O presente estudo avaliou um grupo de pacientes com transtorno do humor bipolar (THB), episódio depressivo, através de uma bateria de testes neuropsicológicos – Dígitos da Escala Wechsler de Inteligência para Adultos, 3ª edição (WAIS-III) e Wisconsin Card Sorting Test (WCST) –, escala de funcionalidade – Functioning Assessment Short Test (FAST) – e escala de sintomas depressivos – Montgomery-Asberg Depression Rating Scale (MADRS) – e o comparou com um grupo de controles saudáveis. Obtiveram-se como resultados déficits cognitivos significativos no grupo dos pacientes com THB, no que se refere à memória imediata e de trabalho e funções executivas, quando comparados aos controles saudáveis. Também se encontrou uma correlação entre funcionalidade, sintomatologia depressiva e déficits na memória de trabalho e funcionamento executivo. Estes achados levantam a hipótese de que as dificuldades cognitivas e sintomas depressivos interferem significativamente no funcionamento laboral, afetivo e social dos pacientes com THB. / The present study evaluated a group of patients with Bipolar Disorder (BD), major depressive episode, through a battery of neuropsychological tests - Digits of the Wechsler Intelligence Scale for Adults, 3rd edition (WAIS-III) and Wisconsin Card Sorting Test (WCST) - scale functionality - Functioning Assessment Short Test (FAST) - and scale of depressive symptoms - Montgomery-Asberg Depression Rating scale (MADRS) - and compared with a group of healthy controls. Results were obtained as significant cognitive deficits in the patients with BD, with regard to the immediate and working memory and executive functions compared to healthy controls. We also found a correlation between functionality, depressive symptoms and deficits in working memory and executive functioning. These findings raise the hypothesis that the cognitive and depressive symptoms significantly interfere with work functioning, affective and social development of BD patients.

O presente estudo avaliou um grupo de pacientes com transtorno do humor bipolar (THB), episódio depressivo, através de uma bateria de testes neuropsicológicos – Dígitos da Escala Wechsler de Inteligência para Adultos, 3ª edição (WAIS-III) e Wisconsin Card Sorting Test (WCST) –, escala de funcionalidade – Functioning Assessment Short Test (FAST) – e escala de sintomas depressivos – Montgomery-Asberg Depression Rating Scale (MADRS) – e o comparou com um grupo de controles saudáveis. Obtiveram-se como resultados déficits cognitivos significativos no grupo dos pacientes com THB, no que se refere à memória imediata e de trabalho e funções executivas, quando comparados aos controles saudáveis. Também se encontrou uma correlação entre funcionalidade, sintomatologia depressiva e déficits na memória de trabalho e funcionamento executivo. Estes achados levantam a hipótese de que as dificuldades cognitivas e sintomas depressivos interferem significativamente no funcionamento laboral, afetivo e social dos pacientes com THB. / The present study evaluated a group of patients with Bipolar Disorder (BD), major depressive episode, through a battery of neuropsychological tests - Digits of the Wechsler Intelligence Scale for Adults, 3rd edition (WAIS-III) and Wisconsin Card Sorting Test (WCST) - scale functionality - Functioning Assessment Short Test (FAST) - and scale of depressive symptoms - Montgomery-Asberg Depression Rating scale (MADRS) - and compared with a group of healthy controls. Results were obtained as significant cognitive deficits in the patients with BD, with regard to the immediate and working memory and executive functions compared to healthy controls. We also found a correlation between functionality, depressive symptoms and deficits in working memory and executive functioning. These findings raise the hypothesis that the cognitive and depressive symptoms significantly interfere with work functioning, affective and social development of BD patients.

The aetiology of bipolar disorder remains unclear and investigation to date has focussed largely on bipolar patients. Whilst ultimately of huge value, such studies may also be confounded by current mood or experience of repeated illness episodes or current or past medication; using at-risk samples may bypass some of these problems. The current research therefore assessed the efficacy of the Mood Disorder Questionnaire (MDQ) as a screening tool for vulnerability to bipolar disorder. The MDQ was used with two sets of criteria to identify two sub-groups of medication-naïve young bipolar phenotype subjects who were at risk for bipolar disorder by virtue of experience of mood elevation. Analysis of data from the Student Stress Survey was carried out to characterise the bipolar phenotype. Compared to a control group with no experience of mood elevation, the two bipolar phenotype sub-groups showed a gradient of prevalence of bipolar diagnosis and associated co-morbidity. Behavioural and functional magnetic resonance imaging (fMRI) techniques were employed to investigate emotional processing, decision-making, and sleep and circadian rhythmicity in bipolar phenotype students. Analyses revealed that positive emotional processing biases, disrupted decision-making, and increased activity during sleep were associated with the bipolar phenotype and, therefore, may represent vulnerability markers for bipolar disorder. Finally, a psychopharmacological investigation of quetiapine, which stabilises mood, was carried out in healthy volunteers. One-week quetiapine administration resulted in biases away from both positive and negative emotional stimuli (i.e. a mood-stabilising effect), reduced discrimination between different magnitudes of gains and losses during risky decision-making (consistent with an antidepressant effect), and increased sleep duration. In sum, this research has developed our understanding of vulnerability markers associated with the bipolar phenotype and provided a first step towards uncovering the psychological mechanisms through which quetiapine’s clinical effects may be mediated.

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Recent studies suggest that the neural retinal response to light is compromised in diabetes. Electroretinogram studies suggest that the dim light retinal rod pathway is especially susceptible to diabetic damage. The purpose of this study was to determine whether diabetes alters rod pathway signaling.

Bipolar affective disorder and schizophrenia are highly heritable psychiatric illnesses and the leading causes of worldwide disability. The orbitofrontal cortex (OFC) is a region of the frontal lobe with wide spread connectivity with other brain areas involved in reward, motivation and emotion. Evidence from various neuroimaging, genetic, post-mortem and brain lesion studies suggest that orbitofrontal cortex may play a role in pathophysiology of mental illnesses. This thesis sought to investigate the pathogenesis of major psychiatric illnesses through the investigation of orbitofrontal morphology in schizophrenia and bipolar disorder and through its associations with brain structure and function. Orbitofrontal morphology and its structural and functional associations were examined in healthy controls, patients with schizophrenia or bipolar affective disorder, and those at high genetic risk using functional and structural MRI. In the first study we found that the orbitofrontal type III is more frequent and the orbitofrontal type I is less common in the right hemisphere in patients with schizophrenia while in patients with bipolar disorder type III appears more often in both left and right hemispheres. We then sought to examine the relationship of orbitofrontal morphology to disease risk in a study of 146 people at high risk of developing schizophrenia and 110 people at high risk of developing bipolar disorder. We discovered that in the unaffected high risk groups the orbitofrontal type III predicted the development of later psychiatric illnesses, when combined with anterior cingulate morphology. Finally we showed, in a further study, that OFC morphology was associated with measures of schizotypy, brain structure, brain function and cognition. In conclusion, orbitofrontal morphology is linked to major psychiatric disorder and has significant structural and functional associations. As orbitofrontal sulcogyral patterns are formed in early life a fuller awareness of their relevance to brain function holds out the prospect that we could use such measures as an indicator of vulnerability to the development of illness later in life. This work points to the potential for the foundation of a theory of predictive associations between morphological patterns and the development of psychosis.

Polymer electrolyte membrane fuel cells (PEMFCs) exhibit encouraging potential as an enabling technology for the Hydrogen Economy. Currently an important barrier to commercialization is the cost associated with existing PEMFC materials; this project???s goal was to investigate alternative materials for PEMFC bipolar plates. Conductive thermoplastic materials offer the promise of low density, low cost processing, and inexpensive resins, and were the focus of material development for PEMFC bipolar plate applications. In order to develop a thermoplastic bipolar plate this study utilized the combination of a low cost injection moldable commodity polymer resin, and low cost carbon materials as conductive fillers. The materials selected and tested included; a polypropylene copolymer; acetylene carbon black; Vulcan carbon black; and short carbon fiber. The components were combined in a twin screw extruder and injection molded into samples for testing. The result was a spectrum of composite samples with a range of filler loadings from 0 to 60 wt% and varying filler type ratios. Synergy between the different carbon types was achieved which led to better physical properties, specifically conductivity. The novel blends produced were tested for electrical conductivity, mechanical properties, rheology, microscopy, and actual plates were made and tested in a single cell PEMFC. These trials enabled discussion around the feasibility of the materials with respect to processability, cost, and performance (both in the fuel cell and in potential applications). The most significant results were measured using a composite blend with 54 wt% filler loading and a 1:1:1 filler ratio. Mechanical results achieved 68% and 100% of the industry targets for tensile and flexural strength, respectively. Tensile strength attained 27.7 MPa and flexural strength measured 82.8 MPa. Electrical conductivity results for the same samples varied between the two methods of measurement used. Using a fuel cell industry recommended procedure 2.2 S/cm was achieved and using a four point ASTM measurement technique 12.0 S/cm was reported. These values represent 3% to 12% of the industry target. Actual 16 cm2 fuel cell plates were produced, fuel cell hardware constructed and assembled, and the power output was found to be 51% relative to graphite plates. Thermoplastic bipolar plates for PEMFCs made of composite materials is promising, but optimum filler loading that balances all properties is still required in order to achieve conductivity targets. Nevertheless this study has demonstrated that conductive thermoplastic bipolar plates can be produced via injection molding.

Bipolar disorder is associated with significant social and occupational impairments, as well as increased risk for substance abuse and suicide. More research is needed to identify potential mechanisms associated with vulnerability to the disorder. Previous research has identified altered processing of emotional information in bipolar and bipolar-prone individuals, including attentional biases which appear to differ based on the current affective state of the individual. The current study applied a sensitive measure of attention (i.e., eye-tracking) to assess whether vulnerability to bipolar disorder, as indexed by hypomanic personality traits, would be correlated with biases in attention to emotional facial stimuli, independent of mood state. Hypomanic personality traits were hypothesized to be associated with greater attention to happy and angry faces, as indexed by faster initial orientation, more frequent gazes, and longer gaze duration for these stimuli. Participants completed self-report measures assessing current mood symptoms, positive and negative affect, and hypomanic personality traits. They then completed two tasks assessing attention for emotional faces. The first was an eye-tracking task, which measured latency to first fixation, total gaze duration and total number of gazes for each emotional face category. The second was a spatial cueing task which assessed both attentional engagement with emotional faces, and ability to disengage attention from this material. Hypomanic personality traits were significantly negatively correlated with latency to orient attention to happy faces. A trend toward decreased latency to orient to angry faces with higher hypomanic personality traits was also demonstrated. Hypomanic traits were not correlated with attention to sad faces. Furthermore, hypomanic traits were associated only with differences in initial orientation of attention, not with continued engagement or disengagement. The results of this study suggest that individuals with higher levels of hypomanic personality traits, who are hypothesized to be at greater risk of developing bipolar disorder, are characterized by differences in their initial orientation of attention to positive emotional stimuli, independent of their current mood state. This finding is indicative of biased information processing in individuals with vulnerability to bipolar disorder. Such a bias may have important clinical implications for individuals with a vulnerability to bipolar disorder, as it may represent a mechanism by which vulnerability leads to increased, and at times problematic, engagement with rewarding stimuli.

Background Within the context of developmental psychopathology and the psychological factors associated with the onset of severe mood instability, this thesis proposes that early attachment related interactions underlie the development of reflective functioning and effective emotional regulation necessary for optimal functioning. Both insecure attachment and poor reflective functioning have been linked to various mental disorders in which emotion dysregulation surfaces as a core feature. However, the underlying mechanisms by which these constructs interact to predict increased risk to develop bipolar disorder have yet to be considered. Objectives This project’s objectives were to investigate, through a quantitative cross sectional design, the following questions: 1) In what way are attachment, reflective function and emotion regulation associated with proneness to bipolar disorder? 2) Do reflective functioning, emotion regulation, depression and specific metacognitive patterns mediate the influence of attachment on increased likelihood of developing bipolar disorder? Method An online survey was used to ask 2325 participants to complete questionnaires measuring the variables of hypomanic traits, attachment relationship style, mood, emotion regulation, metacognitive patterns and reflective functioning. The survey was designed to give participants feedback immediately after entry completion, which proved to be a very successful recruitment strategy. For the analysis of the data, structural equation modeling (SEM), multivariate and univariate statistics were used. Results SEM analysis demonstrated that internal dysfunctional emotion regulation is the strongest predictor of bipolar disorder proneness, whilst anxious insecure attachment holds a strong direct relationship with internal dysfunctional emotion regulation not mediated by reflective functioning. Thus, anxious insecure attachment and reflective functioning emerged as indirect predictors to bipolar proneness, being fully mediated by internal dysfunctional emotion regulation strategies, depressive symptoms, perceived well being and negative metacognitive patterns. The use of dysfunctional emotion regulation strategies directly predicted low mood and indirectly predicted decreased well being and increased risk to develop bipolar disorder. Furthermore, in this sample the presence of hypomanic traits alone did not imply proneness to bipolar disorder, but it was the combination of hypomanic traits and depressive symptoms that best predicted increased likelihood of experiencing bipolar disorder. Discussion The results highlight the importance of investigating the underlying mechanisms of severe mood instability. The findings support the manic defense hypothesis, which suggests that manic symptoms emerge to offset underlying depressive mood. It was concluded that severe mood instability emerges and is maintained because of the influence of developmental interpersonal risk factors such as anxious insecure attachment. The latter fosters dysfunctional cognitive features that promote the use of maladaptive emotion regulation strategies, which in turn give rise to depressive mood, diminished well being and ultimately increased risk to develop bipolar disorder. Thus, to better understand and treat bipolar disorder it is important to focus on tackling these psychological aspects of the disorder.

A dissertation submitted to the Faculty of Medicine in part fulfilment of the requirements for the Degree of Master of Medicine in Psychiatry at the University of the Witwatersrand. Johannesburg / This dissertation consists of a review of the literature, past and present, pertaining to the metal lithium. An overview is presented of its actions, its adverse effects, and its use in medicine particularly in psychiatry. As it is not irregular for many patients to receive two or more drugs concomitantly and often in a combination which has the potential to interact adversely, an overview of these interactions is also presented. / IT2018