Assessment of Positive Traits within the Bipolar Spectrum

 描述(由申请人提供)：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、未被探索的科学倡议，通过与创造力、气质、个性和认知灵活性相关的正频谱特征(PST)的相互作用，从维度的角度评估双相情感障碍。长期以来，人们注意到，积极特征或能力增强发生在未受影响的亲属中 双相患者，这一观点得到了许多研究的支持，但还没有研究评估基因负载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，亚阈值特征赋予适应优势，但这些理论尚未得到评估。我们认为，作为有益的突变而出现的增加发育中的人类的认知、创造性和社会性的突变最终导致了极端的疾病。最近的全基因组关联结果表明，共同变异至少解释了双相情感障碍25%的遗传变异，其中68%与精神分裂症共享，作为精神病的一般风险。共同风险变异的这种显著作用表明，大多数易感等位基因存在于健康个体中，这引发了一个有趣的问题，即在群体中传播的实际表型可能是调节健康个体行为的积极特征，这些特征是通过积极或平衡选择保持的。支持这一观点的研究报告了与双相情感障碍、精神病和创造力(例如，NRG1)相关的基因正向选择的证据。大多数关于双相情感障碍的维度表型的研究都集中在患者及其一级亲属与健康人相比的缺陷上。相反，我们的目标是识别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解释其潜在的遗传结构和进化背景。为了实现这一目标，我们将首先研究临床上未受影响的双相情感障碍患者中选定的个体PST。 兄弟姐妹和健康对照，随后验证复合PST表型，这些表型可用于未来更大样本的遗传学研究。我们的方法是根据双相情感障碍在普通人群中的连续体来评估维度。此外，目前精神病学的实践更多地着眼于控制双相情感障碍的症状，而不是了解患者的真正需求和潜在能力。创造性表达是幸福的一个来源，躁郁症患者经常因为主观经验创造力减弱以及其他令人不快的副作用而停止药物治疗。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验的更深入了解，并促进更好的治疗和依从性。我们相信，我们的发现将促进我们从病因学和人群角度对双相情感障碍的理解，并朝着促进更好的患者护理迈出一步。

 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.