Dynamic Inflammatory and Mood Predictors of Cognitive Aging in Bipolar Disorder

随着人口老龄化，对个人和社会造成的认知负担和健康影响严重 精神疾病，如双相情感障碍（BD），将增加。过早和加速老化轨迹 BD开始在许多健康和认知领域得到认可，但具体机制还没有 尤其是在认知老化的过程中。炎症功能的标志物，如 已知细胞因子水平会影响认知，随年龄变化，并预测心理健康状况的下降。 个体BD患者的细胞因子水平也出现异常，但BD患者的情绪不稳定使得 炎症和认知测量的短期和长期变化的测量具有挑战性。 尽管如此，在这一人群中进行的研究提供了一个独特的机会，可以更好地了解 情绪和行为失调的程度可以调节或介导免疫认知 协会.我们建议使用创新的多队列爆发纵向设计（MBLD）来表征 认知和炎症反应的轨迹，并确定：1）认知和 炎症在短期内，同时考虑情绪变化的影响，2）基线测量和水平 炎症标志物的短期变异性可能预测认知变化的长期轨迹， 和3）长期的炎症、认知和情绪变量之间的关系（即，机制 改变）。我们将评估144名患有临床相关情绪失调症状的成年人（35-60岁）， 如双极I诊断所示，115名年龄相似的非BD比较（NC）参与者， 精神疾病认知、细胞因子水平和情绪（沿着其他潜在的影响变量）将被 使用密集的远程监测和家访（突发），在两周内每周或每天测量一次 评估）。BD将每年重复一次爆破评估（纵向评估），持续3年 NC组术后1年。该项目涉及NIMH战略目标#2：绘制心理图表 疾病轨迹，以确定何时，何地以及如何干预。具体来说，使用创新的设计 这让我们能够解释和衡量情绪症状的变化，我们可以发现， 预测个体认知变化过程的炎症标志物（静态和动态） 情绪不稳定通过了解炎症、认知、 情绪，药物和行为干预可以被设计来减缓或逆转 双相情感障碍的功能下降。

As the population ages, the burden on individuals and society due to the cognitive and health effects of serious mental illnesses, such as bipolar disorder (BD), will increase. Premature and accelerated aging trajectories in BD are beginning to be recognized in many health and cognitive domains, but specific mechanisms have not yet been identified, particularly for the course of cognitive aging. Markers of inflammatory function, such as cytokine levels, are known to affect cognition, change with age, and predict declines in mentally healthy individuals. Cytokine levels also appear to be abnormal in those with BD, but mood instability in BD makes measurement of short- and long-term changes in both inflammatory and cognitive measures challenging. Nonetheless, studies within this population afford a unique opportunity to better understand how variations in the degree of emotional and behavioral dysregulation may moderate or mediate immune-cognitive associations. We propose to use an innovative multi-cohort burst longitudinal design (MBLD) to characterize trajectories of cognitive and inflammatory response and identify: 1) relationships between cognition and inflammation in the short term while accounting for effects of mood variability, 2) baseline measures and levels of short-term variability in inflammatory markers that might predict long-term trajectories of cognitive change, and 3) relationships between inflammatory, cognitive, and mood variables in the long-term (i.e., mechanisms of change). We will assess 144 adults (35-60 years old) with clinically-relevant symptoms of mood dysregulation, as indicated by Bipolar I diagnosis, and 115 similarly aged non-BD comparison (NC) participants without mental illnesses. Cognition, cytokine levels, and mood (along with other potential contributing variables) will be measured weekly or daily over a two week period using intensive remote monitoring and home visits (burst assessment). Burst assessments will be repeated annually (longitudinal assessment) for three years in the BD group, and at one year in the NC group. This project addresses NIMH Strategic Objective # 2: charting mental illness trajectories to determine when, where, and how to intervene. Specifically, using an innovative design that allows us to account for, and measure the impact of, variability in mood symptoms, we can discover inflammatory markers (both static and dynamic) that predict the course of cognitive change among individuals with mood instability. By understanding the complex and dynamic interplay between inflammation, cognition, and mood, pharmacologic and behavioral interventions can be designed to slow or reverse the trajectory of declining function in bipolar disorder.