Neural processing of dyspnea in relation to the SLC6A4-genotype and different emotional contexts

慢性阻塞性肺疾病（COPD）是一种常见的严重呼吸道疾病，与焦虑和抑郁并存的高情绪负担有关。呼吸困难（呼吸困难）是高度厌恶和限制的主要症状。负面情绪通常与呼吸困难感知增加相关，然而，COPD患者的相应发现仍然有限，特定呼吸困难相关焦虑的特定影响广泛未知。此外，呼吸困难的神经处理也没有得到很好的理解，特别是检查负面情绪的相应影响的成像研究以及COPD患者的研究缺失。此外，基因变异对呼吸困难的感知和神经处理的影响尚不清楚，因此，计划中的研究项目将探讨呼吸困难的感知和神经处理与消极情绪、特定的呼吸困难相关焦虑以及与消极情绪相关的5-羟色胺转运体基因SLC 6A 4变异的关系。在三项使用磁共振成像（MRI）的相互关联的研究中，将在健康个体和COPD患者的遗传分层样本中分析功能激活模式以及结构细节。呼吸困难将由MRI扫描仪中的阻力负荷呼吸引起，并且部分地通过实验操作与局部脑血流进行情绪调节，从而允许对激活的脑区域进行推断。我们预计负面情绪以及呼吸困难相关的焦虑与情绪相关边缘系统的大脑激活之间存在关联，这在5-羟色胺转运体基因的风险等位基因携带者中尤为突出。此外，活动回避和功能能力下降的相关性将被测试。这一跨学科项目的结果将创建迫切需要的呼吸困难的感知和神经处理的基础知识，因此，可能有助于减轻COPD患者的疾病负担。

Chronic obstructive pulmonary disease (COPD) is a prevalent and severe airway disease and associated with high emotional burden due to co morbid anxiety and depression. Dyspnea (breathlessness) is the highly aversive and limiting cardinal symptom. Negative emotionality is often related to increased perception of dyspnea, however, respective findings in patients with COPD are still limited and the particular influence of specific dyspnea-related anxiety is widely unknown. Also the neural processing of dyspnea is not well understood, especially imaging studies examining the respective impact of negative emotionality as well as studies in patients with COPD are missing. Moreover, the influence of genetic variations on perception and neural processing of dyspnea is unknown.Therefore, the planned research project will examine the perception and neural processing of dyspnea in relation to negative emotionality, specific dyspnea-related anxiety and variations in the serotonin transporter gene SLC6A4, which is related to negative emotionality. In three interconnected studies using magnetic resonance imaging (MRI) functional activation patterns as well as structural specifics will be analyzed in genetically stratified samples of healthy individuals and patients with COPD. Dyspnea will be induced by resistive load breathing in the MRI-scanner and partly be emotionally modulated by experimental manipulations with regional cerebral blood flow allowing inferences on activated brain areas. We expect associations between negative emotionality as well as dyspnea-related anxiety and brain activations in the emotion-related limbic system, which are particularly prominent in risk-allele carriers of the serotonin transporter gene. Moreover, respective associations with activity avoidance and reduced functional capacity will be tested.Results of this interdisciplinary project will create urgently needed basic knowledge on perception and neural processing of dyspnea and, thus, might potentially contribute to reductions in the burden of disease in patients with COPD.