Only thirty known species have populations at high latitudes in both hemispheres, this is, a bipolar distribution. Five of them belong to the genus Carex. Before attempting to elucidate the origins of such distributions, we need to resolve taxonomical problems that are typically encountered in such species. We focus on the Carex capitata complex, which includes Carex arctogena as a bipolar species, in worldwide scope sampling. A morphometric study and phylogenetic analyses based on maximum parsimony, Bayesian inference and Statistical Parsimony have revealed: a) C. capitata and C. arctogena are different species; b) C. anctarctogena is a synonym of C. arctogena and c) a great biodiversity previously undetected in western North America that could lead to the description of three new taxa (“Carex cayouetteana”, Carex sp. nov. 1 and 2) comprised in the so called “C. cayouetteana” lineage. More studies are needed in some C. capitata samples from Russia that appears in the molecular analyses in a strongly supported clade.

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.

Evidências sugerem o envolvimento de mecanismos de resiliência celular, estresse e de alterações epigenéticas na patofisiologia dos transtornos de humor, como o transtorno bipolar (TB) e o transtorno depressivo maior. Os estudos apresentados nesta tese tiveram como objetivo explorar esses mecanismos de forma translacional, partindo da avaliação da morte e sobrevivência celular até a correlação dos achados com a resposta ao tratamento. O primeiro capítulo se propôs a revisar dados da literatura com relação à progressão do TB, os quais apontam para uma série de alterações biológicas envolvendo resiliência celular em pacientes com diferentes estágios do transtorno. O segundo capítulo teve como objetivo avaliar parâmetros de morte celular em pacientes com TB, onde um aumento na frequência de células em apoptose inicial foi detectado em comparação a controles. Em seguida, considerando os efeitos potenciais dos glicocorticóides na indução de apoptose, o terceiro capítulo avaliou a atividade do eixo hipotálamo-pituitária-adrenal (HPA) em pacientes com TB, seus irmãos e em controles saudáveis, além de mecanismos moleculares associados ao eixo. Nossos resultados sugerem uma disfunção do eixo HPA em pacientes associada a uma hiporresponsividade do receptor de glicocorticóide, maiores níveis da proteína ligante de FK506 de 51 kDa (FKBP51) e um aumento da metilação do gene FKBP5. Nós ainda observamos que os pacientes com maior número de episódios apresentaram uma disfunção do eixo mais pronunciada do que aqueles em estágio inicial. No quarto e último capítulo nós realizamos um estudo para verificar os mecanismos moleculares pelos quais o estresse pode induzir alterações epigenéticas envolvendo a metilação do DNA, onde descrevemos o efeito oposto das cochaperonas FKBP51 e FKBP52 sobre a fosforilação da enzima DNA metiltransferase 1 (DNMT1). Além disso, a redução da fosforilação da DNMT1 correlacionou-se com uma melhor resposta clínica ao tratamento em pacientes com transtorno depressivo maior. Em suma, os resultados desta tese sugerem que a resiliência celular, a resposta ao estresse e a metilação do DNA desempenham importantes papéis na patofisiologia, progressão e resposta ao tratamento de pacientes com transtornos de humor. Novos tratamentos com alvo em mecanismos epigenéticos, na modulação do receptor de glicocorticóide e no aumento da resiliência celular devem ser priorizados em estudos futuros. / Evidence suggests the involvement of cellular resilience mechanisms, stress, and of epigenetic alterations in the patophysiology of mood disorders, such as bipolar disorder (BD) and major depressive disorder. The studies presented in this thesis aimed at exploring these mechanisms in a translational fashion, going from the assessment of cellular death and survival to the correlation of findings with the response to treatment. The first chapter aimed at reviewing data from the literature regarding the progression of BD, which point to a series of biological alterations involving cellular resilience in patients at different stages of the disorder. The second chapter aimed at assessing cell death parameters in patients with BD, in which a higher frequency of cells in early apoptosis was detected when compared to controls. In addition, considering the potential effects of glucocorticoids in the induction of apoptosis, the third chapter assessed the activity of the hypothalamus-pituitary-adrenal (HPA) axis in patients with BD, their siblings, and in healthy controls, in addition to the molecular mechanisms associated with the axis. Our results suggest a dysfunction of the HPA axis in patients associated with a hyporesponsiveness of the glucocorticoid receptor, increased FK506-binding protein of 51 kDa (FKBP51) levels, and increased methylation levels at the FKBP5 gene. We also noted that patients with a greater number of previous episodes presented a more pronounced dysfunction of the axis when compared to early-stage patients. In the fourth and last chapter we performed a study to verify the molecular mechanisms by which stress can induce epigenetic alterations involving DNA methylation, where we describe opposing effects of the cochaperones FKBP51 and FKBP52 on DNA methyltransferase 1 (DNMT1) phosphorylation. In addition, the reduction of DNMT1 phophorylation was correlated with a better clinical response to treatment in patients with major depressive disorder. In summary, the results of this thesis suggest that cellular resilience, response to stress and DNA methylation play key roles in the pathophysiology, progression and response to treatment in patients with mood disorders. Novel treatments targeting epigenetic mechanisms, the modulation of the glucocorticoid receptor, and enhancing cellular resilience should be prioritized in future studies.

No description available.

If mania and depression are part of the same pathological processes, one would predict that episodes of one prospectively increase the odds of episodes of the other. The aim of the present study was to test this hypothesis. For comparison purposes, their relationship was contrasted to the relationship between mania and periods of psychosis. Exploratory analyses also tested the degree to which episodes of each occur with greater frequency over time (i.e., kindling). Participants for the present study came from the Suffolk County Mental Health Project (N = 628), a study of first-admission patients with psychosis. Of these participants, 144 met diagnostic criteria for bipolar I disorder and were analyzed for the current study. Results indicated that mania in a given month predicted depression the following month, even after controlling for other symptoms. The reverse, however, was not the case. Mania and psychosis, in contrast, were found to be robust predictors of one another from month to month. Effects were not due to treatment or demographic differences. These findings provide evidence that mania and depression are weakly related. In contrast, mania and psychosis are more closely linked. Findings are consistent with suggestions that psychiatric nosology regroup mania more closely with thought disorders rather than with internalizing or depressive ones. They also alert clinicians to the strong, longitudinal persistence and comorbidity among these syndromes.

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)