents. Results: Prepubertal patients were significantly more likely to be male, easily distracted, inattentive, detached from others, hyper-vigilant, prescribed stimulant medication, and to meet the diagnostic criteria for attention-deficit/hyperactivity disorder or Conduct Disorder than adolescents. Conclusions: Consistent with the published literature, phenomenological differences between children and adolescents are present and being recognized for differential diagnosis and treatment by community practitioners. More attention to documenting some cardinal symptoms of mania, the persistence of bipolar symptoms, and the nature of cycling for those with mixed states is needed.

Magister Artium - MA / My MA mini-thesis in Creative Writing is a collection of 33 poems titled Learning to Exhale. The poems are centred around a character – a black African woman who is sharing her experiences of mental illness. The poems revolve around memory, forgetting and remembering; going back to the moment when the woman realises that she is ill, understanding it from the present while working to find ways to express what bipolar disorder is and how she experiences it. The collection also highlights her search for words and meaning to describe these experiences that are highly traumatic. This is to create a language of expressing the indescribable. This means that the form and structure is experimental, combining differing styles and form to show different voices, different states of mind that swing from depression, mania to suicidal thoughts.

Individuals who experience bipolar disorder may have difficulty acquiring and maintaining relationships due to the stigma associated with mental illness. The purpose of this generic qualitative study was to examine the attitudes and perceptions of African American men and women regarding their experiences of dating and relationships with individuals who suffer from bipolar disorder. The theory used in this study was equity theory. The research question for this study explored how African American adults experience relationship acquisition and maintenance with a partner who has been diagnosed with bipolar disorder. For this generic qualitative study, there were 12 respondents. Participants were African American adults who had dated or been in a relationship with an individual diagnosed with bipolar disorder. Themes that emerged from this study were sense of relief, sense of fear, unmodified affection, benefits of the relationship, resolution of unfair situations, reluctance to participate in a relationship with an individual diagnosed with bipolar disorder again, and race intensified the relationship. The participants associated acquisition, or the early stages of the relationship, with challenges, especially if they were unaware of the diagnosis in the beginning and could not explain certain behaviors. The results of this study can be used to promote understanding about bipolar disorder and the impact of mental illness on relationships.

No description available.

Large-scale transcriptomic studies are among of the most comprehensive accounts we have of the biological processes underlying human brain development and ageing. However, many analyses and descriptive models applied to gene expression data implicitly assume that developmental change is continuous and uninterrupted. Perhaps this bias is often overlooked because the emphasis is on what is changing during development rather than how development itself is changing. Indeed, despite the richness of transcriptomic data and its capacity to recapitulate higher-order functions, few have used it to understand the dynamics of brain development. Gene expression is determined by complex, high-dimensional interactions of the gene regulatory network. Dynamic systems theory states that the interactions of components in any complex systems will converge on certain stable patterns, also known as attractor states. To approximate these stable states, the current study leveraged robust and sparse k-means clustering to identify tissue samples with similar patterns of gene expression across the transcriptome. Sample ages were then used to visualize when in developmental time these stable patterns are present. The resulting model describes the developmental dynamics of the brain transcriptome as a series of non-linear, overlapping states that progress across the lifespan. / Thesis / Master of Science (MSc)

Background: The objective of this thesis was to measure oxidative stress (OS) in women with Bipolar Disorder (BD) who used combined oral contraceptives (OCU). Based on our literature review, it was predicted that OCU would increase OS levels relative to non-contraceptive users (NCU) in women. Methods: Thirty-five participants (BD n=25; Control n=10) were recruited from an ongoing study based in British Columbia ‘The Systematic Treatment Optimization Program in Early Mania.’ Participants were administered psychological screening tools (Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale, Mini International Neuropsychiatric Interview and Hamilton Depression Rating Scale) and provided a blood sample for the assays (Lipid Hydroperoxide (LPH), Protein Carbonylation, 4-Hydroxynonenal, 3-Nitrotyrosine (3-NT) and 17-Beta Estradiol). Results: In our primary analysis we did not find differences in OS between BD and controls relative to OCU. Within our remaining analyses, only BD women (n=17) and who gave smoking status were included. We found 3-NT to be increased in OCU compared to NCU (F (1, 12) = 5.639, p = 0.035). With respect to mood stabilizer use, 3-NT was increased in OCU relative to NCU (F (1, 10) = 6.33, p=0.031). As for atypical antipsychotics, 3-NT was heightened in OCU adjunctive users compared to NCU who did not use atypical antipsychotics (F (3, 10) = 4.822, p = 0.025). As for our correlation analyses, YRMS correlated with 3-NT and LPH in OCU BD women (r(11)= 0.711, p=0.014 and r(11) = 0.676, p=0.022, respectively) and 17-Beta Estradiol correlated with LPH (r(17) = 0.598, p = 0.001). Our results are preliminary and are limited by our small sample size and various other factors (i.e. controls). Conclusion: The association between hormones and oxidative stress still remains controversial. Here we showed, after controlling for smoking, BMI and age the use of a COC significantly increased 3-NT in women with BD. Moreover, hormones may influence the relationship between OS and mood episodes. / Thesis / Master of Science (MSc)