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

慢性阻塞性肺疾病(COPD)是一种常见且严重的呼吸道疾病，与焦虑和抑郁共同引起的高情绪负担有关。呼吸困难(呼吸困难)是高度厌恶和限制性的主要症状。负面情绪通常与呼吸困难的感觉增加有关，然而，在COPD患者中各自的研究结果仍然有限，特定的呼吸困难相关焦虑的特殊影响广泛未知。此外，对呼吸困难的神经处理也没有很好的了解，特别是检查负面情绪性的各自影响的成像研究以及对COPD患者的研究缺失。此外，遗传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检查呼吸困难的感知和神经处理与负面情绪、特定的呼吸困难相关焦虑以及与负面情绪相关的5-羟色胺转运体基因SLC6A4的变异。在使用磁共振成像(MRI)的三项相互关联的研究中，将分析健康人和COPD患者的基因分层样本中的功能激活模式以及结构细节。呼吸困难将由核磁共振扫描仪中的阻性负荷呼吸引起，并通过局部脑血流的实验操作部分调节情绪，从而对激活的大脑区域进行推断。我们预计，负面情绪性以及呼吸困难相关的焦虑和情绪相关边缘系统中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，还将分别测试与活动回避和功能能力降低的相关性。这一跨学科项目的结果将创建迫切需要的关于呼吸困难的感知和神经处理的基本知识，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.