Assessment of Positive Traits within the Bipolar Spectrum

双极谱中积极特质的评估

• 批准号: 8872348
• 负责人: TIFFANY A GREENWOOD
• 金额: $ 19.38万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-07 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8872348
• 关键词: Adverse effects; Affective; Age; Architecture; Behavior; Behavioral; Biology; Bipolar Disorder; Categories; Characteristics; Clinical; Clinical Distribution; Cognition; Cognitive; Complex; Creativeness; DNA; Diagnosis; Diagnostic; Discipline; Discrimination; Disease; Disease remission; Dose; Education; Ensure; Equilibrium; Ethnic Origin; Evolution; Family; First Degree Relative; Functional disorder; Funding; Future; General Population; Genes; Genetic; Genetic Load; Genetic study; Goals; Heritability; Human; Human Characteristics; Impairment; Individual; Knowledge; Lead; Link; Maintenance; Major Depressive Disorder; Manic; Measures; Methods; Modeling; Mood Disorders; Mutation; NRG1 gene; National Institute of Mental Health; Nature; Occupational; One-Step dentin bonding system; Patient Care; Patients; Personal Satisfaction; Personality; Pharmaceutical Preparations; Phenotype; Population; Prevalence; Psychiatry; Psychotic Disorders; Race; Relative (related person); Reporting; Research Domain Criteria; Research Personnel; Risk; Role; Sampling; Schizophrenia; Shapes; Siblings; Source; Susceptibility Gene; Symptoms; System; Temperament; United States National Institutes of Health; Validation; Variant; base; bipolar patients; bipolar spectrum; clinical care; clinical phenotype; compliance behavior; cost; data reduction; demographics; design; disorder risk; experience; fitness; flexibility; genetic variant; genome wide association study; improved; individualized medicine; new therapeutic target; public health relevance; risk variant; severe mental illness; social; theories; trait; transmission process

 DESCRIPTION (provided by applicant): Consistent with the rationale behind the NIMH Research Domain Criteria (RDoC), we propose a new and unexplored scientific initiative to evaluate bipolar disorder from a dimensional point of view via the interaction of `positive spectrum traits' (PSTs) related to creativity, temperament, personality, and cognitive flexibility.It has long been noted that positive traits or enhanced abilities occur in the unaffected relatives of bipolar patients, a view supported by numerous studies, yet no study has assessed a possible advantage of genetic loading for bipolar disorder. Accordingly, several investigators have suggested the balancing selection model for bipolar disorder, with adaptive advantages conferred by sub-threshold traits according to an `inverted-U' shaped curve, yet these theories have not been evaluated. We propose that what arose as beneficial mutations to increase the cognitive, creative, and social nature of developing humans eventually led to illness at the extreme. Recent genome-wide association results have suggested that common variation explains at least 25% of the genetic variance in bipolar disorder, 68% of which is shared with schizophrenia as a general risk for psychosis. This significant role of common variation in risk suggests that most susceptibility alleles exist in healthy individuals, raising the intriguing notin that the actual phenotypes being transmitted in the population may be positive traits that modulate behavior in healthy individuals, which are maintained through positive or balancing selection. Supporting this view are studies reporting evidence of positive selection for genes association with bipolar disorder, psychosis, and creativity in healthy individuals (e.g., NRG1). Most studies of dimensional phenotypes for bipolar disorder have focused on deficits in patients and their first-degree relatives compared with healthy individuals. Conversely, we aim to identify positive behavioral traits associated with the bipolar disorder spectrum that can be used to further explicate its underlying genetic architecture and evolutionary context. To achieve this goal, we will first investigate selected individual PSTs in bipolar patients, clinically unaffected siblings, and healthy controls with subsequent validation of composite PST phenotypes that can be used in future genetic studies of larger samples. Our approach is designed to evaluate dimensionality in terms of a continuum of PSTs in the general population, wherein bipolar disorder resides at the extreme. Furthermore, current practice in psychiatry is geared more towards controlling the symptoms of bipolar disorder, rather than understanding a patient's true needs and potential capabilities. Creative expression is a source of well-being, and bipolar patients often discontinue their medications due to subjective experiences of diminished creativity, among other unpleasant side effects. Studying the link between creativity and bipolar disorder will thus promote a deeper understanding of patients' needs and experiences and facilitate better treatment and compliance. We believe our findings will be one step toward advancing our understanding of bipolar disorder, from both etiological and population perspectives, and toward promoting better patient care.

 描述（申请人提供）：与NIMH研究领域标准（RDoC）背后的基本原理一致，我们提出了一个新的和未经探索的科学倡议，通过与创造力，气质，人格，长期以来，人们一直注意到，积极的特征或增强的能力发生在未受影响的亲属中， 这一观点得到了许多研究的支持，但还没有研究评估遗传负荷对双相情感障碍的可能优势。因此，一些研究人员提出了双相情感障碍的平衡选择模型，根据“倒U”形曲线，阈值下性状赋予适应性优势，但这些理论尚未得到评估。我们认为，那些作为有益突变而出现的、旨在增强人类认知、创造和社会性的基因，最终导致了极端的疾病。最近的全基因组关联结果表明，共同变异解释了双相情感障碍中至少25%的遗传变异，其中68%与精神分裂症共同作为精神病的一般风险。这种常见变异在风险中的重要作用表明，大多数易感等位基因存在于健康个体中，提出了一个有趣的观点，即在人群中传播的实际表型可能是调节健康个体行为的积极性状，通过积极或平衡选择来维持。支持这一观点的是一些研究，这些研究报告了健康个体中与双相情感障碍、精神病和创造力相关的基因的正选择证据（例如，NRG 1）。大多数关于双相情感障碍维度表型的研究都集中在患者及其一级亲属与健康个体相比的缺陷上。相反，我们的目标是确定与双相情感障碍谱相关的积极行为特征，这些特征可用于进一步阐明其潜在的遗传结构和进化背景。为了实现这一目标，我们将首先在双相情感障碍患者中研究选定的个体PST， 兄弟姐妹和健康对照，随后验证复合PST表型，可用于未来更大样本的遗传研究。我们的方法旨在评估维度方面的一个连续的PST在一般人群中，其中双相情感障碍居住在极端。此外，目前精神病学的实践更倾向于控制双相情感障碍的症状，而不是了解患者的真实需求和潜在能力。创造性的表达是幸福的源泉，双相情感障碍患者经常会因为创造力下降的主观体验而停止药物治疗，以及其他令人不快的副作用。因此，研究创造力和双相情感障碍之间的联系将促进对患者需求和经历的更深入理解，并促进更好的治疗和依从性。我们相信，我们的发现将是一个步骤，推进我们的理解双相情感障碍，从病因和人口的角度来看，并促进更好的病人护理。