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（适用提供）：与NIMH研究领域标准背后的基本原理（RDOC）一致，我们提出了一项新的和意外的科学倡议，以通过维度的观点来评估双相情感障碍，这是通过“积极光谱性状的相互作用”（PSTS）（PSTS）与创造力，温度，人格和认知相关的。亲戚 双极患者，这一观点得到了许多研究的支持，但是没有研究评估了双相情感障碍的遗传负荷的可能优势。彼此之间，一些研究人员提出了双相情感障碍的平衡选择模型，根据“倒置-u”形曲线，亚阈值特征赋予了自适应优势，但尚未评估这些理论。我们建议，出现有益突变的原因是增加人类发展的认知，创造性和社会性质，有时会导致极端疾病。最近的全基因组关联结果表明，常见变异解释了躁郁症中至少25％的遗传差异，其中68％与精神分裂症共享是精神病的一般风险。普通变异在风险中的这种重要作用表明，健康个体中的大多数易感性等位基因都存在，这引起了人们的吸引力，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特征，这些特征是通过正面或平衡选择来维持的。支持这一观点的是研究报告基因与躁郁症，精神病和健康个体的创造力相关的阳性选择的证据（例如，NRG1）。与健康个体相比，大多数针对躁郁症的维度表型的研究都集中在患者及其一级亲属的定义上。相反，我们旨在确定与躁郁症谱相关的积极行为特征，可用于进一步阐明其潜在的遗传结构和进化环境。为了实现这一目标，我们将首先研究双极患者中选定的单个PST，临床上不受影响 兄弟姐妹和健康对照，随后验证了复合PST表型，这些表型可用于较大样品的未来遗传研究。我们的方法旨在评估普通人群中PST的连续体，其中双相情感障碍位于极端。此外，当前的精神病学实践更旨在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。创造性表达是一种幸福感的来源，双极患者经常由于创造力减少的主题经历以及其他不愉快的副作用而停止使用药物。因此，研究创造力与躁郁症之间的联系将促进对患者需求和经验的更深入了解，并促进更好的治疗和依从性。我们认为，我们的发现将是从病因和人口的角度以及促进更好的患者护理方面促进对躁郁症的理解的迈出的一步。