京都大学 / 新制・課程博士 / 博士(医学) / 甲第23073号 / 医博第4700号 / 新制||医||1049(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 溝脇 尚志, 教授 黒田 知宏, 教授 増永 慎一郎 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

Background: Adolescence and young adulthood are particularly vulnerable periods for the development of mental health disorders, including bipolar disorder (BD). Mental health screening at universities could aid in the early identification of particularly at- risk individuals, with the long-term aim of providing early treatment interventions to improve clinical outcomes. However, further research into the identification of appropriate behavioral and biological markers for vulnerability to psychiatric disorders – as well as into the acceptability and efficacy of mental health screening - is warranted. Methods: Young adults were recruited via an already existing Internet-based mental health screening survey of undergraduate students at the University of Oxford. In Study 1, qualitative interviews of young adults with and without previous mental health problems were conducted to assess the acceptability and efficacy of mental health screening within a university setting. In Studies 2-5 we explored the hypotheses of altered emotional decision-making, reward processing and neurostructural integrity as behavioral and neurobiological markers for vulnerability to bipolar disorder via the study of young adults with a common bipolar phenotype (BPP) - some of whom meet diagnostic criteria for bipolar II or not-otherwise-specified disorder (BD II/NOS). To that end, we employed a diverse range of methodologies: alcohol challenge (Study 2); neuropsychological task performance (Study 3); functional magnetic resonance imaging (fMRI; Study 4); diffusion tensor imaging (DTI) and voxel-based morphometry (VBM; Study 5). Results: Findings from Study 1 suggest that young adults are willing to participate in mental health screening within a university setting, and that such screening may be used to offer subsequent treatment interventions. Taken together, findings from Studies 2 and 4 suggest a general blunted reward response among unmedicated young adults at increased risk for BD during euthymia, and additionally suggest pathophysiological similarities between BD and alcohol use disorders (AUDs) that may provide a causal link between the elevated co-occurrence rates of the two disorders. Finally, findings from Study 5 suggest widespread white matter microstructural alterations – which are likely to be neurodevelopmental in origin – among antipsychotic- and mood-stabilizer naïve young adults with BD II/NOS. Conclusions: These data support the hypothesis of neurodevelopmental alterations identifiable prior to significant clinical impairment among young adults at increased risk of – or already meeting DSM-IV criteria for – bipolar disorder. They also suggest that young adults in higher education are willing to participate in mental health screening. Future studies should aim to identify more specific markers for individual disorders such as BD.

<p>A more global analysis of the outcome of heart valve surgery is desirable to reflect the actual benefit for the patient. This thesis focuses on the preoperative assessment of the patient, and the outcome after surgery with regard to operative mortality, long-term survival, valve-related complications, and quality of life. </p><p>Magnetic resonance imaging and echocardiography were comparable in assessing severe mitral regurgitation, but did not agree in measuring regurgitant fraction. Natriuretic peptides correlated well to regurgitant fraction on magnetic resonance imaging and to PISA and vena contracta on echocardiography. </p><p>The risk of death, myocardial injury and postoperative heart failure after valve surgery has decreased over the last decade whereas the proportion older patients has increased. </p><p>Survival is reduced after mitral valve replacement in patients with severe symptoms whereas patients with less symptoms have excellent survival. Older patients are more often severly symptomatic at the time of mitral valve surgery. </p><p>Event-free survival is superior in patients with a mechanical prosthesis, but not influenced by valve type in older patients. A mechanical prosthesis is associated with a higher risk of bleeding < 5 years from surgery, especially in older patients; and a bioprosthesis is associated with a higher risk of thromboembolism > 5 years from surgery. Ageing with a mechanical prosthesis implied an increased risk for an adverse event, this was not true for bioprostheses. </p><p>Quality of life after complicated heart valve surgery resulted in reduced physical health but equal mental health compared to uncomplicated controls.</p>

A more global analysis of the outcome of heart valve surgery is desirable to reflect the actual benefit for the patient. This thesis focuses on the preoperative assessment of the patient, and the outcome after surgery with regard to operative mortality, long-term survival, valve-related complications, and quality of life. Magnetic resonance imaging and echocardiography were comparable in assessing severe mitral regurgitation, but did not agree in measuring regurgitant fraction. Natriuretic peptides correlated well to regurgitant fraction on magnetic resonance imaging and to PISA and vena contracta on echocardiography. The risk of death, myocardial injury and postoperative heart failure after valve surgery has decreased over the last decade whereas the proportion older patients has increased. Survival is reduced after mitral valve replacement in patients with severe symptoms whereas patients with less symptoms have excellent survival. Older patients are more often severly symptomatic at the time of mitral valve surgery. Event-free survival is superior in patients with a mechanical prosthesis, but not influenced by valve type in older patients. A mechanical prosthesis is associated with a higher risk of bleeding &lt; 5 years from surgery, especially in older patients; and a bioprosthesis is associated with a higher risk of thromboembolism &gt; 5 years from surgery. Ageing with a mechanical prosthesis implied an increased risk for an adverse event, this was not true for bioprostheses. Quality of life after complicated heart valve surgery resulted in reduced physical health but equal mental health compared to uncomplicated controls.