哮喘与情绪相关性的理论及临床研究
摘要
目的：
哮喘,古代中医将之分为哮和喘两类。哮证,是发作性痰鸣气急的疾患,简称哮,古代称之为“哮吼”、“呷嗽”等,该名称首见《医学正传·哮喘》。喘证是指由于外感或内伤,导致肺失宣降,肺气上逆或气无所主,肾失摄纳,以致呼吸困难,甚则张口抬肩,鼻翼煽动,不能平卧等为主要临床特征的一种病证,严重者可由喘致脱出现喘脱之危重证候。喘证在古代文献中又称为“鼻息”、“肩息”、“上气”、“逆气”、“喘促”等。现代中医一般把哮和喘并称为哮喘。
“神”在中医理论中有广义和狭义两种含义,广义的神是指人的生命活动外在总的表现,而狭义的神则指人的精神情志、思维活动。中医四大经典著作之首《黄帝内经》很早就指出,“神”的失常是所有疾病发病的基础,人的七情(喜、怒、忧、思、悲、恐、惊)失常会引发多种疾病,恐惧、抑郁、悲伤等不良情绪更是引发哮喘的主要原因之一,很多古代医书都对此有过描述,如《医学入门·喘》说：“惊忧气郁,惕惕闷闷,引息鼻张气喘,呼吸急促而无痰声者”,清晰地说明了各种不良情绪与哮喘发病之间的关系。
虽然自古中医就认识到哮喘与不良情绪之间关系密切,但在当今哮喘病的临床治疗中,无论在中国还是美国,患者的情绪状态却未被给予足够的重视,这种状况可能是由于临床工作中的诸多因素引起的,如医生的时间有限故无法与患者详细交流、患者因诸多原因不能向医生敞开心扉、或不能向医生描述自己情绪的详细状况,还有很多因素很容易被掩盖,故只能仅举几例。这种状况造成哮喘病患者在治疗和康复过程中,疗效可能受到一定影响。
基于上述原因,为强调情绪因素在哮喘发病中的致病作用及在今后中西医临床治疗哮喘的过程中更加重视对患者情绪状态的调节和干预,本课题选择中医七情中的悲伤、恐惧、愉悦等情绪,初步从理论和临床角度对其与哮喘之间的相关性展开探讨和研究。
本课题力图从中医理论分析和临床研究角度对情绪(如悲伤、恐惧、愉悦)如何影响哮喘病的发病、症状、预后等进行深入探讨,并结合其他多个学科的研究如肺内科、神经内分泌学、免疫学、分子心理学、系统生物学等以及笔者在临床试验中收集到的数据,初步分析哮喘与情绪(悲伤、恐惧、愉悦)之间相关性的内在机制,重点探讨悲伤和恐惧等不良情绪在肺功能和哮喘控制方面的对神经呼吸功能的特异性影响,阐明一个更全面的用于解释不良情绪在疾病(哮喘)中所扮演角色的科学模型,从现代医学角度演绎中医经典著作《黄帝内经》中所探讨的情志因素与疾病的相关性的观点,为中医理论提供更多的西方科学基础,并希冀在未来可以帮助中西医对具体情绪在不同类型疾病的发病中所扮演的角色及其机理作更深入研究,并在治疗疾病中更多关注对“神”的调节,这也正是中医一直所强调的治疗疾病的重要基础。
方法：
一.文献研究
通过查阅文献,汇总中医及西医肺内科、免疫学、神经内分泌学、分子心理学、系统生物学等学科方面的相关文章,提取有效部分,重点分析和探讨与以下问题有关的部分：《黄帝内经》及后世中医是怎样探讨哮喘与情绪的,哮喘和不良情绪之间存在什么关系；西医过去和现在有关哮喘研究的趋势是什么；哮喘和情绪失常相关的真实性体现在哪些方面；哮喘与情绪之间相关的机制是什么；系统生物学是怎样认识哮喘的等。
通过文献分析和讨论,全面归纳总结情绪的神经调控功能对哮喘呼吸状态的影响,据此,一个更全面的建立在《黄帝内经》及中医理论基础上的西方科学哮喘模型得到修订。
二.临床研究
自2011年9月-12月南海中医院哮喘中心收集38例哮喘患者,随机分为2组,分别给患者观看时长约8分钟的电影片段(分2类：第一组患者：观看令人愉悦的电影片段；第二组患者：观看令人悲伤/恐惧的电影片段,各组患者均观看同一电影片段)；情绪刺激建立在情感同质图片系列研究标准(IAPS)的基础上；呼吸量检测仪检测患者的FEV1(第一秒最大呼气量)和FEV1%(FEV1占预计值百分比)、呼吸频率、脉率、脉象、收集患者的个人史资料,经筛选35例患者进入初选(3名患者检测结果无效)。一个月后,收集所有患者的ACT(哮喘控制)得分,4名患者失去联系,最终31名患者进入本研究,第一组17人(Groupl,17patients),第二组14人(Group2,14patients)。
1.哮喘程度
按照临床标准,选择中度到重度的哮喘患者进入本研究,包括偶发哮喘、频发哮喘、持续性哮喘。
1.1偶发哮喘：指哮喘发作频率低于每3-4周一次,伴病毒性上呼吸道感染。此类患者在哮喘每次发作之间完全无症状,无需每天服用抗哮喘药物,通常需吸入β2剂。
1.2频发哮喘：指哮喘发作频率至少为每2-3周一次,哮喘每次发作之间无症状。此类患者通常需吸入色甘酸钠)或皮质激素以控制症状。由于无副作用,色甘酸钠为轻中度哮喘患者的首选药物。
1.3持续性哮喘：指大部分时候都有哮喘症状.此类患者通常需定时吸入皮质类固醇以控制症状,也需要长期服用支气管扩张药(施立稳/沙美特罗)。此类患者通常不需要每天服用皮质类固醇或氨茶碱。
2.纳入标准年龄：18-65岁；不吸烟者。
3.哮喘诊断
哮喘但不伴见其他严重复杂的因素如影响多系统功能的慢性疾病。
经肺功能检查诊断,患者有轻度至重度哮喘,在吸入支气管刺激剂后肺功能至少减少20%,并伴见气道其他症状如胸部不适、咳嗽、半夜咳嗽等。
4.排除标准
排除慢性重病如充血性心衰、肿瘤等,以及其他情况如怀孕。
5.测定血皮质醇(COR)
6.检测FF.V1
指一秒用力呼气容积：吸气至肺总量位后一秒之内快速呼出气量。
7.检测用力肺活量Forced vital capacity(FVC)
也称时间肺活量,是指将测定肺活量的气体用最快速呼出的能力,以升为单位测量,通常是检测呼吸量时的最基本方法。
8.FEV1/FVC (FEV1％)
健康成年人的FEV1%通常约为75-80%,在阻塞性疾病(哮喘,慢性阻塞性肺病,慢性支气管炎,肺气肿)患者中,FEVl通常减少,FVC通常也会由于呼气时气道过早关闭而降低,只是和FEV1降低的程度不同,例如,FEV1和FVC都降低,但FEV1由于增加的气道阻力而降低的更多,因为增加的气道阻力会影响呼出气流,这样就会导致FEV1%减少至<80%,甚至经常<45%。
9.资料收集程序
第1步：收集患者姓名、年龄、就诊日期、哮喘等级、电话、医疗卡号,患者随机分至第1组(观看令人愉悦的电影片段)或第2组(观看令人恐惧／悲伤的电影片段)。
第2步：基础脉率、呼吸频率、中医脉象、ACT得分。
第3步：输入患者的年龄、身高、体重和性别,校准呼吸量检测仪。
第4步：指导患者在尽力吸气后首先用力呼气并持续呼尽,记录FEV1、FEV1%。
第5步：患者排除外界环境干预,集中精神观看会引起悲伤恐惧或愉悦心情的电影片段,时长约8分钟。
第6步：观看电影结束后,再次指导患者在尽力吸气后首先用力呼气并持续呼尽,记录FEV1和FEV1%。
第7步：测量情绪干预后的呼吸频率和脉率。
第8步：询问患者观看电影够的反应和内心感觉。
第9步：询问患者个人史,如何时诊断为哮喘,第一次发生哮喘的时间以及当时生活中是否发生对其情绪有影响的事件,幼年的性格状况以及患者对于自己目前情绪状态的描述。
第10步：一个月后,在自体血穴位注射治疗一个完整周期后收集患者的ACT。
10.环境控制
空调环境保持室内温度恒定适中,控制空气湿度至适中。诊室安静,与其他患者隔离,保证观看电影片段的有效性。室内光线恒定。
11.医生的关怀
对所有患者医生保持同样的关注和热情,允许患者提问,患者有疑问时需帮助解决,但不向患者透露有关本研究性质的任何引导性信息。
12.统计学处理
所有数据用x±s表示,组间比较采用t检验,STATA10.0软件进行数据分析,P<0.05表示有统计学差异,P<0.01表示有显著差异。
成果：
一.理论研究结果
中医研究结果显示,《黄帝内经》是最早记载哮喘与情绪之间有相关性的著作,自此以后,中医历代典籍中有大量文献记载相关内容,并在《黄帝内经》的基础上,不断深入探讨和分析二者之间的相关性,从中医角度探讨了二者相关性的机制,提示随着中医学的发展,对哮喘的病因病机、症状、预后的认识越来越丰富,甚至对后世方剂学的发展都产生了重大影响,明代《医便》记载的五磨饮子治疗肺气郁闭型的实喘就是一个典型例子,该方中的五味中药木香、乌角沉香、槟榔、枳实、台乌药均为开郁降气之药,足以说明当时的医生已经充分认识到哮喘与情绪之间的相关性。
西医文献研究结果显示,与恐惧和悲伤等情绪相关的大脑中枢与哮喘之间有相互联系,这为《黄帝内经》乃至整个中医理论研究的领域创立了新的思路。同时研究显示,今后哮喘研究的新趋势将会以建立在中医阴阳理论和整体观基础上的系统生物学知识为依据,进一步分析和解释哮喘与情绪之间相关性的机理。
二.临床研究结果
组1患者在观看令人心情愉悦的电影片段前后呼吸频率发生明显变化,即观看电影后呼吸频率显著减慢,有统计学差异(P<0.05),说明良好的心情会对哮喘患者的呼吸状态有正面影响,这与观看电影后对患者的心理状态的询问结果是一致的,大部分患者均表示看完电影片段后心情愉悦,呼吸频率的减慢提示气机和缓,呼吸深度的增加；组2患者在观看令人心情悲伤／恐惧的电影片段前后呼吸频率亦发生明显变化,即观看电影后呼吸频率显著加快,有显著统计学差异(P<0.01),说明不良的心情会对哮喘患者的呼吸状态有负面影响,这与观看电影后对患者的心理状态的询问结果是一致的,大部分患者均表示看完电影片段后心情紧张沉重或忧伤,呼吸频率的加快提示呼吸深度的降低。
两组患者之间观看电影前后心率比率(即PR2/PRl)和呼吸比率(RR2/RR1)之间的相互比较结果均有显著统计学差异(P<0.01,P<0.01),均进一步说明良好的情绪状态对缓解哮喘症状有重要作用,而不良的情绪状态则会加重哮喘患者的症状。
组1患者两次ACT得分比较有显著统计学差异(P<0.01),其中ACT1是在患者进入研究后即刻测试的结果,而ACT2是在ACT1得分测试结束后马上观看电影,进行良好的情绪干预后并接受自体血穴位注射完整一个周期后再次检测得出的结果,ACT2得分较ACT1得分明显上升,说明良好的情绪干预及结合自体血穴位注射治疗较大地改善了患者的哮喘病情。
两组患者之间两次FEV1比率(即1stFEV1/2ndFEV1之间相互比较有统计学差异(P<0.05),说明由不同类型的电影片段引起不同的情绪状态后对哮喘患者的肺功能有较大影响,说明良好的情绪状态对增强哮喘患者一秒用力呼气容积有重要作用,而不良的情绪状态则会使哮喘患者的一秒用力呼气容积降低。
其余的各项比较虽均无统计学差异,但大部分可观察到数据均有上升或下降的趋势,分析其原因,主要是因为哮喘患者临床症状和肺功能的改善,是需要一个较长的过程才能明显体现出来的,短时间的情绪干预不可能很大程度地改变患者的各项指标,但指标改变的趋势仍可观察到,说明良好或不良情绪干预,分别有正面和负面改变患者哮喘状态和肺功能的作用趋势。
结论：
《黄帝内经》是中医理论的基石,本研究把《黄帝内经》首先提出的悲恐等情绪与哮喘发病之间有密切联系的观点在现代科学中发现了依据,即与哮喘相关的人体大脑中枢亦与悲伤、恐惧等不良情绪相关。同时,这对系统生物学领域的研究也有好处,即为其提供了情绪与哮喘之间具有相关性的观点,并希望未来有更多的系统生物学家进一步研究内经,研究中医,挖掘中医理论的实质,赋予中医理论的内涵更多的意义,因系统生物学在研究中医及《黄帝内经》方面最具潜力。
情绪状态在一定程度上会影响哮喘患者的肺功能和改变患者的哮喘状态,即良好的情绪对哮喘患者有一定的正面作用,能减慢患者的心率、呼吸频率,对患者的ACT及FEV1也有一定的改善作用；而不良的情绪状态,即本研究所讨论的悲伤和恐惧心理,则对患者有一定的负面影响,能加快患者的心率、呼吸频率,降低患者的FEV1等。
研究提示,中医所说的“神”在哮喘病的发病过程中起重要作用,临床治疗哮喘若忽视对患者“神”即情绪的正面调节和干预,将会在一定程度上影响疗效,而重视对患者不良情绪心理状态的调节,将会对促进临床疗效的提高起到重要作用,我想这就是本研究的目标之所在。
Objective
Huang Di Nei Jing discusses the role of shen disturbance as the basis of all diseases and that the emotions of fear and sadness are most predominant in the disease of asthma. While Western medicine has confirmed that depression and anxiety are associated with onset and exacerbation of asthma most studies in emotional research focus on non-explicit emotions but only dysregulation of anxiety and depression. This study was designed with specificity of nueurorespiratory function of sadness and fear in lung function and asthma control. Thus, this study hopes to contribute more support from a Western scientific basis for Huang Di Nei Jing.
Methods
1.Theoretical research
Articles from multiple disciplines of science (such as pulmonary medicine, immunology, neuroendocrinology, molecular psychology, systems science, etc.) were collected and analyzed according to certain questions such as:what is the validity of emotional dysregulation and asthma correlation, what is the mechanism of emotions and asthma, what are past and current research trends in asthma, explain systems biology research into asthma, what does Huang Di Nei Jing original articles say about emotions and asthma etc. Information was extracted and synthesized into a robust review of current thinking on emotional neuroregulatory functions of respiration in asthma. From this, a more thorough Western scientific model for asthma in Huang Di Nei Jing could be devised.
2. Clinical Research
38asthma patients were collected at Guangdong NanHai TCM hospital and shown affective video clips (8minutes) of either a content neutral/pleasant (Group 1) or sad/fearful (Group2) emotional stimulation based on research standard of affectively homogeneous picture series (IAPS). FEV1and FEV1%, breath rate, pulse rate, pulse quality, and social history were collected. One month later, ACT scores were collected.35patients were collected initially but due to inability to contact after one month, the patients were reduced to31in the study. Environment controls such as temperature regulation, clearing humidity, separation from distraction and doctors attention were regulated.
Results
1. Theoretic research
Found that there is a correlation with asthma and brain centers that are associated with fear and sadness which was synthesized information from different studies combined together. Therefore, creating new knowledge in the realm of Huang Di Nei Jing research. As well, this research found that the direction of asthma study could trend in the direction of systems biology to further explain the emotions and asthma mechanism.
2. Clinical research
When comparing Group1with Group2in a ratio, the patients in Group1had statistically higher FEV1when compared to Group2(p<0.05). By the value of the ratio, we could see the direction/trend of the changing of the observation point/index. When looking at the change in FEV1Group1's FEV1rose while Group2decreased. However, while there was a trend in rising and falling, it did not prove to be statistically valid with a (p>0.05) when looking at the rise and fall alone.
Conclusion
1. Theoretic research
Huang Di Nei Jing is the foundation of all Chinese Medicine. This study found new knowledge in the area of brain regions correlating with asthma control correlating with sadness and fear as was first put forth by Huang Di Nei Jing. As well, this could be useful in the area of research in Systems biology showing a level of connectedness and hope to attract systems biologist to further investigating Huang Di Nei Jing. This study helps to show that systems biology may hold great potential in scientifically explaining Huang Di Nei Jing.
2. Clinical Research
While there were some problems with the research statically in the FEV1changes in Group1and2, this could probably have to do with the some difficulties in the clinical setting such as patients'inability to fully comply with breathing technique required for spirometry machinery, attention span or interest in films, or other unknowns not foreseen. However, despite this, there was an obvious trend in lowering lung function in sadness and fear related movies. As well, the data proved that there is a statistical difference between the change when comparing Group1and Group2in a ratio where Group1FEV was higher than Group2.
哮喘,古代中医将之分为哮和喘两类。哮证,是发作性痰鸣气急的疾患,简称哮,古代称之为“哮吼”、“呷嗽”等,该名称首见《医学正传·哮喘》。喘证是指由于外感或内伤,导致肺失宣降,肺气上逆或气无所主,肾失摄纳,以致呼吸困难,甚则张口抬肩,鼻翼煽动,不能平卧等为主要临床特征的一种病证,严重者可由喘致脱出现喘脱之危重证候。喘证在古代文献中又称为“鼻息”、“肩息”、“上气”、“逆气”、“喘促”等。现代中医一般把哮和喘并称为哮喘。
“神”在中医理论中有广义和狭义两种含义,广义的神是指人的生命活动外在总的表现,而狭义的神则指人的精神情志、思维活动。中医四大经典著作之首《黄帝内经》很早就指出,“神”的失常是所有疾病发病的基础,人的七情(喜、怒、忧、思、悲、恐、惊)失常会引发多种疾病,恐惧、抑郁、悲伤等不良情绪更是引发哮喘的主要原因之一,很多古代医书都对此有过描述,如《医学入门·喘》说：“惊忧气郁,惕惕闷闷,引息鼻张气喘,呼吸急促而无痰声者”,清晰地说明了各种不良情绪与哮喘发病之间的关系。
虽然自古中医就认识到哮喘与不良情绪之间关系密切,但在当今哮喘病的临床治疗中,无论在中国还是美国,患者的情绪状态却未被给予足够的重视,这种状况可能是由于临床工作中的诸多因素引起的,如医生的时间有限故无法与患者详细交流、患者因诸多原因不能向医生敞开心扉、或不能向医生描述自己情绪的详细状况,还有很多因素很容易被掩盖,故只能仅举几例。这种状况造成哮喘病患者在治疗和康复过程中,疗效可能受到一定影响。
基于上述原因,为强调情绪因素在哮喘发病中的致病作用及在今后中西医临床治疗哮喘的过程中更加重视对患者情绪状态的调节和干预,本课题选择中医七情中的悲伤、恐惧、愉悦等情绪,初步从理论和临床角度对其与哮喘之间的相关性展开探讨和研究。
本课题力图从中医理论分析和临床研究角度对情绪(如悲伤、恐惧、愉悦)如何影响哮喘病的发病、症状、预后等进行深入探讨,并结合其他多个学科的研究如肺内科、神经内分泌学、免疫学、分子心理学、系统生物学等以及笔者在临床试验中收集到的数据,初步分析哮喘与情绪(悲伤、恐惧、愉悦)之间相关性的内在机制,重点探讨悲伤和恐惧等不良情绪在肺功能和哮喘控制方面的对神经呼吸功能的特异性影响,阐明一个更全面的用于解释不良情绪在疾病(哮喘)中所扮演角色的科学模型,从现代医学角度演绎中医经典著作《黄帝内经》中所探讨的情志因素与疾病的相关性的观点,为中医理论提供更多的西方科学基础,并希冀在未来可以帮助中西医对具体情绪在不同类型疾病的发病中所扮演的角色及其机理作更深入研究,并在治疗疾病中更多关注对“神”的调节,这也正是中医一直所强调的治疗疾病的重要基础。
方法：
一.文献研究
通过查阅文献,汇总中医及西医肺内科、免疫学、神经内分泌学、分子心理学、系统生物学等学科方面的相关文章,提取有效部分,重点分析和探讨与以下问题有关的部分：《黄帝内经》及后世中医是怎样探讨哮喘与情绪的,哮喘和不良情绪之间存在什么关系；西医过去和现在有关哮喘研究的趋势是什么；哮喘和情绪失常相关的真实性体现在哪些方面；哮喘与情绪之间相关的机制是什么；系统生物学是怎样认识哮喘的等。
通过文献分析和讨论,全面归纳总结情绪的神经调控功能对哮喘呼吸状态的影响,据此,一个更全面的建立在《黄帝内经》及中医理论基础上的西方科学哮喘模型得到修订。
二.临床研究
自2011年9月-12月南海中医院哮喘中心收集38例哮喘患者,随机分为2组,分别给患者观看时长约8分钟的电影片段(分2类：第一组患者：观看令人愉悦的电影片段；第二组患者：观看令人悲伤/恐惧的电影片段,各组患者均观看同一电影片段)；情绪刺激建立在情感同质图片系列研究标准(IAPS)的基础上；呼吸量检测仪检测患者的FEV1(第一秒最大呼气量)和FEV1%(FEV1占预计值百分比)、呼吸频率、脉率、脉象、收集患者的个人史资料,经筛选35例患者进入初选(3名患者检测结果无效)。一个月后,收集所有患者的ACT(哮喘控制)得分,4名患者失去联系,最终31名患者进入本研究,第一组17人(Groupl,17patients),第二组14人(Group2,14patients)。
1.哮喘程度
按照临床标准,选择中度到重度的哮喘患者进入本研究,包括偶发哮喘、频发哮喘、持续性哮喘。
1.1偶发哮喘：指哮喘发作频率低于每3-4周一次,伴病毒性上呼吸道感染。此类患者在哮喘每次发作之间完全无症状,无需每天服用抗哮喘药物,通常需吸入β2剂。
1.2频发哮喘：指哮喘发作频率至少为每2-3周一次,哮喘每次发作之间无症状。此类患者通常需吸入色甘酸钠)或皮质激素以控制症状。由于无副作用,色甘酸钠为轻中度哮喘患者的首选药物。
1.3持续性哮喘：指大部分时候都有哮喘症状.此类患者通常需定时吸入皮质类固醇以控制症状,也需要长期服用支气管扩张药(施立稳/沙美特罗)。此类患者通常不需要每天服用皮质类固醇或氨茶碱。
2.纳入标准年龄：18-65岁；不吸烟者。
3.哮喘诊断
哮喘但不伴见其他严重复杂的因素如影响多系统功能的慢性疾病。
经肺功能检查诊断,患者有轻度至重度哮喘,在吸入支气管刺激剂后肺功能至少减少20%,并伴见气道其他症状如胸部不适、咳嗽、半夜咳嗽等。
4.排除标准
排除慢性重病如充血性心衰、肿瘤等,以及其他情况如怀孕。
5.测定血皮质醇(COR)
6.检测FF.V1
指一秒用力呼气容积：吸气至肺总量位后一秒之内快速呼出气量。
7.检测用力肺活量Forced vital capacity(FVC)
也称时间肺活量,是指将测定肺活量的气体用最快速呼出的能力,以升为单位测量,通常是检测呼吸量时的最基本方法。
8.FEV1/FVC (FEV1％)
健康成年人的FEV1%通常约为75-80%,在阻塞性疾病(哮喘,慢性阻塞性肺病,慢性支气管炎,肺气肿)患者中,FEVl通常减少,FVC通常也会由于呼气时气道过早关闭而降低,只是和FEV1降低的程度不同,例如,FEV1和FVC都降低,但FEV1由于增加的气道阻力而降低的更多,因为增加的气道阻力会影响呼出气流,这样就会导致FEV1%减少至<80%,甚至经常<45%。
9.资料收集程序
第1步：收集患者姓名、年龄、就诊日期、哮喘等级、电话、医疗卡号,患者随机分至第1组(观看令人愉悦的电影片段)或第2组(观看令人恐惧／悲伤的电影片段)。
第2步：基础脉率、呼吸频率、中医脉象、ACT得分。
第3步：输入患者的年龄、身高、体重和性别,校准呼吸量检测仪。
第4步：指导患者在尽力吸气后首先用力呼气并持续呼尽,记录FEV1、FEV1%。
第5步：患者排除外界环境干预,集中精神观看会引起悲伤恐惧或愉悦心情的电影片段,时长约8分钟。
第6步：观看电影结束后,再次指导患者在尽力吸气后首先用力呼气并持续呼尽,记录FEV1和FEV1%。
第7步：测量情绪干预后的呼吸频率和脉率。
第8步：询问患者观看电影够的反应和内心感觉。
第9步：询问患者个人史,如何时诊断为哮喘,第一次发生哮喘的时间以及当时生活中是否发生对其情绪有影响的事件,幼年的性格状况以及患者对于自己目前情绪状态的描述。
第10步：一个月后,在自体血穴位注射治疗一个完整周期后收集患者的ACT。
10.环境控制
空调环境保持室内温度恒定适中,控制空气湿度至适中。诊室安静,与其他患者隔离,保证观看电影片段的有效性。室内光线恒定。
11.医生的关怀
对所有患者医生保持同样的关注和热情,允许患者提问,患者有疑问时需帮助解决,但不向患者透露有关本研究性质的任何引导性信息。
12.统计学处理
所有数据用x±s表示,组间比较采用t检验,STATA10.0软件进行数据分析,P<0.05表示有统计学差异,P<0.01表示有显著差异。
成果：
一.理论研究结果
中医研究结果显示,《黄帝内经》是最早记载哮喘与情绪之间有相关性的著作,自此以后,中医历代典籍中有大量文献记载相关内容,并在《黄帝内经》的基础上,不断深入探讨和分析二者之间的相关性,从中医角度探讨了二者相关性的机制,提示随着中医学的发展,对哮喘的病因病机、症状、预后的认识越来越丰富,甚至对后世方剂学的发展都产生了重大影响,明代《医便》记载的五磨饮子治疗肺气郁闭型的实喘就是一个典型例子,该方中的五味中药木香、乌角沉香、槟榔、枳实、台乌药均为开郁降气之药,足以说明当时的医生已经充分认识到哮喘与情绪之间的相关性。
西医文献研究结果显示,与恐惧和悲伤等情绪相关的大脑中枢与哮喘之间有相互联系,这为《黄帝内经》乃至整个中医理论研究的领域创立了新的思路。同时研究显示,今后哮喘研究的新趋势将会以建立在中医阴阳理论和整体观基础上的系统生物学知识为依据,进一步分析和解释哮喘与情绪之间相关性的机理。
二.临床研究结果
组1患者在观看令人心情愉悦的电影片段前后呼吸频率发生明显变化,即观看电影后呼吸频率显著减慢,有统计学差异(P<0.05),说明良好的心情会对哮喘患者的呼吸状态有正面影响,这与观看电影后对患者的心理状态的询问结果是一致的,大部分患者均表示看完电影片段后心情愉悦,呼吸频率的减慢提示气机和缓,呼吸深度的增加；组2患者在观看令人心情悲伤／恐惧的电影片段前后呼吸频率亦发生明显变化,即观看电影后呼吸频率显著加快,有显著统计学差异(P<0.01),说明不良的心情会对哮喘患者的呼吸状态有负面影响,这与观看电影后对患者的心理状态的询问结果是一致的,大部分患者均表示看完电影片段后心情紧张沉重或忧伤,呼吸频率的加快提示呼吸深度的降低。
两组患者之间观看电影前后心率比率(即PR2/PRl)和呼吸比率(RR2/RR1)之间的相互比较结果均有显著统计学差异(P<0.01,P<0.01),均进一步说明良好的情绪状态对缓解哮喘症状有重要作用,而不良的情绪状态则会加重哮喘患者的症状。
组1患者两次ACT得分比较有显著统计学差异(P<0.01),其中ACT1是在患者进入研究后即刻测试的结果,而ACT2是在ACT1得分测试结束后马上观看电影,进行良好的情绪干预后并接受自体血穴位注射完整一个周期后再次检测得出的结果,ACT2得分较ACT1得分明显上升,说明良好的情绪干预及结合自体血穴位注射治疗较大地改善了患者的哮喘病情。
两组患者之间两次FEV1比率(即1stFEV1/2ndFEV1之间相互比较有统计学差异(P<0.05),说明由不同类型的电影片段引起不同的情绪状态后对哮喘患者的肺功能有较大影响,说明良好的情绪状态对增强哮喘患者一秒用力呼气容积有重要作用,而不良的情绪状态则会使哮喘患者的一秒用力呼气容积降低。
其余的各项比较虽均无统计学差异,但大部分可观察到数据均有上升或下降的趋势,分析其原因,主要是因为哮喘患者临床症状和肺功能的改善,是需要一个较长的过程才能明显体现出来的,短时间的情绪干预不可能很大程度地改变患者的各项指标,但指标改变的趋势仍可观察到,说明良好或不良情绪干预,分别有正面和负面改变患者哮喘状态和肺功能的作用趋势。
结论：
《黄帝内经》是中医理论的基石,本研究把《黄帝内经》首先提出的悲恐等情绪与哮喘发病之间有密切联系的观点在现代科学中发现了依据,即与哮喘相关的人体大脑中枢亦与悲伤、恐惧等不良情绪相关。同时,这对系统生物学领域的研究也有好处,即为其提供了情绪与哮喘之间具有相关性的观点,并希望未来有更多的系统生物学家进一步研究内经,研究中医,挖掘中医理论的实质,赋予中医理论的内涵更多的意义,因系统生物学在研究中医及《黄帝内经》方面最具潜力。
情绪状态在一定程度上会影响哮喘患者的肺功能和改变患者的哮喘状态,即良好的情绪对哮喘患者有一定的正面作用,能减慢患者的心率、呼吸频率,对患者的ACT及FEV1也有一定的改善作用；而不良的情绪状态,即本研究所讨论的悲伤和恐惧心理,则对患者有一定的负面影响,能加快患者的心率、呼吸频率,降低患者的FEV1等。
研究提示,中医所说的“神”在哮喘病的发病过程中起重要作用,临床治疗哮喘若忽视对患者“神”即情绪的正面调节和干预,将会在一定程度上影响疗效,而重视对患者不良情绪心理状态的调节,将会对促进临床疗效的提高起到重要作用,我想这就是本研究的目标之所在。
Objective
Huang Di Nei Jing discusses the role of shen disturbance as the basis of all diseases and that the emotions of fear and sadness are most predominant in the disease of asthma. While Western medicine has confirmed that depression and anxiety are associated with onset and exacerbation of asthma most studies in emotional research focus on non-explicit emotions but only dysregulation of anxiety and depression. This study was designed with specificity of nueurorespiratory function of sadness and fear in lung function and asthma control. Thus, this study hopes to contribute more support from a Western scientific basis for Huang Di Nei Jing.
Methods
1.Theoretical research
Articles from multiple disciplines of science (such as pulmonary medicine, immunology, neuroendocrinology, molecular psychology, systems science, etc.) were collected and analyzed according to certain questions such as:what is the validity of emotional dysregulation and asthma correlation, what is the mechanism of emotions and asthma, what are past and current research trends in asthma, explain systems biology research into asthma, what does Huang Di Nei Jing original articles say about emotions and asthma etc. Information was extracted and synthesized into a robust review of current thinking on emotional neuroregulatory functions of respiration in asthma. From this, a more thorough Western scientific model for asthma in Huang Di Nei Jing could be devised.
2. Clinical Research
38asthma patients were collected at Guangdong NanHai TCM hospital and shown affective video clips (8minutes) of either a content neutral/pleasant (Group 1) or sad/fearful (Group2) emotional stimulation based on research standard of affectively homogeneous picture series (IAPS). FEV1and FEV1%, breath rate, pulse rate, pulse quality, and social history were collected. One month later, ACT scores were collected.35patients were collected initially but due to inability to contact after one month, the patients were reduced to31in the study. Environment controls such as temperature regulation, clearing humidity, separation from distraction and doctors attention were regulated.
Results
1. Theoretic research
Found that there is a correlation with asthma and brain centers that are associated with fear and sadness which was synthesized information from different studies combined together. Therefore, creating new knowledge in the realm of Huang Di Nei Jing research. As well, this research found that the direction of asthma study could trend in the direction of systems biology to further explain the emotions and asthma mechanism.
2. Clinical research
When comparing Group1with Group2in a ratio, the patients in Group1had statistically higher FEV1when compared to Group2(p<0.05). By the value of the ratio, we could see the direction/trend of the changing of the observation point/index. When looking at the change in FEV1Group1's FEV1rose while Group2decreased. However, while there was a trend in rising and falling, it did not prove to be statistically valid with a (p>0.05) when looking at the rise and fall alone.
Conclusion
1. Theoretic research
Huang Di Nei Jing is the foundation of all Chinese Medicine. This study found new knowledge in the area of brain regions correlating with asthma control correlating with sadness and fear as was first put forth by Huang Di Nei Jing. As well, this could be useful in the area of research in Systems biology showing a level of connectedness and hope to attract systems biologist to further investigating Huang Di Nei Jing. This study helps to show that systems biology may hold great potential in scientifically explaining Huang Di Nei Jing.
2. Clinical Research
While there were some problems with the research statically in the FEV1changes in Group1and2, this could probably have to do with the some difficulties in the clinical setting such as patients'inability to fully comply with breathing technique required for spirometry machinery, attention span or interest in films, or other unknowns not foreseen. However, despite this, there was an obvious trend in lowering lung function in sadness and fear related movies. As well, the data proved that there is a statistical difference between the change when comparing Group1and Group2in a ratio where Group1FEV was higher than Group2.
引文
[1]王洪图.21世纪课程教材《内经讲义》 [M].北京：人民卫生出版社,2002,1：99-100.
[2]张登本.《黄帝内经白话通解》 [M].陕西：陕西人民出版社,1991：219-221.
[3]黎敬波,张小虎等.《内经临床运用》 [M].北京：人民卫生出版社,2011,199-201.
[4]Apfelbach R, B. C.. The effects of predator odors in mammalian prey species:a review of field and laboratory studies. Neurosci Biobehav Rev,2005,29:1123-1144.
[5]Barnes PJ, C. K. Inflammatory mediators in asthma. Pharmacol Rev,2001:49-84.
[6]Berntson, G. G. Heart rate variability:Origins, methods, and interpretive caveats. Psychophysiology,1997:623-648.
[7]Binyan, S. Cancer Treatment Prevention. Offete Enterprise.1991.
[8]Birnstiel S, L. T. Chronic corticosterone treatment maintains synaptic activity of CA1 hippocampal pyramidal cells:acute high corticosterone administration increases action potential number. Synapse,1995:117-124.
[9]Broeker, H. (n. d.). Cortisol Levels in Children With Asthma Symptoms. From essortment. com: http://www.essortment.com/cortisol-levels-children-asthma-symptoms-26192.html
[10]Calkins, S. G. Emotional reactivity and emotion regulation strategies and predictors of social behavior with peers during toddlerhood. Social Development,1999:310-41.
[11]Ching, K. Foundations of Traditional Chinese Medicine.. Retrieved 2011 йиЛ 23-8 from Creatspace.com:http:www.createspace.com/foundations,2010.
[12]Chrousos, G. P. The concepts of stress and stress system disorders. Journal of the American Medical Association,1992:1244-1252.
[13]De Kloet ER, V. E. Brain corticosteroid receptor balance in health and disease. Endocr Rev,19,1998:269-301.
[14]Dickerson SS, K. M. (n. d.). Acute stressors and cortisol responses:a theoretical integration and synthesis of laboratory research.130:355-391. Psychol Bull, Dorland's Illustrated Medical Dictionary. Elsivier.2004.
[15]ed.), X. X. The Enligsh-Chinese Encyclopedia of Practicle Traditional Chinese Medicine. Beijing:Higher Education Press.1989.
[16]Eisenberg, N. S. Shyness and children's emotionality, regulation, and coping: Contemporaneous, longitudinal and across-context relations. Child Development, 1998:767-790.
[17]Ekman, P. D. The Duchenne smile:Emotional expression and brain physiology II. Journal of Per-sonality and Social Psychology,1990:342-353.
[18]Flinn, M. V. Social economics of childhood glucocorticoid stress response and health.1997:33-53.
[19]Forster, R. E. The lung. Physiological basis of pulmonary function tests (3rd ed). Chicago:Year Book Medical Publishers.1986.
[20]Glaser R, K. S. Psychological stress induced modulation of interleukin 2 receptor gene expression and interleukin 2 production in peripheral blood leukocytes. Arch Gen Psychiatry,1990:707-12.
[2l]Granada A., W. P. Coupling governs entrainment range of circadian clocks. Molecular Systems Biology.2010.
[22]Grossman, P. K. Prediction of tonic parasympathetic cardiac control using respiratory sinus arrhythmia:The need for respiratory control.,1991.28,201-216. Psychophysiology
[23]H, S. Hormones and resistance. Berlin, New York:Springer-Verlag. K.., H. (2010). Harmonizing Traditional Chinese and Modern Western Medicine:A Perspective from the US. UCLA School of Medicine.1971
[24]Kaptchuck. Web That Has No Weaver.2011.
[25]Kaptchuk TJ, P. G. The need to act a little more'scientific':biomedical researchers investigating complementary and alternative medicine. Sociol Health Illn,2010:106-22.
[26]Keenan D, A. S. Quantifying Nonlinear Interactions within the Hypothalamo-Pituitary-Adrenal Axis in the Conscious Horse. Endocrinology, 2008:1941-1951.
[27]Klinnert, M., E, M., D, M., A, A., & N, B. A Multimethod Assessment of Behavioral and Emotional Adjustment in Children With Asthma. J. Pediatr. Psychol.,2000:35-46.
[28]Lehrer, P. M. Asthma and emotion:A review.. Journal of Asthma,1993:5-21.
[29]Lewitus G, S. M. Behavioral immunization:immunity to self-antigens contributes to psychological stress resilience. Nature:Molecular Psychiatry.2008.
[30]Lewitus G, S. M. Behavioral immunization:immunity to self-antigens contributes to psychological stress resilience Immunity to self for stress resilience. Nature: Molecular Biology,14,2010:532-536.
[3l]Li Leyi, W. C. Tracing The Roots of Chinese Characters 500 Cases,3 edition. Beijing, China:Beijing Language & Culture University Press.1997.
[32]Lipsitz, L. A. Dynamics of Stability:The Physiologic Basis of Functional Health and Frailty. Journal of Gerontology:BIOLOGICAL SCIENCES,2002:B115-B125.
[33]M, S. The emergence of a new science of the mind:immunology benefits the mind.2010.
[34]MG, M. Psychological factors aVecting pulmonary and rheumatologic diseases. Psychosomatics,1991,32:14-23.
[35]mtiaz, M. Pacemaking through Ca2+ stores interacting as coupled oscillators via membrane depolarization.2007.
[36]Myers, J. Proinflammatory cytokines and sickness behavior:implications for depression and cancer-related symptoms. Oncol Nurs Forum,2008:802-807.
[37]N Hepgul, V. M. Psychological and biological mechanisms of cytokine induced depression. Epidemiologia e Psichiatria Sociale,2010:98-102.
[38]Nisbett, R. The Geography of Thought, How Asians and Westerners Think Differently and Why. New York, New York, USA:Simon and Sheuster.2003.
[39]Phan, L., Wager, T., Taylor, S., & Liberzon, I. Functional Neuroimaging Studies of Human Emotions. CNS Spectr,2004:258-266.
[40]Raichur R., K. R. Effect of Meditation Training on Pulmonary Funciton Tests. Science and Technology,2 (11),2010:11-16.
[41]Rang, D. R. Pharmacology 5th ed. Churchill Livingstone.2003.
[42]Rosenkranz M, B. W. Review of psychosocial stress and asthma:an integrated biopsychosocial approach. PNAS,2005:13319-13324.
[43]Rosenkranz, M. B. Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation. PNAS,102(37),2005:13319-13324.
[44]Schwarts M, S. M. Disease, Protective autoimmunity Functions by Intracranial Immunosurvelliance to Support the Mind:The Missing Link Between Health and Disease. Nature:Molecular Psychiatry,2010:15,15-18.
[45]Schwartz. The emergence of a new science of the mind:immunology benefits the mind. Mol Psychiatry,2010:337-8.
[46]Schwartz, M. S. (Disease)Protective autoimmunity functions by intracranial immunosurveillance to support the mind:The missing link between health and disease Mol Psychiatry,2010:342-54.
[47]Stifter, C. D. Temperament and emotion regulation:the role of autonomic nervous system reactivity. Developmental Psychobiology,2011:266-279.
[48]Supplee, L. S. Emotion regulation strategies and later externalizing behavior among European and African American children. Development and Psychopathology,2009:393-415.
[49]Thompson, R. Emotion regulation and emotional development. Educational Psychology Review,1991:269-307.
[50]Urs Frey, T. B. Risk of severe asthma episodes predicted from fluctuation analysis of airway function. Nature, Vol 438,2005:667-670.
[51]US Department of Health and Human Services Public Health Services, National Institute of Health,. Executive summary:guidelines for the diagnosis and management of asthma. 1991.
[52]van Peer JM, R. K. Cortisol administration enhances the coupling of midfrontal delta and beta oscillations. International Journal of Psychophysiology.2007
[53]Wong M, D. C.-M. Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response. Nature:Molecular Psyciatry,13,2008:800-812.
[54]World Health Organization Definition. Definition of Asthma. Retrieved from http://www.who.int/respiratory/asthma/definition/en/.2010.
[55]Wright R, R. M. Review of psychosocial stress and asthma:an integrated biopsychosocial approach.1998:1066-1074.
[56]Xiaoming, Y. L. Health Preservation by Mental Means. Journal of Traditional Chinese Medicine,1993:144-147.
[57]ZC, L. The Mystery of Longevity. Beijing, China:Foriegn Language Press.1990.
[2]张登本.《黄帝内经白话通解》 [M].陕西：陕西人民出版社,1991：219-221.
[3]黎敬波,张小虎等.《内经临床运用》 [M].北京：人民卫生出版社,2011,199-201.
[4]Apfelbach R, B. C.. The effects of predator odors in mammalian prey species:a review of field and laboratory studies. Neurosci Biobehav Rev,2005,29:1123-1144.
[5]Barnes PJ, C. K. Inflammatory mediators in asthma. Pharmacol Rev,2001:49-84.
[6]Berntson, G. G. Heart rate variability:Origins, methods, and interpretive caveats. Psychophysiology,1997:623-648.
[7]Binyan, S. Cancer Treatment Prevention. Offete Enterprise.1991.
[8]Birnstiel S, L. T. Chronic corticosterone treatment maintains synaptic activity of CA1 hippocampal pyramidal cells:acute high corticosterone administration increases action potential number. Synapse,1995:117-124.
[9]Broeker, H. (n. d.). Cortisol Levels in Children With Asthma Symptoms. From essortment. com: http://www.essortment.com/cortisol-levels-children-asthma-symptoms-26192.html
[10]Calkins, S. G. Emotional reactivity and emotion regulation strategies and predictors of social behavior with peers during toddlerhood. Social Development,1999:310-41.
[11]Ching, K. Foundations of Traditional Chinese Medicine.. Retrieved 2011 йиЛ 23-8 from Creatspace.com:http:www.createspace.com/foundations,2010.
[12]Chrousos, G. P. The concepts of stress and stress system disorders. Journal of the American Medical Association,1992:1244-1252.
[13]De Kloet ER, V. E. Brain corticosteroid receptor balance in health and disease. Endocr Rev,19,1998:269-301.
[14]Dickerson SS, K. M. (n. d.). Acute stressors and cortisol responses:a theoretical integration and synthesis of laboratory research.130:355-391. Psychol Bull, Dorland's Illustrated Medical Dictionary. Elsivier.2004.
[15]ed.), X. X. The Enligsh-Chinese Encyclopedia of Practicle Traditional Chinese Medicine. Beijing:Higher Education Press.1989.
[16]Eisenberg, N. S. Shyness and children's emotionality, regulation, and coping: Contemporaneous, longitudinal and across-context relations. Child Development, 1998:767-790.
[17]Ekman, P. D. The Duchenne smile:Emotional expression and brain physiology II. Journal of Per-sonality and Social Psychology,1990:342-353.
[18]Flinn, M. V. Social economics of childhood glucocorticoid stress response and health.1997:33-53.
[19]Forster, R. E. The lung. Physiological basis of pulmonary function tests (3rd ed). Chicago:Year Book Medical Publishers.1986.
[20]Glaser R, K. S. Psychological stress induced modulation of interleukin 2 receptor gene expression and interleukin 2 production in peripheral blood leukocytes. Arch Gen Psychiatry,1990:707-12.
[2l]Granada A., W. P. Coupling governs entrainment range of circadian clocks. Molecular Systems Biology.2010.
[22]Grossman, P. K. Prediction of tonic parasympathetic cardiac control using respiratory sinus arrhythmia:The need for respiratory control.,1991.28,201-216. Psychophysiology
[23]H, S. Hormones and resistance. Berlin, New York:Springer-Verlag. K.., H. (2010). Harmonizing Traditional Chinese and Modern Western Medicine:A Perspective from the US. UCLA School of Medicine.1971
[24]Kaptchuck. Web That Has No Weaver.2011.
[25]Kaptchuk TJ, P. G. The need to act a little more'scientific':biomedical researchers investigating complementary and alternative medicine. Sociol Health Illn,2010:106-22.
[26]Keenan D, A. S. Quantifying Nonlinear Interactions within the Hypothalamo-Pituitary-Adrenal Axis in the Conscious Horse. Endocrinology, 2008:1941-1951.
[27]Klinnert, M., E, M., D, M., A, A., & N, B. A Multimethod Assessment of Behavioral and Emotional Adjustment in Children With Asthma. J. Pediatr. Psychol.,2000:35-46.
[28]Lehrer, P. M. Asthma and emotion:A review.. Journal of Asthma,1993:5-21.
[29]Lewitus G, S. M. Behavioral immunization:immunity to self-antigens contributes to psychological stress resilience. Nature:Molecular Psychiatry.2008.
[30]Lewitus G, S. M. Behavioral immunization:immunity to self-antigens contributes to psychological stress resilience Immunity to self for stress resilience. Nature: Molecular Biology,14,2010:532-536.
[3l]Li Leyi, W. C. Tracing The Roots of Chinese Characters 500 Cases,3 edition. Beijing, China:Beijing Language & Culture University Press.1997.
[32]Lipsitz, L. A. Dynamics of Stability:The Physiologic Basis of Functional Health and Frailty. Journal of Gerontology:BIOLOGICAL SCIENCES,2002:B115-B125.
[33]M, S. The emergence of a new science of the mind:immunology benefits the mind.2010.
[34]MG, M. Psychological factors aVecting pulmonary and rheumatologic diseases. Psychosomatics,1991,32:14-23.
[35]mtiaz, M. Pacemaking through Ca2+ stores interacting as coupled oscillators via membrane depolarization.2007.
[36]Myers, J. Proinflammatory cytokines and sickness behavior:implications for depression and cancer-related symptoms. Oncol Nurs Forum,2008:802-807.
[37]N Hepgul, V. M. Psychological and biological mechanisms of cytokine induced depression. Epidemiologia e Psichiatria Sociale,2010:98-102.
[38]Nisbett, R. The Geography of Thought, How Asians and Westerners Think Differently and Why. New York, New York, USA:Simon and Sheuster.2003.
[39]Phan, L., Wager, T., Taylor, S., & Liberzon, I. Functional Neuroimaging Studies of Human Emotions. CNS Spectr,2004:258-266.
[40]Raichur R., K. R. Effect of Meditation Training on Pulmonary Funciton Tests. Science and Technology,2 (11),2010:11-16.
[41]Rang, D. R. Pharmacology 5th ed. Churchill Livingstone.2003.
[42]Rosenkranz M, B. W. Review of psychosocial stress and asthma:an integrated biopsychosocial approach. PNAS,2005:13319-13324.
[43]Rosenkranz, M. B. Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation. PNAS,102(37),2005:13319-13324.
[44]Schwarts M, S. M. Disease, Protective autoimmunity Functions by Intracranial Immunosurvelliance to Support the Mind:The Missing Link Between Health and Disease. Nature:Molecular Psychiatry,2010:15,15-18.
[45]Schwartz. The emergence of a new science of the mind:immunology benefits the mind. Mol Psychiatry,2010:337-8.
[46]Schwartz, M. S. (Disease)Protective autoimmunity functions by intracranial immunosurveillance to support the mind:The missing link between health and disease Mol Psychiatry,2010:342-54.
[47]Stifter, C. D. Temperament and emotion regulation:the role of autonomic nervous system reactivity. Developmental Psychobiology,2011:266-279.
[48]Supplee, L. S. Emotion regulation strategies and later externalizing behavior among European and African American children. Development and Psychopathology,2009:393-415.
[49]Thompson, R. Emotion regulation and emotional development. Educational Psychology Review,1991:269-307.
[50]Urs Frey, T. B. Risk of severe asthma episodes predicted from fluctuation analysis of airway function. Nature, Vol 438,2005:667-670.
[51]US Department of Health and Human Services Public Health Services, National Institute of Health,. Executive summary:guidelines for the diagnosis and management of asthma. 1991.
[52]van Peer JM, R. K. Cortisol administration enhances the coupling of midfrontal delta and beta oscillations. International Journal of Psychophysiology.2007
[53]Wong M, D. C.-M. Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response. Nature:Molecular Psyciatry,13,2008:800-812.
[54]World Health Organization Definition. Definition of Asthma. Retrieved from http://www.who.int/respiratory/asthma/definition/en/.2010.
[55]Wright R, R. M. Review of psychosocial stress and asthma:an integrated biopsychosocial approach.1998:1066-1074.
[56]Xiaoming, Y. L. Health Preservation by Mental Means. Journal of Traditional Chinese Medicine,1993:144-147.
[57]ZC, L. The Mystery of Longevity. Beijing, China:Foriegn Language Press.1990.