Abstract：
Mixed features presentation in bipolar disorder (BD) represents the most severe form of the disease. BD may lead to cognitive and functional deterioration, a process known as neuroprogression, which appears to be exacerbated by increased serum levels of CCL11, a neuroprogression-related cytokine. Metabolic syndrome (MetS) is highly prevalent in BD, and it is known that the presence of MetS may increase inflammation, which may contribute to increased CCL11 levels, and consequently impact on the severity of the disorder. What is not known is whether the MetS mediates the association between CCL11 levels and the presence of mood episodes with mixed features in BD. Therefore, the aim of this study was to investigate the mediating effect of MetS on the relationship between CCL11 levels and the presence of mood episodes with mixed features in BD, in a population-based study. This is a cross-sectional study that included 184 young adults, 92 with BD and 92 populational controls, matched by sex and age. BD diagnosis was assessed using the Mini International Neuropsychiatric Interview - PLUS. Mood episodes with mixed features was defined according to DSM-IV and DSM-5 criteria. MetS was defined according to the National Cholesterol Education Program (NCEP/ATP III). Substance use was assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). CCL11 serum levels were analyzed using the multiplex analysis method Luminex 200™ system. The mediation model was tested using the MedMod module of the JAMOVI 2.4.8 software. Mediation analysis indicated a trend towards significance of MetS mediating the association between CCL11 and the presence of a mood episode with mixed features in BD (p = 0.065). Individuals with BD presenting with a mood episode with mixed features and MetS may have accelerated neuroprogression due to the influence of MetS on CCL11 levels, therefore, assessing for MetS occurrence in this population and implementing early interventions to prevent its development may be effective ways of delaying cognitive impairments related to this cytokine.
摘要：
双相情感障碍（BD）中出现的混合特征代表了该疾病的最严重形式。BD可能导致认知和功能恶化，一个被称为神经进展的过程，CCL11（一种神经进展相关的细胞因子）的血清水平升高似乎加剧了这种情况。代谢综合征（MetS）在BD中非常普遍，众所周知，MetS的存在可能会增加炎症，这可能有助于增加CCL11水平，从而影响疾病的严重程度。未知的是MetS是否介导CCL11水平与BD中具有混合特征的情绪发作之间的关联。因此,这项研究的目的是调查MetS对CCL11水平与BD中混合特征的情绪发作之间的关系的中介作用。在一项基于人群的研究中。这是一项横断面研究，包括184名年轻人，92个BD和92个人口控制，性别和年龄相匹配。使用Mini国际神经精神病学访谈-PLUS评估BD诊断。根据DSM-IV和DSM-5标准定义具有混合特征的情绪发作。根据国家胆固醇教育计划（NCEP/ATPIII）定义MetS。通过酒精评估物质的使用，吸烟和物质参与筛查测试（ASSIST）。使用多重分析方法Luminex200™系统分析CCL11血清水平。使用JAMOVI2.4.8软件的MedMod模块测试调解模型。中介分析表明，MetS介导CCL11与BD中具有混合特征的情绪发作之间存在关联的重要性趋势（p=0.065）。由于MetS对CCL11水平的影响，BD表现出混合特征和MetS的情绪发作的个体可能会加速神经进展。因此,评估该人群中MetS的发生并实施早期干预措施以预防其发展可能是延缓与该细胞因子相关的认知障碍的有效方法。
