Longitudinal Assessment of Manic Symptoms (LAMS) Study

描述（由申请人提供）：本竞争性延续申请要求提供资金以继续在 4 个地点进行躁狂症状纵向评估 (LAMS) 研究。在过去的 3.5 年里，使用有效且可靠的筛查工具，6-12 岁的儿童在首次临床表现时就被诊断出患有躁狂症状 (ESM) 升高。大约 621 名青少年被确定患有 ESM。此外，还纳入了 86 名首次临床表现时未出现 ESM 的年龄/种族/性别匹配的对照儿童。在 LAMS 研究期间，这些参与者在基线时以及此后每 6 个月接受一次评估。在每个评估点，对青少年的精神病诊断、精神病症状、心理健康服务利用和心理社会功能进行评估。作为该竞争性延续申请 (LAMS2) 的一部分，研究人员建议继续进行为期 6 个月的评估。此外，LAMS2 将包括神经认知测试和神经影像技术，以便识别可能的生物标志物，这些生物标志物反映或与使个体容易患双相情感障碍的潜在生物机制相关。 根据 NIMH 的战略计划，LAMS2 将重点检查和记录患有 ESM 和相关精神疾病的青少年的轨迹，以便更好地确定干预的关键时间点。更具体地说，LAMS2 的目标包括： 1) 检查 ESM 随着时间的推移与情绪症状变化和情绪障碍 DSM-IV-TR 标准的稳定性； 2) 单独检查 ESM 以及与其他潜在危险因素相结合的阳性预测价值，以便更好地识别在进入青春期并度过青春期时最终会患上双相情感障碍 (BPD) 的青少年； 3) 制定双相谱系障碍儿科表型的基于证据的理论诊断标准； 4) 确定与 ESM 青少年功能不良相关的风险因素； 5）随着时间的推移，检查情绪发作与临床结果之间的关系； 6) 评估神经认知表现，以及选定神经系统的功能异常及其与 ESM 的关系以及青少年和成年早期 BPD 的发展。目前的参赛者将开始竞争性更新期，年龄范围为8-17岁。到 2015 年 6 月 LAMS2 结束时，队列的年龄范围为 13 至 22 岁。因此，LAMS 2 将提供一个机会，在研究参与者进入双相谱系障碍高风险年龄的一段时间内收集创新和临床重要数据。 公共卫生相关性：诊断青少年双相情感障碍 (BPD) 存在很大争议。 LAMS2 的目标是： 1) 提高诊断的清晰度（即根据经验区分谁符合诊断标准，谁不符合诊断标准；为青少年制定基于证据的诊断标准指南）； 2) 提高对促使高危青少年陷入或远离边缘性人格障碍的风险和保护因素的了解； 3) 提高对改善或损害这些青少年功能结果的风险和保护因素的认识； 4) 了解随着时间的推移，是否患上 BPD 的青少年所发生的大脑结构和功能异常。

DESCRIPTION (provided by applicant): This competing continuation application requests funds to continue the Longitudinal Assessment of Manic Symptoms (LAMS) study at 4-sites. Over the past 3.5 years, using a valid and reliable screening instrument, children ages 6-12 years were identified with elevated symptoms of mania (ESM) at the time of their first clinical presentation. Approximately 621 youth were identified as having ESM. In addtion, 86 age/race/sex matched comparison children without ESM at first clinical presentation were enrolled. During the LAMS study, these participants were evaluated at baseline and every 6 months thereafter. At each assessment point, youths were evaluated regarding their psychiatric diagnoses, psychiatric symptomatology, mental health service utilization, and psychosocial functioning. As part of this competing continuation application (LAMS2), the investigators propose to continue these 6-month evaluations. In addition, LAMS2 will include both neurocognitive testing as well as neuroimaging techniques in order to identify possible biomarkers that reflect or are related to underlying biological mechanisms that predisopose individuals to the development of bipolar disorders. In acordance with the NIMH's Strategic Plan, LAMS2 would focus on examining and documenting trajectories of youths with ESM and related psychiatric disorders in order to better identify crucial timepoints for intervention. More specifically, the goals of LAMS2 include: 1) examining the stability of ESM over time in relation to changes in mood symptoms and DSM-IV-TR criteria for mood disorders; 2) examining the positive predictive value of ESM alone and in combination with other potential risk factors in order to better identify youth who will eventually develop bipolar disorders (BPD) as they progress into and through adolescence; 3) developing evidence-based, atheoretical, diagnostic criteria for a pediatric phenotype for bipolar spectrum disorders; 4) identifying risk factors associated with poor functional outcomes for youth with ESM; 5) examining the relationships between mood episodes and clinical outcomes over time; 6) evaluating neurocognitive performance, together with functional abnormalities in selected neural systems and their relationship to ESM and the development of BPD during youth and early adulthood. The current participants will begin the competitive renewal period ranging in age from 8-17 years. At the end of LAMS2, June 2015, the cohort will range in years from 13-22 years. For this reason, LAMS 2 will provide an opportunity for the collection of innovative and clinically important data during a period of time in which when study participants will have entered an age of high risk for the development of a bipolar spectrum disorder. PUBLIC HEALTH RELEVANCE: Diagnosing bipolar disorders (BPD) in youth is highly controversial. Goals of LAMS2 are to: 1) increase clarity of diagnosis (i.e., empirically delineate who does versus does not meet diagnostic criteria; develop evidence-based guidelines for diagnostic criteria in youth); 2) improve understanding of risk and protective factors that propel high-risk youth into, or away from developing BPD; 3) increase awareness of risk and protective factors that improve or detract from functional outcome for these youth; 4) learn about the structural and functional brain abnormalities that occur in youth who do, versus do not, develop BPD over time.