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情绪、压力和心理qingxuyalihexinli

压力管理:磷脂酰丝氨酸、益生菌、B族维生素

时间:2021-03-03 12:45 阅读:509 来源:朴诺健康研究院

目  录

一、概述

二、引言

三、身体如何应对压力?

四、压力如何导致健康问题?

五、慢性压力对健康有什么影响?

六、判断压力是否会影响你的健康

七、暂时缓解压力的药物

八、缓解压力的生活方式和行为技巧

九、食物和压力-饮食如何影响压力?

十、缓解压力的自然和综合干预措施

十一、参考文献


一、概述

摘要和速览

  1. 压力是一种适应性反应,短期内是健康的。但是,慢性的、低水平的心理压力在现代社会非常普遍,会导致许多健康问题。在2020年席卷全球的COVID-19大流行就是一个例子,它是导致全球大部分人长期承受巨大压力的一个因素。

  2. 本方案将帮助您了解身体对压力的反应,以及长期压力对健康的损害。你将学习一些实验室测试,这些测试有助于确定压力是否影响你的健康,并发现几种营养素(如茶氨酸),以及饮食和生活方式的改变,可以促进健康的压力反应。

什么是压力?

压力通常发生在外部刺激干扰身体生理过程的动态平衡时。一个被称为HPA轴的特殊信号网络协调着身体的应激反应。

急性压力有助于激发身体对即时、短暂的威胁作出反应。间歇性的轻微压力,如运动,是健康的,并促进积极的适应性变化。然而,慢性压力会导致不适应反应和HPA轴功能失调。这可能通过扰乱昼夜节律、促进炎症、改变微生物组和引起表观遗传变化而导致许多健康问题。

自然干预,如调理素,L-茶氨酸,B族维生素,和omega-3脂肪酸可能有助于缓解压力和恢复正常的HPA轴功能。

我如何确定压力是否影响了我的健康?

  1. 实验室检查(包括皮质醇、脱氢表雄酮[DHEA]、唾液α-淀粉酶和免疫球蛋白A[IgA])

  2. 心率变异性

什么样的饮食和生活方式改变可以帮助缓解压力?

  1. 认知行为疗法

  2. 冥想和专注当下

  3. 锻炼

  4. 保持良好的睡眠卫生、充足的睡眠时间和一致的睡眠模式

  5. 保持社交联系,并经常与朋友和亲人互动,即使在环境(如由于COVID-19大流行导致的社交距离)限制面对面的互动时,也可以使用社交媒体平台

  6. 维持性激素平衡

  7. 多吃水果和蔬菜

  8. 定期吃早餐

  9. 尽量减少咖啡因和酒精的摄入

药物能帮助缓解压力吗?

许多情况下,饮食和生活方式的干预措施可以管理压力。然而,在更严重的情况下,当压力导致其他疾病,如焦虑或失眠,药物可能适合短期使用,以暂时解决压力相关的问题。重要的是要明白,药物不能消除压力或压力的原因,而只是提供暂时缓解一些压力所造成的症状。

  1. 抗抑郁和抗焦虑药物,如选择性5-羟色胺再摄取抑制剂(SSRIs)(如百忧解和唑洛夫)

  2. β受体阻滞剂(如普萘洛尔)

  3. 镇静剂,如苯二氮卓类(如安定和克洛宁)

  4. 氢化可的松

什么样的自然干预可以帮助缓解压力?

  1. B族维生素。维生素B缺乏与多种神经精神疾病有关。补充B族维生素已被证明可以缓解压力和支持正常的HPA轴功能。

  2. 维生素C。维生素C摄入量和循环水平低与抑郁和焦虑症状相关。通过补充维生素C来提高维生素C水平已经被证明可以减轻症状。

  3. ω-3脂肪酸。在鱼油中发现的omega-3脂肪酸,如二十碳五烯酸(EPA)和二十二碳六烯酸(DHA),可能有助于预防和治疗压力、焦虑和抑郁。

  4. L-茶氨酸。茶氨酸,一种在茶叶中发现的氨基酸,已经被证明可以减少感知的压力和压力反应的生理指标。

  5. 生物活性乳肽。牛奶中的肽,如α-乳清蛋白和酪蛋白,可以支持健康的神经功能,改善情绪,促进睡眠。

  6. 益生菌和益生元。益生菌和益生元可以改善肠道细菌的平衡,对应激反应有积极影响。益生菌可以降低压力反应性和焦虑,改善情绪、记忆和认知。

  7. 调理素。草本调理素有助于维持体内平衡,可以用来缓解疲劳,改善认知功能和情绪,并支持免疫系统。

    o木兰和黄柏。已发现这种草药组合,以减少压力和压力相关的体重增加。

    o圣罗勒茶。一些临床和临床前研究已经证明了圣罗勒的能力,以改善情绪和认知。

    o印度人参。已经证明印度人参可以缓解压力,改善与压力相关的饮食行为,促进减肥。

    o柠檬香膏。柠檬香膏被发现可以改善情绪和认知,缓解焦虑和失眠的症状。

    o可能有助于缓解压力的其他调理素包括巴可帕、藏红花、人参、红景天和冬虫夏草等。

  8. 其他自然干预可能有助于缓解压力,包括磷脂酰丝氨酸、L-色氨酸、褪黑素和脱氢表雄酮(DHEA)


二、引言

在进化的过程中,人体已经开始依赖急性应激反应来克服短期逆境。但人类的生理学根本不适应相对现代的无休止的低水平压力现象。因此,我们现在面临着大量的健康问题,慢性压力是一个促成因素。1,2

许多类型的事件和环境都会被认为是有压力的。自然灾害、暴力、战争和创伤性事故等事件对其影响的每个人都有压力,是与压力相关的心理健康问题的重要原因,可影响整个社区团体。393其他个人事件,如离婚、失业、严重或慢性疾病以及丧亲之痛对人的影响各不相同,但却是个人慢性压力的常见原因。394-397

2019-2020年的病毒性大流行COVID-19(冠状病毒病2019的缩写)给世界各地的人们和社会带来了许多潜在的压力环境。398以往传染病爆发后收集到的信息表明,与这些事件相关的干扰可能会导致社区和个人的持久社会心理压力问题。这些干扰包括日常生活的改变、疾病或对疾病的恐惧、工作中断、经济不安全、孤独、悲伤和失落、对未来的不确定性和绝望感。399对于医护人员和护理人员来说,压力感往往更为强烈。398,400一份来自大型药店的福利管理机构的报告指出,焦虑、抑郁和失眠的处方药在2020年3月猛增了21%。401

慢性应激的一个关键生理特征是下丘脑-垂体-肾上腺(HPA)轴的失调,HPA轴是大脑和身体中的一个信号中心网络,调节我们对应激的生理反应。HPA轴的正常激活对于对应激源的健康适应性反应是必要的,但慢性激活会导致应激激素皮质醇的释放和活性发生变化,从而导致应激相关疾病。2,3 HPA轴与中枢神经系统之间的相互作用,免疫系统和肠道微生物群对压力对整体健康的影响非常广泛。4,5

好消息是,健康的生活方式和坚持健康的饮食可以增强对慢性压力有害影响的抵抗力。4-6在本方案中,你将学习慢性压力如何导致健康问题,以及如何提高自己应对压力的能力,加强自己对抗现代社会压力带来的负面健康影响。


三、身体如何应对压力?

战斗或逃跑反应

压力通常发生在外部刺激扰乱机体生理过程的动态平衡时。压力,或“战斗或逃跑”的反应开始于大脑,在那里感知到的威胁会触发来自下丘脑的促肾上腺皮质激素释放激素的释放(CRH)。这会刺激位于下丘脑下方的垂体前叶,使促肾上腺皮质激素(ACTH)释放到血液中。ACTH作用于肾上腺皮质,促进皮质醇和活性较低的糖皮质激素、皮质酮以及另一种称为脱氢表雄酮(DHEA)的肾上腺激素的产生和释放。8

神经系统和肾上腺之间的信号网络,称为下丘脑-垂体-肾上腺(HPA)轴,部分由负反馈机制调节,通过负反馈机制,皮质醇血浓度升高抑制CRH和ACTH的释放。3,9

压力也直接参与交感神经系统在称为蓝斑的大脑区域的信号。肾上腺髓质和交感神经末梢释放的儿茶酚胺类神经激素(肾上腺素和去甲肾上腺素)具有生理作用,旨在帮助身体对压力环境作出反应和适应。尽管它往往与HPA轴协同工作,交感神经系统也能独立地激活应激反应。3,9

急性压力

作为应激反应的介质,皮质醇和儿茶酚胺对整个身体都有深远的影响(见表1)。当高度急剧上升时,它们帮助身体做好躲避危险的准备。例如,心输出量增加以支持更强的血流;血糖水平增加以满足更高的能量需求;瞳孔扩大以允许更多的视觉输入;警觉和认知能力增强;消化和生殖功能由于在短期内不是必需的而受到抑制。9

表1:急性压力的潜在原因

生理应激源急性适应性应激反应
低血糖水平10,11

儿茶酚胺刺激碳水化合物储存的分解和蛋白质和脂肪转化为葡萄糖

皮质醇抑制非中枢神经系统组织使用葡萄糖

低血压水平3,12

儿茶酚胺刺激血管收缩

皮质醇增加钠和水在肾脏的保留

低氧饱和3,13,14儿茶酚胺刺激大脑呼吸中枢增加呼吸,增加心率和收缩强度,并选择性地收缩血管
氧化应激15儿茶酚胺和皮质醇改变细胞代谢以恢复氧化还原平衡
炎症因子1,16儿茶酚胺和皮质醇调节免疫活动

慢性压力

急性压力反应可导致积极的适应效应,但当HPA轴和蓝斑被慢性激活时,其效应变得不适应:对慢性或重复压力的反应可能变得迟钝,但同时,对新应激源的敏感性可能增强,17失调的应激反应导致皮质醇和儿茶酚胺产生和/或受体对它们的反应模式发生改变。3,9慢性压力甚至可能改变大脑结构。18此外,慢性压力引起的HPA轴损伤似乎抑制DHEA的产生和释放,即使在急性压力情况下也是如此,19这一点很重要,因为DHEA反对皮质醇的某些作用:它保护神经并刺激神经连接的发育,具有对抗和平衡皮质醇的免疫调节作用,并可防止皮质醇引起的代谢紊乱。8对慢性压力反应的确切性质取决于个体人格特征、性别、年龄、生活经历、遗传和表观遗传因素等。3

社会孤立和孤独的压力负担

2018年1月,英国政府宣布成立孤独部。这一决定是基于2017年的一份报告,该报告发现900万英国人经常或总是感到孤独,以及越来越多的人认识到社会孤立和孤独会对身心健康造成损害。20,21

对于心血管疾病和心理健康问题来说,孤独感(一种心理压力)与健康状况不佳之间联系的证据尤其明显。20-23尤其是在老年人中,孤独感与认知能力下降和痴呆症、医疗保健使用、疗养院入住等因素有关,最近的一项研究表明孤独对健康的影响可能是通过改变HPA轴和交感神经系统对压力的反应来介导的。与压力反应本身一样,个体对社会孤立的反应也各不相同。24

孤独对整个社区健康的影响可能是COVID-19大流行最重要的长期影响之一。在整个大流行期间,社会隔离、自我隔离和检疫被广泛用作减缓传染性冠状病毒社区传播的策略。虽然这些措施在以前的传染病爆发中是有帮助的,而且似乎减缓了新的COVID-19病例的发病率,但是它们可以增加孤独、绝望和绝望的感觉,特别是在那些没有强大社会网络的人中。在一项研究中,在中国,由于接触冠状病毒或疑似轻度感染而自我隔离14天的人中,社会支持和联系度的低程度与压力和焦虑感的增加有关。403另一份报告指出,强大的社会支持与医疗保健中压力恢复能力的提高之间存在关系,还有证据表明,缺乏社会联系可能会增加病毒性呼吸道感染的风险和严重程度。在一项研究中,感觉被支持和拥抱都与减少压力和降低病毒性感冒的风险有关。在那些社会支持水平较低的人中,压力增加与感染风险增加有关。405这些研究结果强调了对于处于最高隔离和孤独风险的人,采取措施增加他们的社会支持而不增加他们感染风险的重要性。


四、压力是如何导致健康问题的?

长期的压力与许多慢性疾病相关,这些疾病影响到身体的所有器官系统。当生活的压力对心理和身体造成伤害时,慢性疾病本身就成为压力的来源。压力和疾病之间的双向关系造成了心理和身体健康的恶性循环,而且很难克服。2

压力与昼夜节律

HPA轴受脑内昼夜信号的密切调控。这种昼夜节律信号受昼夜(光和暗)周期、进食时间模式和其他可能尚未发现的因素的影响。正常情况下,皮质醇水平在早晨醒来后不久达到峰值,在就寝时间前后最低。通过作用于全身的受体,皮质醇将昼夜节律强加给其他生理功能。17,25

许多研究表明,昼夜节律的紊乱,如轮班工作、睡眠呼吸暂停和其他睡眠障碍,与心血管疾病、2型糖尿病、肥胖和一系列与年龄有关的疾病等健康问题有关,27昼夜节律紊乱甚至可能与寿命缩短有关。28慢性压力似乎损害了HPA轴的昼夜节律控制,这可能导致晚上皮质醇水平过高或早晨皮质醇水平降低。29这些皮质醇释放的功能失调模式可能是慢性压力和昼夜节律紊乱对身心健康产生负面影响的潜在因素。30

压力与免疫系统

慢性压力影响长期健康的一个重要途径是通过失调的免疫信号。尽管皮质醇最为人所知的是其免疫抑制作用,但其对免疫的影响是复杂的,刺激免疫的某些方面并抑制其他方面。1,25一种被称为糖皮质激素抵抗的现象,即组织和细胞对皮质醇的反应变弱,是由于慢性压力导致皮质醇水平长期升高所致。31,32

慢性压力诱导的免疫功能紊乱导致对感染和癌症的免疫保护降低。慢性压力,特别是当它涉及人际关系或工作时,与呼吸道感染(如流感和普通感冒)的风险增加一直相关。406-408研究还表明,持续高水平的感知压力和皮质醇与病原体的炎症反应增强相关,至少部分原因是糖皮质激素抵抗。这种炎症反应的增强导致对感染、组织损伤和症状严重性的易感性增加。408-410在一项研究中,皮质醇生成量较高的参与者不仅增加了患普通感冒的风险,而且病毒消失的天数也增加了,这表明感染持续时间更长,可能具有传染性。411慢性压力的促炎作用可能与COVID-19和其他高致病性冠状病毒有关,后者通过引发称为“细胞因子风暴”的强大炎症免疫反应而导致毁灭性的肺组织损伤。412

压力也被认为是内在炎症状态(如过敏性和自身免疫性疾病),同时也被认为是低水平全身炎症(如心脏病和糖尿病)相关疾病的促发因素。1,33一旦炎症开始,它通过细胞因子(免疫系统的小信号蛋白)对下丘脑、垂体和肾上腺皮质的作用维持应激反应。25,34

压力与微生物群

慢性压力可能通过与肠道微生物组的相互作用影响健康——肠道中有数万亿微生物。通过其与神经系统信号的关系,通常被称为“肠道-微生物-脑轴”,其调节免疫系统的能力,健康的微生物组似乎是必不可少的调节应激反应和防止过度刺激的HPA轴。与慢性压力相关的条件已被证明会改变肠道微生物群落的组成。微生物的不平衡,反过来,可以导致肠道和全身炎症和异常的神经信号,可以触发HPA激活。35-38

压力的表观遗传学

在生命早期暴露于压力可以改变整个生命的应激反应和复原力。部分原因可能是压力对大脑和肾上腺发育的影响;另一个重要因素是表观遗传学。表观遗传学是指环境诱导的基因表达模式的修改(相对于基因序列的变化)或控制基因如何用于指导细胞中的蛋白质合成的因素。这些变化是持久的,但可因未来情况而逆转。39

由产前和早期生活应激引起的表观遗传变化导致HPA轴的高反应性,并增加成年期出现神经精神问题的风险,如抑郁、焦虑和创伤后应激障碍。39-41新兴的研究表明,压力引起的表观遗传学变化也可能发生在成年期,影响HPA轴的反应性,增加压力相关的健康问题的脆弱性。42此外,由于表观基因组是由父母双方传给后代的,因此暴露在强烈或持续的压力下可能会影响多代人的复原力和健康。41,43,44

兴奋效应-间歇性轻度压力的好处

虽然慢性压力具有毒性作用,最终会缩短寿命,但短期暴露在压力下可以促进适应性策略的发展,从而支持健康和长寿。发展应对机制以应对轻微压力的过程被称为兴奋,这是一种建立抵抗更大压力的能力的方法。另一种表达兴奋概念的方式是一个常见的短语,“没有杀死你的东西会让你更强大。”45,46

运动是一种刺激压力的例子:它通过增加体温、机械需求、营养和氧气需求以及自由基产生引起压力。46定期适度运动引起的细胞对压力的反应,可以在广泛的健康益处和更长的寿命中反映出来。另一方面,剧烈运动,如持续18至24小时而不间断的锻炼,会耗尽身体的适应能力,损害健康,并可能缩短寿命。45,46中等热量限制也会带来类似的好处:适应较低的能量供应涉及新陈代谢、免疫和神经内分泌功能的改变,这些功能与健康衰老有关,并可能延长寿命。47,48


五、慢性压力对健康有什么影响?

慢性压力会对全身健康产生相当大的影响。它可以导致许多疾病的发生或恶化。下面的讨论重点介绍了一些更常见的情况,这些情况通常是慢性压力造成的。

心血管疾病

慢性压力对健康影响最广的是心脏病。通过皮质醇和儿茶酚胺的作用,以及通过睡眠障碍扰乱昼夜节律,慢性压力已被证明会损害心脏功能的神经系统调节,49并可导致高血压、心律失常,血管炎症导致动脉粥样硬化和血凝块。50长期的家庭和工作压力显然与冠心病和心脏事件(包括心脏病发作和中风)的风险增加有关。12,51最近的一项荟萃分析强调了工作压力对心脏病风险的影响:分析了研究人员发现,超过74万名男性和女性,每周工作55小时或以上的人与工作时间较少的人相比,患冠心病的风险增加12%,患中风的风险增加21%。52

急性压力也会对心脏造成威胁。研究指出,在地震和世界杯足球锦标赛等剧烈应激事件后,心脏病发作的发生率增加。53 Takotsubo心肌病是一种心肌突然衰弱的疾病,类似于心脏病发作或心绞痛的症状,具有潜在的致命性,是急性应激对心脏危险的另一个例子。Takotsubo心肌病也被称为应激性心肌病、心碎综合征和心尖气球综合征,通常发生在严重的身体或精神创伤后几个小时,最常见于绝经后妇女。54,55

精神和神经疾病

慢性压力与几种常见的神经精神疾病密切相关,包括抑郁、焦虑、痴呆和阿尔茨海默病。

引起突然的、长时间的生活中断的情况会加剧感知的压力和相关的情绪反应。这些压力会引发睡眠障碍和心理问题,如焦虑和抑郁,在某些情况下,这些问题会持续很久。413,414,新冠肺炎病毒大流行就是这种压力源的一个例子。这一流行病的各个方面,如长期隔离、害怕疾病、沮丧、厌倦、经济紧张、食物和其他供应不足、缺乏可靠的信息和耻辱感,都是造成压力和心理问题的原因。对许多人来说,家庭禁闭也妨碍了诸如锻炼和社交之类的减压活动。413另一方面,获得准确的信息,如洗手或戴面罩等预防措施,强烈的社会支持,以及获得高质量的睡眠,都与新冠肺炎危机期间压力水平降低和焦虑症状减少有关。403,414,416,417

社交媒体与COVID-19大流行期间的压力

2019-20年的COVID-19流感大流行经历是由24小时的新闻周期和社交媒体塑造的。谣言和错误信息在网上盛行,传播恐慌和混乱的速度快于冠状病毒,助长了恐惧、阴谋论和囤积。418-420错误信息造成了疾病统计、治疗、预防措施和疾病传播方面的混乱;这也增加了压力的负担。421反复接触有关危机的新闻,以及媒体放大相互矛盾和不准确的信息,导致压力和焦虑加剧,有些人称之为“标题压力障碍”。419,422与任何重复压力一样,与新闻暴露有关的压力对健康造成损害。422限制新闻消费的数量,强调高质量、公正、有信誉的消息来源似乎是消除这种压力的最佳方法。419

社交媒体在减轻压力和利用有用的集体行动方面也可以发挥积极作用。 社交媒体技术提供了许多机制,可让人们保持社交联系,同时保持身体上的距离。促进社交联系的应用程序和平台虽然不能取代面对面的互动,但可以帮助缓解孤独和孤独的压力。423社交媒体还可以用来提供安慰和有效的建议,交流准确的信息,并解释社区社交疏远或就地避难命令背后的理由。418,423通过这些方式,社交媒体可以支持控制流行病的工作,同时减少压力并积极影响心理和身体健康。

由压力相关信号触发的大脑炎症是将压力与神经精神疾病联系起来的一个重要因素。57在阿尔茨海默病中,压力相关免疫功能障碍似乎削弱了大脑清除β样淀粉的能力,而β样淀粉是一种参与阿尔茨海默病发展和进展的蛋白质。58,59此外,长期高皮质醇水平是慢性压力的标志,可触发神经元结构的改变,降低大脑可塑性(建立新神经元连接的能力)。56早期生活、重复性或慢性压力也可降低神经生长因子的活性,尤其是脑源性神经营养因子(BDNF),BDNF参与新神经连接的形成。60-62低水平的脑源性神经营养因子与心境障碍以及学习记忆障碍有关。62此外,这些应激相关的变化可能是表观遗传编码的,以持久的方式改变神经系统的可塑性和功能。63

癌症

越来越多的证据表明,应激反应中的神经激素可促进癌症的发生和发展。64,65此外,慢性压力可能与吸烟、滥用药物、暴饮暴食和减少体力活动等行为有关,这些行为会增加患某些癌症的风险,67应对癌症诊断、症状和治疗对某些人来说本来就是极度紧张的,68,69然而高压力负担可能会对癌症治疗和预后产生负面影响。64,70,71

压力影响癌症的机制可能是多方面的,但其基础可能是免疫失调,表现为免疫监视功能下降和全身炎症。HPA轴失调抑制了对癌症的免疫防御,慢性全身炎症创造了支持癌症发生、发展和转移的条件。72,73炎症可能源于其他应激引起的后遗症,包括体重增加和代谢紊乱、肠道菌群破坏,以及表观遗传改变72;反过来,炎症也可能参与这些过程。74此外,压力可能通过生物活动的昼夜节律失调而影响癌症的发展。29,75

代谢紊乱:为什么压力使减肥变得困难?

压力反应最重要的功能之一是确保有足够的能量来应对压力环境。在急性压力发作期间,食欲被抑制,为战斗或逃跑保留注意力,额外的能量以葡萄糖的形式从储存的脂肪和碳水化合物中释放出来。然而,在慢性压力条件下,食欲通常会上调,对高糖、高脂肪、高热量食物的渴求会因长期过度刺激HPA轴及其与调节食欲的神经激素(如ghrelin和leptin)的复杂相互作用而加剧。原因尚不完全清楚,作为对慢性压力的反应,食欲增加在女性中比男性更为明显。10,76

更糟糕的是,慢性压力和HPA轴失调与胰岛素抵抗和2型糖尿病以及脂肪组织生长和肥胖有关。77,78在一项研究中,唾液皮质醇测试显示,皮质醇释放的昼夜节律紊乱与体重指数(BMI)和腰围相关,腰围是衡量内脏脂肪的一种指标,是代谢综合征的心血管危险因素之一。79长期压力的这些代谢后果会促进广泛的炎症信号,从而损害血管,增加心血管风险。80,81全身炎症也会影响神经系统,导致情绪和认知障碍,并造成HPA轴激活增加的恶性循环。10,82

尽管人们普遍认为慢性压力会导致甲状腺功能减弱,但截至本文撰写之日,几乎没有证据支持这一观点。在一项研究中,患有明显甲状腺功能减退症的成人的头发皮质醇水平高于健康成人,并且与较高的体重和BMI相关;然而,在患有亚临床甲状腺功能减退症的参与者中,他们的实验室检查值正常至轻度异常,可能还有甲状腺功能减退症症状,头发皮质醇水平与健康受试者没有显著差异。83初步研究的结果表明,压力可能导致自身免疫性甲状腺功能减退症的发生;然而,这些研究的回顾无法证实这种联系。84另一方面,动物研究的证据表明甲状腺功能减退症可能触发HPA轴失调,慢性时,减少肾上腺输出量。85,86

压力可能使健康状况恶化

几乎任何健康状况都会受到压力的负面影响。除了已经讨论过的,以下是压力可能影响的一些紊乱和疾病:

  1. 哮喘87

  2. 特应性皮炎88

  3. 自身免疫性疾病89

  4. 慢性疲劳综合征90

  5. 上下呼吸道感染91

  6. 不孕92

  7. 肠易激综合征93

  8. 偏头痛94

  9. 疼痛障碍95,96

  10. 性功能障碍97


六、确定压力是否会影响您的健康

尽管慢性压力的影响因人而异,但一些实验室和临床评估可以帮助确定压力是否可能导致健康问题。 可能有助于评估压力影响整体健康的客观测试包括皮质醇,DHEA水平,唾液α-淀粉酶和免疫球蛋白A(IgA)水平以及心率变异性。

皮质醇

测量皮质醇水平有助于评估HPA轴功能。 唾液,血液,尿液和头发中的皮质醇水平已被证明是肾上腺皮质醇输出的可靠指标。98,99这些测试方法广泛可用,有时可作为HPA轴功能的指标。 通常,在严重抑郁症中,反映HPA轴过度活动的长期皮质醇输出增加是典型的,而在慢性疲劳综合症和创伤后压力中,皮质醇输出降低的反映出HPA轴的活动不足是典型的。100

?唾液皮质醇是一种非侵入性测试,可能有助于确定肾上腺功能的昼夜节律是否完整或紊乱。深夜唾液皮质醇有时被用来诊断库欣综合征(一种过度接触皮质醇或类似皮质醇的药物引起的疾病)。然而,在一天中多次测量皮质醇水平的测试,创造出一条反映皮质醇释放日变化的曲线,在评估压力方面可能有更广泛的用途。101,102一项研究综述发现,皮质醇日变化曲线平坦与健康状况较差相关。103

?皮质醇水平随着年龄的增长而逐渐升高,并受到性别的影响,尤其是在青春期前后和老年人中。尽管每个实验室都确定了自己的参考范围,但成人唾液皮质醇峰值水平(醒来后第一小时内)似乎在1.8至26 nmol/L之间,夜间谷值水平(醒来后约16小时)在0.2至3.5 nmol/L之间。104

?头发皮质醇浓度是一种新的非侵入性方法,用于评估数月到数年的长期皮质醇暴露。由于压力水平会随时间而波动,皮质醇通常是在离头皮最近的三厘米头发中测量的(反映了前三个月HPA轴的活动)。105头皮头发中的皮质醇浓度随着心理和生理压力的不同而变化,与感知压力和压力相关的症状和疾病相关,包括肥胖、代谢综合征和心血管疾病。99,106

唾液α-淀粉酶和免疫球蛋白A(IgA)

α-淀粉酶是唾液腺和胰腺中产生的一种淀粉消化酶。唾液α-淀粉酶的产生在交感神经系统的刺激下增加,从而触发“战斗或逃跑”反应,并在压力反应中起关键作用。另一方面,唾液蛋白如α-淀粉酶和抗体免疫球蛋白A(IgA)的产生受到控制静息机体功能的副交感神经系统的抑制。因此,唾液α-淀粉酶和唾液IgA被认为是神经系统调节平衡的标志物和压力的客观指标。107-109

大量研究表明,由于生理和心理压力,α-淀粉酶会增加,在焦虑等与压力相关的情况下,α-淀粉酶的水平也很高。107,110有时,α-淀粉酶会与唾液皮质醇(反映HPA轴活动)一起测试,以提供更全面的压力评估。尽管不是常规进行,但有证据表明,这种唾液测试的结合可能有助于无创性和客观地评估压力对慢性病患者的作用111和监测减压治疗的效果。112

唾液分泌型IgA(sIgA)也被认为是压力的标志。许多研究表明,急性压力可增加这种重要抗体的水平。113-115然而,慢性压力时,sIgA似乎耗尽,唾液水平下降,116,117可能增加患口腔、胃肠道疾病的风险,和呼吸道感染。118唾液sIgA的解释有些挑战性,因为它对口腔环境中其他因素的敏感性。119

唾液sIgA和α-淀粉酶检测是商业上可获得的,并且经常被综合医疗保健提供者推荐和解释。一般来说,这些唾液测试的标准化和更多关于干扰其解释的因素的信息,如吸烟、饮食和药物使用,将有助于提高其有用性和可接受性。108,119,120

脱氢表雄酮

脱氢表雄酮(DHEA)是一种肾上腺激素,在许多组织中有对抗皮质醇的某些作用。急性压力可增加健康人DHEA和皮质醇的产生,但慢性压力与低DHEA和高皮质醇的产生有关。8在一项研究中,DHEA-S(DHEA硫酸盐,与工作相关压力最低的健康成年人相比,工作相关压力最高的健康成年人的DHEA形式(通常在血液中测量)降低了23%。121皮质醇和DHEA产生之间的平衡也随着年龄的增长而显著变化:DHEA的释放在老年人中最低,有人认为,在DHEA含量下降的情况下,皮质醇的作用不受抑制,这可能导致与年龄和压力有关的疾病。8,122,123

有证据表明,通常与最佳健康状况相对应的DHEA-S血液水平男性为350-500微克/分升,女性为275-400微克/分升。测定血清皮质醇与DHEA-S的比值也可能为肾上腺的功能和应激恢复能力提供一些建议。8

心率变异性

心跳并不是一个精确的规则节律,而是随着时间的推移不可预测地振荡,以响应交感神经和副交感神经调节平衡的动态变化。心率变异性是指心跳间隔时间的波动。124健康人在休息时,当副交感神经系统是主要的心律调节器时,心率变异性增加,但在压力期间,交感神经系统被强烈激活,心率变异性降低。与唾液α-淀粉酶一样,静息时的心率变异性提供了有关神经系统应激相关活动的信息。125心率变异性越大,反映出适应变化条件的能力越强。124

越来越多的证据表明,静息心率变异性是心脏和神经系统活动的一个有意义的反映。124,125低心率变异性与其他压力指标密切相关,是压力恢复能力低下、心脏病发作风险增加和总体死亡率增加的指标。125-128此外,压力管理策略如锻炼和正念练习可以改善心率变异性。128,129综合起来,证据表明,心率变异性可能有助于预测压力相关的身体和心理疾病的风险。 126,130

心率变异性在长时间(24小时)、短时间(5分钟)或超短时间(短于5分钟的)监测期间测量。目前,24小时数据集被视为“黄金标准”,似乎能更好地反映健康状况。关于短期和超短期心率变异性测量的意义、数据收集的理想时间、振荡频率以及性别、疾病状况和药物使用等个体因素对心率变异的影响,仍存在问题。124尽管如此,测量心率变异性的设备越来越商业化。

“肾上腺疲劳”问题

关于压力的讨论中经常出现的一个替代医学术语是“肾上腺疲劳”。虽然“肾上腺疲劳”在传统医学中不是公认的诊断,但通常归因于“肾上腺疲劳”的症状可能来自多因素的病理过程,包括其他系统,HPA轴。131,132

另一方面,Addison病,有时被称为“肾上腺功能不全”,是一种可能危及生命的疾病。Addison病通常是自身免疫性疾病的结果,但也可能是由于基因异常引起的。Addison病的后果比压力引起的后果严重得多,并且应由合格的医疗专业人员密切监测病情。133那些有兴趣了解更多Addison病的人可以通过回顾肾上腺疾病方案来做到这一点。


七、暂时缓解压力的药物

虽然没有专门用于治疗压力的药物,但在某些人中,压力是导致焦虑、抑郁、失眠或其他心理或精神疾病的主要因素,这些疾病可以用抗抑郁剂、镇静剂和抗焦虑药物治疗。此外,一些与压力有关的健康问题可能对皮质醇类似物氢化可的松的治疗有反应。

值得注意的是,在大多数情况下,这些药物并不是专门用来缓解压力的,只能暂时使用。在大多数患有慢性压力的人中,本方案后面描述的压力管理技术和饮食措施是减少压力相关症状和提高压力恢复力的最佳选择。

抗抑郁和抗焦虑药物

选择性5-羟色胺再摄取抑制剂(SSRIs)和5-羟色胺及去甲肾上腺素再摄取抑制剂(SNRIs)是广泛用于治疗抑郁和焦虑的抗抑郁药,也是压力相关情绪障碍患者的考虑因素。例如,SSRIs帕罗西汀(帕罗西汀)和舍曲林(佐洛特)以及SNRI文拉法辛(Effexor)在治疗社交焦虑症方面尤其有效。134案例研究表明,SNRI曲马多(Ultram)可以有效地减轻心理压力,可以根据需要服用而不是每天服用。135然而,这些药物可能导致依赖,在从焦虑或抑郁中获得缓解的成功率较低,并且与副作用有关,如恶心、性功能障碍、体重增加、失眠、头痛、疲劳和焦虑。136

丁螺环酮(Buspar)是一种抗焦虑药物,能增强5-HT1A受体的活性。丁螺环酮还可刺激HPA轴并提高儿茶酚胺水平。137动物研究结果表明,丁螺环酮可能在治疗压力相关的焦虑和抑郁138中发挥作用;然而,丁螺环酮可引起不良副作用,如不安、紧张、注意力不集中、睡眠困难、嗜睡,疲劳或虚弱。139

曲唑酮是一种非典型抗抑郁药。它的主要副作用是镇静,这导致它被用作睡眠辅助剂。136其他非FDA批准的使用曲扎酮的适应症包括焦虑症、惊恐障碍和创伤后压力障碍,尽管曲唑酮在这些情况下的疗效尚未确定。140,141

β受体阻滞剂

β受体阻滞剂是抑制儿茶酚胺受体(称为β肾上腺素能受体)的药物,从而抑制交感神经系统信号。142这些药物主要用于治疗高血压、心律失常、心绞痛和心力衰竭,是心脏病发作后维持的一部分。某些β受体阻滞剂也用于治疗青光眼、偏头痛、原发性震颤和甲亢的心脏症状。143,144

普萘洛尔(Inderal)是一种β受体阻滞剂,有时用于预防具有情境焦虑(如考试焦虑、怯场、表现焦虑和手术恐惧)的个体的急性压力。143,144对于这些用途,通常是间歇性和单剂量服用。它似乎不能有效治疗长期焦虑症,如应激性或广泛性焦虑症,但缺乏对照试验。142此外,有人担心长期使用普萘洛尔,即使是心血管适应症,也可能增加抑郁的风险。145

镇静药

苯二氮卓类药物是一类快速镇静药物,尽管批准的用途有限,但通常用于焦虑症患者,包括应激性焦虑和失眠。134,146,147这些药物能增强GABA的作用,GABA是一种神经递质,能抑制神经传导,可能抑制HPA轴的激活。苯二氮卓类147有安定、劳拉西泮和氯硝西泮。在一个社会心理应激的大鼠模型中,劳拉西泮和氯硝西泮都能减少中枢神经系统中与应激相关的炎症,并减少与应激引起的焦虑和抑郁相关的行为。148

苯二氮卓类药物与一系列问题有关,包括困惑和跌倒、认知障碍、戒断症状、依赖和滥用。它们的使用也增加了老年患者患肺炎的风险。此外,它们还与许多药物、酒精和其他物质相互作用。苯二氮卓类药物仅用于短期使用。147,149

用于失眠的非苯二氮卓类镇静剂包括佐匹克隆(Imovane)、艾司佐匹克隆(Lunesta)、唑吡坦(Ambien)和suvorexant(Belsomra)。虽然人们认为这些选择可能比苯二氮卓类药物更不易上瘾,但长期使用这些药物治疗失眠可能仍与认知障碍、跌倒、依赖和滥用、生活质量下降以及老年人肺炎风险增加有关。149-151

小剂量氢化可的松替代物

氢化可的松(Cortef)替代疗法通常是为Addison病患者保留的,但是一些非传统的医疗保健从业者为那些与慢性压力或慢性疲劳综合征相关的长期倦怠患者开小剂量氢化可的松,慢性压力以HPA轴活动不足为特征,随着时间的推移会导致HPA轴失调,在某些情况下,这反过来又会导致皮质醇分泌减少。在此基础上,综合从业人员有时会使用低剂量氢化可的松来抵消由于长期压力而可能引起的HPA轴功能障碍。 该策略通常保留给那些未通过其他干预措施(例如肾上腺)改善的人。氢化可的松的剂量通常为5至20毫克,可根据体重进行调整。

一些临床试验的结果表明,小剂量氢化可的松作为短期治疗药物可能是有益的。132例如,在一项交叉试验中(所有参与者都经历了积极治疗阶段和对照阶段),32名被诊断为慢性疲劳综合征的参与者,低剂量氢化可的松治疗28天比安慰剂显著减少疲劳。152然而,在100名慢性疲劳综合征患者的随机对照试验中,每天服用5毫克氢化可的松和50微克氟氢可的松(肾上腺激素醛固酮的类似物)6个月,在减少疲劳方面并不比安慰剂好。153这可能是由于长期服用氢化可的松会引起肾上腺抑制所致。154重要的是,氢化可的松的替代只能在有资格的临床医生的监督下进行,因为过量的可的松替代可能导致骨完整性受损和糖代谢受损等问题。


八、缓解压力的生活方式和行为技巧

毫无疑问,经历高压力及其对健康影响的人,通过减少他们在高压力环境下的暴露,会过得更好。然而,对许多人来说,家庭或工作上的压力似乎是不可避免的。在这种情况下,健康的饮食、锻炼和压力管理实践可以对压力反应正常化和预防压力相关疾病产生强烈的积极影响。

认知行为疗法

认知行为治疗(CBT)是指一组以患者为中心的技术,其重点是改变与情绪困扰和有害行为相关的思维模式。大量的临床研究表明,CBT是一种有效的控制压力和缓解焦虑的策略。155在2018年的一项临床试验中,100名患有慢性压力的受试者被分配参与为期12周的基于互联网的CBT干预或被列入候补名单。六个月后,接受干预者的感知压力和压力相关症状的测量值较低。156在另一项研究中发现,CBT在减轻慢性病儿童家长的压力和倦怠方面与正念减压(本节稍后介绍)具有相似的效果。157

最近的一项研究综述表明,CBT对治疗压力和焦虑相关的心理障碍具有中等有效性。158 CBT也被推荐为压力介导的慢性疼痛的治疗策略。159,160在一项对46名患有纤维肌痛(一种慢性疼痛状况)的妇女进行的研究中,为期六个月的CBT干预改善了对生活的控制感,增加了应对行为,减少了抑郁、疲惫和压力行为;这些益处在开始干预一年后得到维持和增强。161

一些受压力影响的人可能比其他人更容易受益:研究人员注意到,夜班工作、高倦怠分数和炎症标记物水平升高等因素可能会降低CBT的疗效。162

冥想和正念

冥想有助于调节压力反应,减少慢性炎症,维持健康的肠道微生物群,许多研究表明,冥想在治疗和预防各种健康疾病方面具有潜在的益处。4对患有创伤后压力障碍的退伍军人进行的研究表明,练习冥想不仅可以改善皮质醇释放的模式,还可以触发表观遗传学的变化,这也可能对应激反应产生积极影响。163,164

一项对45项研究的回顾发现,冥想可以降低皮质醇的分泌、血压、心率、甘油三酯和炎症标志物水平,这表明冥想有可能保护心血管健康。165美国心脏协会在2017年发表声明,承认冥想与戒烟、治疗高血压和高胆固醇一起,在降低心脏病风险方面可能发挥的作用。166

基于正念的减压是一个结构化的项目,包括冥想、身体觉知和温和的瑜伽,强调对当下的觉知。基于正念的压力减轻对各种心理和身体健康结果的益处已经被广泛报道。6例如,对医疗保健提供者和其他类型的工作者的研究的回顾表明,基于正念的干预可以增加幸福感,减少焦虑、抑郁和倦怠,并且可能会改善工作表现。167-170在一项针对超重和肥胖女性的对照试验中,为期四个月的正念计划减少了与压力相关的饮食行为,并防止了体重增加。171正念计划通常是亲自进行的,但基于在线正念的压力减少计划的有效性正受到越来越多的关注,其中在最近的临床试验中报告了积极的影响。172-174

锻炼

对许多人来说,压力降低了他们从事体育活动的欲望和动机,然而锻炼可以提高他们的抗压能力175,并且已经证明可以减轻焦虑和压力相关障碍患者的症状。176

锻炼似乎能刺激体内的抗炎和抗应激反应。177经常锻炼能提高身体适应应激的能力,并与更好地从疾病和手术中恢复有关。175锻炼能改善睡眠,178减少焦虑和抑郁,179,180神经系统和心血管系统的应激反应性较低。181一项对研究的回顾得出结论,每天大约50分钟的中等强度运动与较低或较高剂量的运动相比,对心理健康的益处最大;然而,久坐的时间削弱了一些体力活动对心理健康的积极影响。182临床证据还表明,力量训练可能有助于心理健康改善焦虑、抑郁和睡眠。183,184

运动可以减轻与压力相关的饮食行为:许多试验表明,即使是15分钟的快走也可以在短期内减少压力饮食。161此外,定期运动有助于预防或逆转慢性压力的代谢、炎症和神经后果,66,185,186许多研究支持目前世界卫生组织的建议,即每周至少进行150分钟的中等强度体力活动,作为减少各种原因死亡的有效方式。187

活动跟踪工具可能是有用的和有效的,将运动纳入压力管理方案。在2016年的一项初步研究中,35名久坐的超重参与者参加了一个为期12周的步行项目,他们使用计步器来计算每天的步数。成功达到每天10000步目标的30名参与者不仅体重减轻,腰围减小,而且在焦虑、抑郁、疲劳、困惑、愤怒和整体情绪困扰测试中的得分也比研究开始时低,在另一项试验中,通过使用步数活动跟踪器加目标设定干预来增加体力活动,减少了女性参与者的抑郁症状。191

社会支持

强大的社会支持网络可以缓冲对压力的感知,是维持终生压力弹性的关键因素之一。424,425作为弹性的一个特征,社会支持有助于防止压力对免疫功能和炎症的负面影响。425尽管个体的压力量和类型不同,研究一直表明,通过与朋友和家人接触以及加入宗教团体和其他团体,社会融合可以改善身心健康,延长寿命。426在从事压力职业的母亲中,建立社会网络可以改善心理健康和皮质醇水平。427在痴呆症患者的家庭护理者中,强大的社会支持与较低的负担感和较高的恢复力有关。428针对急救人员和重症监护室护士的研究表明,感知强大的社会支持与创伤后应激障碍症状的减轻有关。429-431在一项关于正式社会联系项目效果的研究中,那些提供社会支持的人与那些在压力期间接受支持的人在幸福感方面有相似的提高。432

宠物的减压特性

长期以来,研究人员一直对人类与同伴动物之间的关系以及这种关系对健康的影响感兴趣。总的来说,研究结果表明,养宠物与减少抑郁和孤独、更好的社会交往以及减少焦虑和压力有关。192

有几项研究指出,与非宠物主人相比,宠物主人的血压、胆固醇和甘油三酯水平较低,并且不太可能发生致命的心脏事件(心脏病发作和中风)。193-195虽然其中一些好处可能部分是由于与养狗相关的体力活动增加,养猫的人也有较低的心血管死亡风险,这使得研究人员提出养宠物也可能通过改善情绪和降低压力反应性来影响心血管健康。195-197

对狗辅助干预的研究表明,即使有一只不熟悉的狗出现,在固有的压力环境中,例如在牙科手术期间,也可以降低压力。198在实验室环境中,在另一项研究中,有宠物的参与者比没有宠物的参与者的基线血压和心率更低,心血管对生理和心理压力测试的反应也更低。此外,在压力测试中,宠物的出现会进一步降低压力反应性,而朋友的出现则没有影响,配偶的出现会增加压力反应性。200

维持性激素平衡

生理压力反应受到性激素(睾酮、雌激素和孕酮)的强烈影响,与性别有关的压力反应差异已被广泛记录。尽管这种关系很复杂,但压力诱导的HPA轴激活,一般来说,女性比男性更强。来自动物研究的证据表明,这可能是由于睾酮和雌激素对HPA轴敏感性的相反影响:雌激素增加HPA轴的反应性,而睾酮降低HPA轴的反应性。201,202此外,孕酮似乎抑制HPA轴的敏感性,并下调焦虑。203,204此外,虽然急性压力似乎会增加孕酮的分泌,但204慢性压力会抑制所有性激素的释放。202在另一项研究中,月经周期后半段孕酮水平升高与经前攻击性、易怒性和疲劳程度降低有关。205

绝经后妇女的雌激素和孕激素水平自然较低,激素治疗可影响压力反应的调节,并可增强压力时认知功能的某些方面。在一项研究中,15名长期使用激素替代疗法的绝经后妇女与15名从未使用激素疗法的类似妇女进行了比较。那些从未使用激素治疗的人被发现有不正常的唾液α-淀粉酶昼夜模式,而激素治疗使用者有正常的α-淀粉酶模式。此外,与激素治疗使用者相比,激素治疗非使用者对运动的反应唾液α-淀粉酶浓度上升较少。这表明长期激素治疗可能有助于维持交感神经系统的正常张力。206另一方面,另一项试验发现,与接受安慰剂的妇女相比,使用雌二醇治疗的绝经后妇女在暴露于身体压力后的皮质醇反应降低,工作记忆减少较少。207

在一项对94名绝经后妇女进行的初步研究中,由于照顾痴呆症患者的家庭成员而处于慢性压力下,激素治疗与更好的心理社会功能相关:与未使用激素治疗的妇女相比,使用激素治疗的妇女与支持团队成员的敌意和负面互动较少;同时使用雌二醇和孕酮的患者获益最大。208

孕酮治疗可以帮助围绝经期妇女的症状,包括潮热,乳房疼痛和睡眠问题。209,210因为这些症状可能是压力的来源,在围绝经期和绝经后妇女,孕酮治疗可能有抗压力的好处。此外,动物研究表明黄体酮可以保护大脑免受有害的压力炎症的影响

综上所述,这些发现表明,在一生中保持平衡的性激素水平可能对调节压力反应和提高恢复力很重要。可能存在激素失衡的男性和女性应该回顾男性激素恢复和女性激素恢复方案。

更年期相关压力的非激素选择

尽管有令人信服的证据表明激素替代疗法可能有助于缓解与更年期和老年妇女激素失衡有关的压力症状,但激素替代疗法并不吸引所有人。一种从西伯利亚大黄中提取的植物雌激素制剂ERR731已经被证明可以缓解更年期相关的焦虑并改善总体健康状况。436,437

在一项多中心、前瞻性、随机、安慰剂对照试验中,109名围绝经期妇女服用ERR731或安慰剂12周。与服用安慰剂的女性相比,服用ERR731的女性焦虑感显著降低。此外,服用ERR731的女性比服用安慰剂的女性更经常报告总体上的改善情况。436


九、食物和压力-饮食如何影响压力?

众所周知,压力会引发饮食行为的改变,通常会增加对不健康的“舒适”食物(如高糖和高脂肪食物)的食欲。212原因之一可能是压力会改变食欲调节激素、ghrelin和leptin的水平,产生更多的饥饿信号。213尽管不是每个人都在压力下吃得更多(大约40%的人吃得更多,40%的人吃得更少,20%的人在压力下吃同样数量的卡路里),一直以来,人们都观察到压力引起的对高糖食物偏好的增加,部分原因可能是由于糖对压力反应的抑制作用。214-217使问题更加复杂的是,压力似乎增加了对饮食相关代谢紊乱(如腹部肥胖和胰岛素抵抗)的易感性。218

对抗压力引起的食欲变化和食物渴求是一项挑战;然而,在压力时期,健康饮食可能更为重要。健康的饮食习惯有助于确保足够的维生素、矿物质、蛋白质、复合碳水化合物、消炎脂肪、纤维和植物化学物质的摄入,这些都是对抗慢性压力对健康的负面影响和中断压力循环及压力相关行为所需的。219,220

摄入更多的水果和蔬菜

增加水果和蔬菜的摄入量有助于对抗压力。一项针对年轻人的研究表明,连续两周每天增加两份水果和蔬菜的摄入量,可以增强心理健康、活力、活力和动力。221地中海式饮食,强调橄榄油、全谷物、水果、蔬菜、鱼、坚果和种子,可以改善应激反应与更好地调节HPA轴活性有关。这种饮食模式还可以通过减少全身炎症和许多慢性健康问题的风险来减轻压力的影响。222-224

有规律地吃早餐

吃早餐可能有助于增强抗压能力。与不吃早餐相比,在一项包含800多名护士的研究中,习惯性吃早餐与较低的感知压力、更好的认知功能、较少的工伤和事故有关。225在另一项针对65名女性参与者的研究中,习惯性不吃早餐减弱了皮质醇每天的变化,与习惯性早餐者相比,总皮质醇分泌增加,血压升高,这表明早餐对于维持HPA轴的正常昼夜节律调节可能很重要。226

尽量减少咖啡因和酒精的摄入

咖啡因对那些受压力相关疲劳影响的人来说似乎很有吸引力,但它的影响可能会加重易感人群的焦虑和睡眠不良等症状。227,228咖啡因刺激交感神经系统,并通过这种方式激活应激反应。229即使每天食用,它的摄入也会提高皮质醇水平,睡眠质量研究发现,咖啡因可以增加皮质醇对精神压力的反应。230,231咖啡因还可以延长身体压力对心率和血压的影响。232在一项研究中,习惯性饮用咖啡与精神压力引起的心率和血管炎症的更大增加有关。233另一方面,喝咖啡似乎可以促进健康的新陈代谢,并可以预防2型糖尿病、肝癌和认知能力下降。234虽然敏感的人在压力时期可以更好地消除咖啡因带来的影响,但适度摄入对其他人来说可能是合理的。227

在压力时期,酒精经常被用作松弛药235,236;然而,过量摄入会提高皮质醇水平,长期使用会导致HPA轴信号失调,并破坏压力反应的正常功能。237-239患有压力相关失眠的人经常将酒精作为自我药物治疗的一种形式,但是因为酒精会侵蚀睡眠质量和时间,它实际上可能会加剧睡眠困难。240此外,有早期生活压力史的人和经历过强烈生活压力的人更容易养成有问题的饮酒习惯。239,241因此,避免与压力有关的酒精使用尤为重要。


十、缓解压力的自然和综合干预措施

各种自然的综合干预措施已被证明有助于平衡HPA轴功能,抵消慢性压力的不利影响。

复合维生素和复合维生素B

维生素B缺乏与神经精神疾病有关,如抑郁症、阿尔茨海默病、精神分裂症和其他类型的精神病和痴呆症,健康的神经系统功能需要足量的所有维生素B。242,243

多种维生素降低感知压力和疲劳的能力已在许多试验中得到证实。244-248在一项对60名成年工作人员进行的随机对照试验中,与接受安慰剂的人相比,每天接受高剂量复合维生素B治疗12周的人的压力、困惑和抑郁情绪水平较低。249 一项对研究的回顾得出结论,多种维生素,特别是复合维生素B补充剂,可以有效地降低健康人的感知压力,减轻轻微的精神症状,改善日常情绪。250

维生素B也可能支持正常的HPA轴功能。在一项有138名受试者参加的安慰剂对照试验中,16周内补充含有B族维生素的复合维生素可增加皮质醇的觉醒反应。皮质醇唤醒反应,在醒来后30分钟左右出现,通常会导致一天中皮质醇水平最高,被认为是健康HPA轴的标志,并与一天中其他时间较低的痛苦水平有关。251另一项随机对照交叉试验研究了240名经历强烈身体压力的中国军人服用多种维生素补充剂一周的治疗效果。复合维生素能更好地恢复正常的HPA轴功能和改善心理症状。252

维生素C(抗坏血酸)

肾上腺体内维生素C的浓度最高。253除了众所周知的自由基清除剂功能外,维生素C是参与应激反应的儿茶酚胺类神经激素合成的辅助因子,可能有助于调节中枢神经系统的活动。253-255在压力或感染期间,血液和白细胞中的维生素C含量会迅速下降256,而抑郁症和焦虑症的症状与维生素C的摄入量少和循环水平低有关。254

在一项对照临床试验中,患有压力引起的焦虑和抑郁的患者维生素C以及维生素E和A的水平低于健康受试者,并且添加了这些营养素(每天1,000 mg维生素C,每天800 mg 与单独使用抗抑郁药相比,每天服用维生素E和每天服用600毫克维生素A)可以使焦虑和抑郁症状的减轻很多。257另一项对照试验发现,每天补充500毫克的维生素C可以降低健康高中生的焦虑水平和平均心率。此外,一项研究回顾表明,高剂量的维生素C可以减少焦虑和缓解压力引起的血压升高。259

Omega-3脂肪酸

Omega -3脂肪酸(主要是来自鱼油的EPA[二十碳五烯酸]和DHA[二十二碳六烯酸])可能有助于预防和治疗压力、焦虑和抑郁。260-262血液中EPA和DHA的低水平与压力的几个生物学指标相关:炎症标记物升高、神经系统信号传导失调,和HPA轴高反应性。263,264相反,主要通过食用动物脂肪和加工过的植物油获得的omega-6脂肪酸会促进炎症,从而诱导压力信号并导致压力相关疾病。261

在一项针对高甘油三酯水平参与者的随机对照试验中,服用3400毫克EPA和DHA的联合治疗8周,心率变异性增加,表明压力相关的神经系统信号较低;然而,每天850毫克的低剂量没有效果。265另一个对照试验发现,在一项住院治疗计划中,每天服用60毫克EPA和252毫克DHA治疗三周,可以改善酒精中毒者的压力和焦虑感,降低皮质醇水平。266抑郁症患者试验的证据表明,omega-3脂肪酸可以改善HPA多动症,减轻症状,并可能提高抗抑郁药治疗的反应性。264,267

l-茶氨酸

茶氨酸是茶叶中的一种氨基酸,具有抗应激作用。许多研究发现,茶和茶氨酸可以降低人们对压力的感知和压力反应的生理指标,包括血压、心率、皮质醇水平和大脑活动模式。268在一项包括20名药学专业学生的试验中,每天两次服用200 mg茶氨酸,持续一周,比安慰剂更能降低早晨唾液α-淀粉酶水平。此外,服用L-茶氨酸的受试者的主观压力明显低于服用安慰剂的受试者。269

L-茶氨酸的短期效应在另一项随机对照试验中得到证实,试验对象为36名18至40岁的健康受试者:单次200 mg剂量的茶氨酸在给药1小时后降低了主观应激,在给药3小时后降低了皮质醇对认知应激源的反应。此外,在经历焦虑倾向测试得分较高的一部分参与者中,茶氨酸增加了与放松相关的脑波活动。270

日本研究人员进行的一系列小型试验发现,补充L-茶氨酸可防止在实验室进行压力诱发算术测试时心率升高。服用L-茶氨酸的人,唾液免疫球蛋白A(s-IgA)水平也会因压力任务而降低。研究人员得出结论,服用L-茶氨酸的受试者心率和s-IgA的降低可能归因于交感神经系统活动的减弱。438

茶氨酸也被证明可以对抗咖啡因的应激诱导作用,提高注意力的集中度,271一项为期两个月的临床试验指出,茶氨酸与维生素/矿物质/草药补充剂联合使用,可以降低老年受试者的感知压力得分,改善认知功能。272

磷脂酰丝氨酸

磷脂磷脂酰丝氨酸存在于细胞膜中,有助于促进健康的细胞通讯。它调节组织对炎症的反应,并可减少氧化应激。273多项研究表明,磷脂酰丝氨酸可平衡HPA轴信号,并可限制肾上腺过度激活的负面后果。

在一项对75名健康男性志愿者进行的试验中,补充400毫克的磷脂酰丝氨酸及其前体磷脂酸42天,减少了一部分报告慢性压力水平高的男性对急性应激的HPA轴反应。274在其他临床研究中,同样的组合也可以抑制精神压力的应激反应,每天单独服用275毫克和300毫克的磷脂酰丝氨酸,可以降低易产生焦虑、担忧、焦虑等负面情绪的健康年轻人的感知压力,改善情绪,此外,还发现磷脂酰丝氨酸可降低男性的皮质醇水平,降低皮质醇对急性运动的反应,这种作用可能有助于防止过度训练的有害后果,如表现下降、受伤、免疫抑制和心理健康状况恶化。277

姜黄素

姜黄素是从姜黄根中提取的一种色素,其特征是黄橙色。作为一种多酚,姜黄素具有很强的自由基猝灭和抗炎作用,历史上曾被用于治疗一系列炎症疾病,包括肌肉骨骼问题、神经系统疾病、心脏病和糖尿病。439大量临床研究表明姜黄素有可能降低慢性炎症的影响,此外,临床前证据表明姜黄素的抗压力作用可能与其减少神经炎症和保持神经可塑性的能力有关。445-447

多个随机对照试验和三个荟萃分析表明,姜黄素可以减轻抑郁症患者的抑郁和焦虑症状。448-450一项针对60名患有职业压力相关焦虑症的参与者的临床试验比较了每天剂量1,000 mg的高吸收姜黄素加葫芦巴与标准剂量姜黄素或安慰剂的组合。 30天后,与服用普通姜黄素或安慰剂的受试者相比,服用姜黄素/葫芦巴组合的受试者在压力,焦虑和疲劳方面的减轻更大,生活质量也得到更大的改善。451在另一项80例安慰剂对照试验中患有糖尿病性神经病变的参与者,与安慰剂相比,每天服用80毫克另一种高度可吸收形式的姜黄素,持续8周,导致抑郁和焦虑症状评分降低。452在患有严重抑郁症的患者中,接受1,500毫克姜黄素的患者与接受安慰剂的患者相比,每天接受治疗12周的患者抑郁症的改善更大。此外,在试验结束后的四个星期内仍可测得这种益处。453在耐力训练过程中,补充姜黄素也能使运动员更好地降低感知压力水平454

L-色氨酸

色氨酸是神经递质血清素的前体氨基酸。5-羟色胺与应激反应有着复杂的关系。278压力诱导的炎症似乎会导致色氨酸的过度分解,这可能会减少5-羟色胺的生成,增加抑郁的风险279;此外,色氨酸缺失已被证明会增加压力敏感性。280针对健康成年人的研究表明,每天补充800至2800毫克色氨酸,可降低皮质醇对压力的反应,缓解压力相关的负面情绪,并防止某些人出现压力性进食。281-283在一项随机对照试验中,富含色氨酸的水解蛋白补充剂增加了积极的情绪,降低了皮质醇的释放,以应对急性压力。284

生物活性乳肽

摄入牛奶后,牛奶蛋白质被酶分解成肽(缩短的氨基酸链)。一些产生的肽可以被完整地吸收并发挥生物活性。285例如,α-乳清蛋白是一种具有高色氨酸含量的生物活性乳肽,已被发现可支持健康的神经功能、改善情绪和促进睡眠。286一种经酶处理的乳蛋白,酪蛋白,在动物研究中也证明了抗压力和放松的特性,并且似乎通过GABA受体增加信号传导而起作用,GABA是一种神经递质,通常用作抑制神经系统的活动。287-289

一项随机、对照、交叉试验包括63名患有焦虑、睡眠问题和疲劳等压力相关症状的女性。每天150毫克α-S1酪蛋白水解物(一种生物活性乳肽)治疗30天,在缓解症状方面比安慰剂更有效。290在健康志愿者中,发现200毫克剂量的α-S1酪蛋白水解物可以缓解实验压力引起的血压、心率和皮质醇释放的增加。291

益生菌和益生元

肠道微生物群、神经系统和HPA轴密切相关。益生菌和益生元(支持有益细菌菌落生长的不可消化的膳食碳水化合物)可以改善肠道细菌的平衡,越来越多的证据表明,益生菌和益生元有可能对压力反应产生积极影响。35,37,260研究表明,益生菌可以降低压力反应和焦虑,改善情绪、记忆力和认知能力,这使得一些研究人员称益生菌为具有这些作用的心理生物素。292

由干酪乳杆菌菌株Shirota制成的发酵乳制品已在多个试验中被发现,可抑制压力时皮质醇升高,并减少健康医学生的压力相关健康问题,如抑郁或焦虑情绪、消化紊乱和感冒症状。293-295在一项随机对照试验中,10天每天补充100亿菌落(CFU)的植物乳杆菌299v可降低即将接受考试的学生的唾液皮质醇水平。296在其他对照试验中,服用瑞士乳杆菌R0052和长双歧杆菌R0175的联合制剂,剂量为每天30亿CFU,在30天内,健康志愿者的感知压力量表得分和尿皮质醇水平降低297,并在四周内每天补充10亿CFU的长双歧杆菌1714,抑制了皮质醇升高和与急性压力源相关的主观焦虑。298

益生元在临床研究中也显示出积极的作用:在45名健康成年人的试验中,服用5.5克含有低聚半乳糖的益生元补充剂三周,可降低清晨皮质醇水平,使积极和消极情绪刺激的处理更加平衡。299

褪黑素

褪黑激素是从大脑底部的松果体释放出来的,它与睡眠周期有关。褪黑素在包括HPA轴在内的身体系统的昼夜节律调节中起着核心作用。300压力会降低褪黑素水平,并破坏身体的生物节律。301大脑内部时钟的慢性破坏,如轮班工作或失眠,会损害身心健康。302,303

补充褪黑素可以改善睡眠的时间和质量,帮助恢复正常的昼夜节律过程,304,305这可能会减少压力,防止压力相关的健康恶化。306在一项研究中,在一组老年女性志愿者中,晚上服用2毫克褪黑素6个月,改善了睡眠,提高了DHEA-S水平。307

脱氢表雄酮

脱氢表雄酮(DHEA)是一种肾上腺激素,与皮质醇一样,在急性应激时分泌,但是,慢性压力与低水平DHEA有关。8压力对DHEA的影响可能是压力与健康状况不佳和加速衰老的因素之一。121低DHEA-S水平与骨质疏松症、认知能力下降和痴呆症、心血管疾病、心境障碍等疾病有关,123临床前和临床研究的结果表明,DHEA替代疗法可能在保护老化的骨骼和血管系统方面发挥作用,并可能有助于治疗抑郁症和性功能障碍。122,123

在一项随机、安慰剂对照、交叉试验中,年龄在40至70岁之间的13名男性和17名女性参加了这项试验,每天服用50毫克DHEA治疗6个月后,他们的身心健康状况得到了显著改善。在这项研究中,受试者表现出更好的处理压力的能力,改善了情绪,并且总体上放松了。308在另一项研究中,24名健康的年轻男性连续7天服用高剂量DHEA(150毫克,每天两次)。受试者的情绪有所改善,DHEA治疗导致夜间皮质醇水平下降。309

DHEA的补充剂量通常为女性每天10-25毫克,男性每天25-75毫克,但应基于DHEA-S的血液水平。有关更多信息,请的DHEA恢复治疗方案。

荔枝和绿茶

一种将荔枝果实中的多酚和绿茶中的儿茶素结合起来的补充剂,称为低聚醇,被发现具有很强的自由基猝灭和炎症抑制能力。433它也可能具有压力调节作用。一项针对19名健康久坐男性的初步研究,将每天100毫克低聚醇与安慰剂进行了为期四周的比较。在研究过程中,接受寡醇治疗的患者皮质醇和某些炎症标志物水平降低。此外,与安慰剂相比,低聚醇治疗的男性对运动的皮质醇反应较低。434在一项对13名健康男性服用低聚醇的急性效应的研究中,单次100毫克剂量可降低皮质醇以及由身体压力引起的炎症标记物的升高。435

调理素

调理草本植物有多方面的有益作用,支持身体对压力反应的内在弹性。它们通过调节生物网络来维持体内平衡。例如,调理素可以提高能量水平,但也支持良好的睡眠。使用调理素的一些典型原因包括缓解疲劳、改善认知功能和情绪以及支持免疫系统。310-312

木兰和黄柏。厚朴是一种重要的中草药植物。其活性成分厚朴酚与和厚朴酚在临床前和临床试验中被发现具有多种有益作用,包括减轻压力。313在暴露于慢性压力的啮齿类动物中,厚朴酚和和厚朴酚以及它们的组合都被发现能使血清素和HPA轴活性正常化,增加a水平脑生长因子(脑源性神经营养因子,或BDNF),减少神经炎症和脑氧化应激,预防抑郁行为。314-317

木兰和黄柏(黄柏,又名黄柏,常用于中药)的组合也被用以研究抗压力作用。在一项对照临床试验中,56名中等压力水平的健康受试者接受了补充250毫克的木兰加黄柏或安慰剂,每天两次,持续四周。参与者接受了三次唾液皮质醇测试(早上、中午和晚上),并在试验开始和结束时回答了情绪问卷。与安慰剂组相比,接受补充剂组的总皮质醇暴露量更低,情绪得分更好。318

研究了同一种复合补充剂对压力引起的食欲和体重增加的影响。在一项对照试验中,白玉兰加黄柏,剂量为250毫克,每天三次,连续六周,与安慰剂相比,超重但其他方面健康的绝经前妇女体重增加减少,这些妇女报告有压力饮食,焦虑水平高于平均水平。319在另一项类似设计的试验中,木兰加黄柏可减轻暂时性焦虑,但不影响长期抑郁或焦虑、食欲、睡眠或唾液皮质醇和淀粉酶水平。320

圣罗勒。圣罗勒(罗勒圣殿,也被称为图尔西罗勒)是一种来自于阿育吠陀传统的适应原草药。在印度教的灵性中,圣罗勒被认为是一种神圣的植物,是图尔西女神的化身。321许多临床和临床前研究证明,圣罗勒具有抗压力的潜力,它可以改善情绪和认知,使新陈代谢正常化,调节免疫功能,减少氧化应激,并通过支持解毒来防止各种组织中的毒性损伤。321,322

在一项有40名参与者参加的随机对照试验中,与安慰剂相比,每天服用300毫克罗勒提取物30天,焦虑症状减轻,认知测试得分提高。323另一项随机对照试验的结果,其中150名参与者每天服用1200毫克罗勒或安慰剂,这表明,圣罗勒降低了焦虑、疲劳、睡眠困难和性功能障碍等与压力相关的症状。324一项试验中,35名焦虑症患者每天服用500毫克圣罗勒两次,结果发现,治疗可减少焦虑、压力和抑郁的症状。325

Ashwagandha。Ashwagandha(Withania somnifera)是阿育吠陀草药药房中的另一种重要草药,在阿育吠陀草药药房中,它被用作一般补药和壮阳药。326大量临床前研究表明,Ashwagandha可防止氧化损伤,支持正常线粒体活动,调节中枢神经系统信号,并有助于免疫调节,提示它可能有助于治疗慢性应激相关、炎症、代谢、心血管和神经退行性疾病。327-329

一些临床试验进一步表明,ashwagandha能有效缓解压力和焦虑。330例如,在一项有64名参与者参加的试验中,在治疗60天后,每天两次服用300毫克ashwagandha提取物比安慰剂更能有效地降低感知压力得分和降低血皮质醇水平。331另一项试验指出,ashwagandha对慢性压力患者的体重管理可能有好处。52名慢性压力的参与者每天两次服用300毫克ashwagandha,或服用安慰剂,为期8周;与服用安慰剂的参与者相比,服用ashwagandha的参与者在感知压力和血清皮质醇水平方面有更大的降低,对食物的渴求和饮食行为方面有更多的改善,体重也有更大的减轻。332

巴科帕。Bacopa(Bacopa monnieri)历来被用于阿育吠陀医学中,以支持健康的认知功能。333许多动物研究证明了它的适应原潜力,注意到它能够使应激激素水平和神经递质平衡正常化,334减少氧化应激,335防止神经退化,此外,在慢性应激的啮齿类动物模型中,bacopa和一种活性成分(bacopaside I)被发现可以减少抑郁行为,使HPA轴功能正常化,减少脑氧化应激,防止BDNF下降和其他变化,在另一个实验动物模型中,Bacopa也被发现能增加压力恢复力和动物寿命。

在对17名健康成年人进行的初步试验中,一种单剂量服用320毫克和640毫克的标准化巴科帕提取物,在一至两小时后进行多任务智力测试时,提高了认知能力,同时降低了皮质醇水平,表明其认知益处的一部分可能与减压作用有关。344在一项针对54名老年受试者的随机对照试验中,与安慰剂相比,每天服用300毫克bacopa 12周,可改善认知能力,降低抑郁和焦虑评分,降低心率。345

柠檬香膏。柠檬香膏(Melissa officinalis)是薄荷科的一种植物,在草药中用作放松和振奋神经系统的补品。346,347在食物或饮料中食用,发现柠檬香膏通常能改善健康年轻人的情绪和认知能力。348在暴露于实验压力的健康受试者中,个体剂量的柠檬香膏润唇膏具有急性抗压力和认知增强作用,并增加了自我报告的镇静和警觉性。349

在20名患有轻度至中度焦虑和失眠的受试者中进行的一项试点试验中,用300毫克柠檬香膏提取物治疗15天,每天两次,19名受试者(95%)的症状得到改善。此外,14名受试者的焦虑完全缓解,17名受试者的失眠症状缓解,14名受试者的焦虑和失眠症状均得到缓解。350在一项安慰剂对照临床试验中,对80名稳定型心绞痛患者进行了为期8周的每日3克柠檬香膏治疗,以减轻焦虑、抑郁和压力,改善睡眠。351在动物研究中,柠檬香膏可以减少压力引起的肠易激综合征症状。352

藏红花。藏红花(番红花)是一种黄色香料,因其颜色和味道而备受推崇。由于其镇静、适应性和其他特性,它在草药中的应用也有很长的历史。几项临床试验表明,藏红花有助于治疗轻中度抑郁症。353,354藏红花及其活性成分番红花苷在动物实验中也显示出抗压力和抗焦虑的作用,临床前的证据表明,它可能通过调节HPA轴的反应性发挥其部分作用。355-358此外,藏红花中的另一种活性化合物西红花酸被发现可以预防压力诱导的大鼠抑郁行为。359

在一项随机对照试验中,无抑郁但情绪低落的受试者在接受每天28毫克藏红花提取物治疗四周后,其情绪改善程度以及压力和焦虑症状的减轻程度均大于接受安慰剂的受试者。360

人参。人参是一组类似植物的共同名称,包括亚洲人参(人参)、西洋参(西洋参)和中国人参(三七)。这些植物都含有被称为人参皂甙的活性化合物。人参及其独特的人参皂甙因其对疾病预防和整体健康的作用而被广泛研究。361这种草药已被用于增强生命力和寿命数千年,大量研究表明它具有广泛的作用,如免疫调节、抗炎、抗癌,自由基清除、神经保护和心脏保护。362-365关于压力生理学,发现发酵的人参提取物可减少氧化应激和运动压力时的HPA轴信号。366

虽然与人参属植物无关,但西伯利亚人参是另一种流行的适应原草本植物。它含有一种叫做榄香苷的活性化合物,并具有一系列抗压力的特性。367

红景天。红景天(Rhodiola rosea,也称为玫瑰根或金根)是一种适应性草本植物,生长在北极地区,在世界各地用于增强体力和精神耐力,缓解压力。368红景天似乎可以调节HPA轴功能,减少氧化应激,调节免疫活动。369,370

对有慢性疲劳症状、精疲力竭和轻度焦虑的患者进行的初步试验发现,每天400毫克红景天提取物与改善能量水平、情绪、睡眠、认知功能和总体幸福感有关。371-373红景天也被发现有助于压力诱发抑郁症的患者。374这种效果可能部分原因在于它促进了大脑中的新连接。375

印度醋栗。印度醋栗(amla)是一种适应原,用于阿育吠陀医学中,以恢复力量和良好的健康。376它的一些活性成分已显示出强大的氧化应激降低能力。377在12名健康志愿者的初步试验中,500毫克标准化的amla提取物,每天两次,持续14天,缓解了急性压力引起的动脉僵硬增加和心脏血流量减少。378对动物的研究表明,amla可以减少大脑氧化应激,防止慢性压力对睾丸组织的损伤,提高一般的压力恢复能力,延长寿命。379-381

五味子。五味子(五味子)用于治疗抑郁症、焦虑症和失眠,以及与疲劳和虚弱有关的各种健康问题已有数百年的历史。382,383五味子及其活性成分还具有保肝、抗炎、免疫调节、抗增殖、,以及认知增强效应。五味子也有望成为心脏和神经保护剂。382-384动物研究结果表明,五味子可能有助于调节HPA轴的活动,减轻压力的负面影响。385-387

虫草。冬虫夏草(Ophiocordyceps sinensis)是一种真菌/昆虫复合物,用于中医治疗疲劳,促进健康、长寿和体力活动。388,389许多来自冬虫夏草的活性化合物已经被鉴定出来,研究表明它们具有抗炎、免疫调节和氧化应激减轻作用。390此外,临床前研究表明,冬虫夏草具有潜在的抗衰老、抗疲劳、神经保护和壮阳剂的作用。389在慢性应激动物模型中,补充冬虫夏草可缓解不可预测和反复轻度压力诱导的抑郁样行为。此外,冬虫夏草治疗减少了一些炎症标记物和BDNF的上调表达。391初步的临床证据表明,冬虫夏草可以提高运动成绩,抑制运动引起的皮质醇释放增加,这可能有助于防止过度训练的有害影响。392


本文提出了许多问题,这些问题可能会随着新数据的出现而发生变化。 我们建议的营养或治疗方案均不用于确保治愈或预防任何疾病。Piping Rock健康研究院没有对参考资料中包含的数据进行独立验证,并明确声明对文献中的任何错误不承担任何责任。


十一、参考文献

1.Dhabhar FS. Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res. May 2014;58(2-3):193-210.

2.Duric V, Clayton S, Leong ML, Yuan LL. Comorbidity Factors and Brain Mechanisms Linking Chronic Stress and Systemic Illness. Neural Plast. 2016;2016:5460732.

3.Herman JP, McKlveen JM, Ghosal S, et al. Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response. Compr Physiol. Mar 15 2016;6(2):603-621.

4.Househam AM, Peterson CT, Mills PJ, Chopra D. The Effects of Stress and Meditation on the Immune System, Human Microbiota, and Epigenetics. Adv Mind Body Med. Fall 2017;31(4):10-25.

5.McEwen BS. In pursuit of resilience: stress, epigenetics, and brain plasticity. Ann N Y Acad Sci. Jun 2016;1373(1):56-64.

6.Worthen M, Cash E. Stress Management. StatPearls. Treasure Island (FL): StatPearls Publishing LLC.; 2018.

7.Dantzer B, Fletcher QE, Boonstra R, Sheriff MJ. Measures of physiological stress: a transparent or opaque window into the status, management and conservation of species Conservation Physiology. 2014;2(1):cou023-cou023.

8.Kamin HS, Kertes DA. Cortisol and DHEA in development and psychopathology. Horm Behav. Mar 2017;89:69-85.

9.Tsigos C, Kyrou I, Kassi E, Chrousos GP. Tsigos C, Kyrou I, Kassi E, et al. Stress, Endocrine Physiology and Pathophysiology. [Updated 2016 Mar 10]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278995/. Accessed 10/26/2018. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2016.

10.Harrell CS, Gillespie CF, Neigh GN. Energetic stress: The reciprocal relationship between energy availability and the stress response. Physiol Behav. Nov 1 2016;166:43-55.

11.Rao R. Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development. J Clin Med. Sep 2015;4(9):1729-1740.

12.Wood SK, Valentino RJ. The brain norepinephrine system, stress and cardiovascular vulnerability. Neurosci Biobehav Rev. Mar 2017;74(Pt B):393-400.

13.Kritikou I, Basta M, Vgontzas AN, et al. Sleep apnoea and the hypothalamic-pituitary-adrenal axis in men and women: effects of continuous positive airway pressure. Eur Respir J. Feb 2016;47(2):531-540.

14.Shin W, Jen R, Li Y, Malhotra A. Tailored treatment strategies for obstructive sleep apnea. Respir Investig. Jan 2016;54(1):2-7.

15.Spiers JG, Chen HJ, Sernia C, Lavidis NA. Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress. Front Neurosci. 2014;8:456.

16.Gadek-Michalska A, Tadeusz J, Rachwalska P, Bugajski J. Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems. Pharmacol Rep. 2013;65(6):1655-1662.

17.Spencer RL, Deak T. A users guide to HPA axis research. Physiol Behav. Sep 1 2017;178:43-65.

18.McEwen BS, Nasca C, Gray JD. Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex. Neuropsychopharmacology. Jan 2016;41(1):3-23.

19.Charoensri S, Chailurkit L, Muntham D, Bunnag P. Serum dehydroepiandrosterone sulfate in assessing the integrity of the hypothalamic-pituitary-adrenal axis. J Clin Transl Endocrinol. Mar 2017;7:42-46.

20.JCCL. Jo Cox Commission of Loneliness: A Call to Action. Available at https://www.jocoxloneliness.org/pdf/a_call_to_action.pdf. Published 2017. Accessed 11/04/2018. 2017.

21.Pimlott N. The ministry of loneliness. Can Fam Physician. Mar 2018;64(3):166.

22.Leigh-Hunt N, Bagguley D, Bash K, et al. An overview of systematic reviews on the public health consequences of social isolation and loneliness. Public Health. Nov 2017;152:157-171.

23.Courtin E, Knapp M. Social isolation, loneliness and health in old age: a scoping review. Health Soc Care Community. May 2017;25(3):799-812.

24.Brown EG, Gallagher S, Creaven AM. Loneliness and acute stress reactivity: A systematic review of psychophysiological studies. Psychophysiology. May 2018;55(5):e13031.

25.Dumbell R, Matveeva O, Oster H. Circadian Clocks, Stress, and Immunity. Front Endocrinol (Lausanne). 2016;7:37.

26.Liyanarachchi K, Ross R, Debono M. Human studies on hypothalamo-pituitary-adrenal (HPA) axis. Best Pract Res Clin Endocrinol Metab. Oct 2017;31(5):459-473.

27.Strohmaier S, Devore EE, Zhang Y, Schernhammer ES. A Review of Data of Findings on Night Shift Work and the Development of DM and CVD Events: a Synthesis of the Proposed Molecular Mechanisms. Curr Diab Rep. Oct 20 2018;18(12):132.

28.De Nobrega AK, Lyons LC. Aging and the clock: Perspective from flies to humans. Eur J Neurosci. Sep 30 2018.

29.Helfrich-Forster C. Interactions between psychosocial stress and the circadian endogenous clock. Psych J. Dec 2017;6(4):277-289.

30.Ouakinin SRS, Barreira DP, Gois CJ. Depression and Obesity: Integrating the Role of Stress, Neuroendocrine Dysfunction and Inflammatory Pathways. Front Endocrinol (Lausanne). 2018;9:431.

31.Bekhbat M, Rowson SA, Neigh GN. Checks and balances: The glucocorticoid receptor and NFkB in good times and bad. Front Neuroendocrinol. Jul 2017;46:15-31.

32.Silverman MN, Sternberg EM. Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Ann N Y Acad Sci. Jul 2012;1261:55-63.

33.Nezi M, Mastorakos G, Mouslech Z. Corticotropin Releasing Hormone And The Immune/Inflammatory Response. [Updated 2015 Jul 30]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279017/. In: De Groot LJ, Chrousos G, Dungan K, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2015.

34.Meyer T, Wirtz PH. Mechanisms of Mitochondrial Redox Signaling in Psychosocial Stress-Responsive Systems: New Insights into an Old Story. Antioxid Redox Signal. Mar 20 2018;28(9):760-772.

35.Rea K, Dinan TG, Cryan JF. The microbiome: A key regulator of stress and neuroinflammation. Neurobiol Stress. Oct 2016;4:23-33.

36.Lerner A, Neidhofer S, Matthias T. The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologists. Microorganisms. Oct 12 2017;5(4).

37.Farzi A, Frohlich EE, Holzer P. Gut Microbiota and the Neuroendocrine System. Neurotherapeutics. Jan 2018;15(1):5-22.

38.Sudo N. Microbiome, HPA axis and production of endocrine hormones in the gut. Adv Exp Med Biol. 2014;817:177-194.

39.van Bodegom M, Homberg JR, Henckens M. Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure. Front Cell Neurosci. 2017;11:87.

40.Reul JM, Collins A, Saliba RS, et al. Glucocorticoids, epigenetic control and stress resilience. Neurobiol Stress. Jan 2015;1:44-59.

41.Constantinof A, Moisiadis VG, Matthews SG. Programming of stress pathways: A transgenerational perspective. J Steroid Biochem Mol Biol. Jun 2016;160:175-180.

42.Dirven BCJ, Homberg JR, Kozicz T, Henckens M. Epigenetic programming of the neuroendocrine stress response by adult life stress. J Mol Endocrinol. Jul 2017;59(1):R11-r31.

43.Jawaid A, Roszkowski M, Mansuy IM. Transgenerational Epigenetics of Traumatic Stress. Prog Mol Biol Transl Sci. 2018;158:273-298.

44.Youssef NA, Lockwood L, Su S, Hao G, Rutten BPF. The Effects of Trauma, with or without PTSD, on the Transgenerational DNA Methylation Alterations in Human Offsprings. Brain Sci. May 8 2018;8(5).

45.Epel ES, Lithgow GJ. Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity. J Gerontol A Biol Sci Med Sci. Jun 2014;69 Suppl 1:S10-16.

46.Peake JM, Markworth JF, Nosaka K, Raastad T, Wadley GD, Coffey VG. Modulating exercise-induced hormesis: Does less equal more J Appl Physiol (1985). Aug 1 2015;119(3):172-189.

47.Testa G, Biasi F, Poli G, Chiarpotto E. Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Curr Pharm Des. 2014;20(18):2950-2977.

48.Ristow M, Schmeisser S. Extending life span by increasing oxidative stress. Free Radic Biol Med. Jul 15 2011;51(2):327-336.

49.Lampert R, Tuit K, Hong KI, Donovan T, Lee F, Sinha R. Cumulative stress and autonomic dysregulation in a community sample. Stress. May 2016;19(3):269-279.

50.Fioranelli M, Bottaccioli AG, Bottaccioli F, Bianchi M, Rovesti M, Roccia MG. Stress and Inflammation in Coronary Artery Disease: A Review Psychoneuroendocrineimmunology-Based. Front Immunol. 2018;9:2031.

51.Kivimaki M, Kawachi I. Work Stress as a Risk Factor for Cardiovascular Disease. Curr Cardiol Rep. Sep 2015;17(9):630.

52.Virtanen M, Kivimaki M. Long Working Hours and Risk of Cardiovascular Disease. Curr Cardiol Rep. Oct 1 2018;20(11):123.

53.Nahrendorf M, Swirski FK. Lifestyle effects on hematopoiesis and atherosclerosis. Circ Res. Feb 27 2015;116(5):884-894.

54.Gopalakrishnan P, Zaidi R, Sardar MR. Takotsubo cardiomyopathy: Pathophysiology and role of cardiac biomarkers in differential diagnosis. World J Cardiol. Sep 26 2017;9(9):723-730.

55.Said SM, Saygili E, Rana OR, et al. Takotsubo Cardiomyopathy: What we have Learned in the Last 25 Years (A Comparative Literature Review). Curr Cardiol Rev. 2016;12(4):297-303.

56.Phillips C. Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging. Neural Plast. 2017;2017:3589271.

57.Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology (Berl). May 2016;233(9):1637-1650.

58.Piirainen S, Youssef A, Song C, et al. Psychosocial stress on neuroinflammation and cognitive dysfunctions in Alzheimer's disease: the emerging role for microglia Neurosci Biobehav Rev. Jun 2017;77:148-164.

59.Bisht K, Sharma K, Tremblay ME. Chronic stress as a risk factor for Alzheimer's disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress. Neurobiol Stress. Nov 2018;9:9-21.

60.Kumar A, Pareek V, Faiq MA, et al. Regulatory role of NGFs in neurocognitive functions. Rev Neurosci. Jul 26 2017;28(6):649-673.

61.Daskalakis NP, De Kloet ER, Yehuda R, Malaspina D, Kranz TM. Early Life Stress Effects on Glucocorticoid-BDNF Interplay in the Hippocampus. Front Mol Neurosci. 2015;8:68.

62.Nowacka M, Obuchowicz E. BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies. Pharmacol Rep. 2013;65(3):535-546.

63.Makhathini KB, Abboussi O, Stein DJ, Mabandla MV, Daniels WMU. Repetitive stress leads to impaired cognitive function that is associated with DNA hypomethylation, reduced BDNF and a dysregulated HPA axis. Int J Dev Neurosci. Aug 2017;60:63-69.

64.Eng JW, Kokolus KM, Reed CB, Hylander BL, Ma WW, Repasky EA. A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response. Cancer Immunol Immunother. Nov 2014;63(11):1115-1128.

65.Shin KJ, Lee YJ, Yang YR, et al. Molecular Mechanisms Underlying Psychological Stress and Cancer. Curr Pharm Des. 2016;22(16):2389-2402.

66.Stults-Kolehmainen MA, Sinha R. The effects of stress on physical activity and exercise. Sports Med. Jan 2014;44(1):81-121.

67.Mayo Clinic. Healthy Lifestyle: Stress Management. Available at https://www.mayoclinic.org/healthy-lifestyle/stress-management/in-depth/stress-symptoms/art-20050987. Last updated 04/28/2016. Accessed 11/05/2018. 2016.

68.Law E, Girgis A, Sylvie L, Levesque J, Pickett H. Telomeres and Stress: Promising Avenues for Research in Psycho-Oncology. Asia Pac J Oncol Nurs. Apr-Jun 2016;3(2):137-147.

69.Pirl WF, Fann JR, Greer JA, et al. Recommendations for the implementation of distress screening programs in cancer centers: report from the American Psychosocial Oncology Society (APOS), Association of Oncology Social Work (AOSW), and Oncology Nursing Society (ONS) joint task force. Cancer. Oct 1 2014;120(19):2946-2954.

70.Grassi L, Spiegel D, Riba M. Advancing psychosocial care in cancer patients. F1000Res. 2017;6:2083.

71.Lacourt TE, Heijnen CJ. Mechanisms of Neurotoxic Symptoms as a Result of Breast Cancer and Its Treatment: Considerations on the Contribution of Stress, Inflammation, and Cellular Bioenergetics. Curr Breast Cancer Rep. 2017;9(2):70-81.

72.Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. Sep 2018;15(9):505-522.

73.Ayroldi E, Cannarile L, Adorisio S, Delfino DV, Riccardi C. Role of Endogenous Glucocorticoids in Cancer in the Elderly. Int J Mol Sci. Nov 27 2018;19(12).

74.Del Pinto R, Ferri C. Inflammation-Accelerated Senescence and the Cardiovascular System: Mechanisms and Perspectives. Int J Mol Sci. Nov 22 2018;19(12).

75.Masri S, Sassone-Corsi P. The emerging link between cancer, metabolism, and circadian rhythms. Nat Med. Dec 2018;24(12):1795-1803.

76.Ans AH, Anjum I, Satija V, et al. Neurohormonal Regulation of Appetite and its Relationship with Stress: A Mini Literature Review. Cureus. Jul 23 2018;10(7):e3032.

77.Joseph JJ, Golden SH. Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus. Ann N Y Acad Sci. Mar 2017;1391(1):20-34.

78.Kargi AY, Iacobellis G. Adipose tissue and adrenal glands: novel pathophysiological mechanisms and clinical applications. Int J Endocrinol. 2014;2014:614074.

79.Champaneri S, Xu X, Carnethon MR, et al. Diurnal salivary cortisol is associated with body mass index and waist circumference: the Multiethnic Study of Atherosclerosis. Obesity (Silver Spring). Jan 2013;21(1):E56-63.

80.Lemche E, Chaban OS, Lemche AV. Neuroendorine and Epigentic Mechanisms Subserving Autonomic Imbalance and HPA Dysfunction in the Metabolic Syndrome. Front Neurosci. 2016;10:142.

81.Martocchia A, Stefanelli M, Falaschi GM, Toussan L, Ferri C, Falaschi P. Recent advances in the role of cortisol and metabolic syndrome in age-related degenerative diseases. Aging Clin Exp Res. Feb 2016;28(1):17-23.

82.Diz-Chaves Y, Gil-Lozano M, Toba L, et al. Stressing diabetes The hidden links between insulinotropic peptides and the HPA axis. J Endocrinol. Aug 2016;230(2):R77-94.

83.Abdulateef DS, Mahwi TO. Assessment of hair cortisol in euthyroid, hypothyroid, and subclinical hypothyroid subjects. Endocrine. Sep 6 2018.

84.Damian L, Ghiciuc CM, Dima-Cozma LC, et al. No definitive evidence for a connection between autoimmune thyroid diseases and stress in women. Neuro Endocrinol Lett. Jul 2016;37(3):155-162.

85.Johnson EO, Kamilaris TC, Calogero AE, Konstandi M, Chrousos GP. Effects of short- and long-duration hypothyroidism on function of the rat hypothalamic-pituitary-adrenal axis. J Endocrinol Invest. Feb 2013;36(2):104-110.

86.Johnson EO, Calogero AE, Konstandi M, Kamilaris TC, La Vignera S, Chrousos GP. Effects of short- and long-duration hypothyroidism on hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies. Endocrine. Dec 2012;42(3):684-693.

87.Rosenberg SL, Miller GE, Brehm JM, Celedon JC. Stress and asthma: novel insights on genetic, epigenetic, and immunologic mechanisms. J Allergy Clin Immunol. Nov 2014;134(5):1009-1015.

88.Lin TK, Zhong L, Santiago JL. Association between Stress and the HPA Axis in the Atopic Dermatitis. Int J Mol Sci. Oct 12 2017;18(10).

89.Sharif K, Watad A, Coplan L, et al. The role of stress in the mosaic of autoimmunity: An overlooked association. Autoimmun Rev. Oct 2018;17(10):967-983.

90.Romano GF, Tomassi S, Russell A, Mondelli V, Pariante CM. Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues. Adv Psychosom Med. 2015;34:61-77.

91.Stover CM. Mechanisms of Stress-Mediated Modulation of Upper and Lower Respiratory Tract Infections. Adv Exp Med Biol. 2016;874:215-223.

92.Sharma R, Biedenharn KR, Fedor JM, Agarwal A. Lifestyle factors and reproductive health: taking control of your fertility. Reprod Biol Endocrinol. Jul 16 2013;11:66.

93.Pellissier S, Bonaz B. The Place of Stress and Emotions in the Irritable Bowel Syndrome. Vitam Horm. 2017;103:327-354.

94.Maleki N, Becerra L, Borsook D. Migraine: maladaptive brain responses to stress. Headache. Oct 2012;52 Suppl 2(Suppl 2):102-106.

95.Burke NN, Finn DP, McGuire BE, Roche M. Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms. J Neurosci Res. Jun 2017;95(6):1257-1270.

96.Buscemi V, Chang WJ, Liston MB, McAuley JH, Schabrun S. The role of psychosocial stress in the development of chronic musculoskeletal pain disorders: protocol for a systematic review and meta-analysis. Syst Rev. Nov 3 2017;6(1):224.

97.Brotto L, Atallah S, Johnson-Agbakwu C, et al. Psychological and Interpersonal Dimensions of Sexual Function and Dysfunction. J Sex Med. Apr 2016;13(4):538-571.

98.Turpeinen U, Hamalainen E. Determination of cortisol in serum, saliva and urine. Best Pract Res Clin Endocrinol Metab. Dec 2013;27(6):795-801.

99.Wosu AC, Valdimarsdottir U, Shields AE, Williams DR, Williams MA. Correlates of cortisol in human hair: implications for epidemiologic studies on health effects of chronic stress. Ann Epidemiol. Dec 2013;23(12):797-811.e792.

100.Kim LU, D'Orsogna MR, Chou T. Onset, timing, and exposure therapy of stress disorders: mechanistic insight from a mathematical model of oscillating neuroendocrine dynamics. Biol Direct. 2016;11(1):13.

101.Inder WJ, Dimeski G, Russell A. Measurement of salivary cortisol in 2012 - laboratory techniques and clinical indications. Clin Endocrinol (Oxf). Nov 2012;77(5):645-651.

102.Golden SH, Wand GS, Malhotra S, Kamel I, Horton K. Reliability of hypothalamic-pituitary-adrenal axis assessment methods for use in population-based studies. Eur J Epidemiol. Jul 2011;26(7):511-525.

103.Adam EK, Quinn ME, Tavernier R, McQuillan MT, Dahlke KA, Gilbert KE. Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis. Psychoneuroendocrinology. Sep 2017;83:25-41.

104.Miller R, Stalder T, Jarczok M, et al. The CIRCORT database: Reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies. Psychoneuroendocrinology. Nov 2016;73:16-23.

105.Wright KD, Hickman R, Laudenslager ML. Hair Cortisol Analysis: A Promising Biomarker of HPA Activation in Older Adults. Gerontologist. Jun 2015;55 Suppl 1(Suppl 1):S140-145.

106.Wester VL, van Rossum EF. Clinical applications of cortisol measurements in hair. Eur J Endocrinol. Oct 2015;173(4):M1-10.

107.Silverman MN, Heim CM, Nater UM, Marques AH, Sternberg EM. Neuroendocrine and immune contributors to fatigue. Pm r. May 2010;2(5):338-346.

108.Keremi B, Beck A, Fabian TK, et al. Stress and Salivary Glands. Curr Pharm Des. Oct 30 2017;23(27):4057-4065.

109.Nater UM, Rohleder N. Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology. May 2009;34(4):486-496.

110.Schumacher S, Kirschbaum C, Fydrich T, Strohle A. Is salivary alpha-amylase an indicator of autonomic nervous system dysregulations in mental disorders--a review of preliminary findings and the interactions with cortisol. Psychoneuroendocrinology. Jun 2013;38(6):729-743.

111.Cozma S, Dima-Cozma LC, Ghiciuc CM, Pasquali V, Saponaro A, Patacchioli FR. Salivary cortisol and alpha-amylase: subclinical indicators of stress as cardiometabolic risk. Braz J Med Biol Res. Feb 6 2017;50(2):e5577.

112.Laufer S, Engel S, Knaevelsrud C, Schumacher S. Cortisol and alpha-amylase assessment in psychotherapeutic intervention studies: A systematic review. Neurosci Biobehav Rev. Dec 2018;95:235-262.

113.Paszynska E, Dmitrzak-Weglarz M, Tyszkiewicz-Nwafor M, Slopien A. Salivary alpha-amylase, secretory IgA and free cortisol as neurobiological components of the stress response in the acute phase of anorexia nervosa. World J Biol Psychiatry. Jun 2016;17(4):266-273.

114.Alaki SM, Safi A, Ouda S, Nadhreen A. Comparing Dental Stress in New Child Patients and Returning Patients Using Salivary Cortisol, Immunoglobulin-A and Alpha- Amylase. J Clin Pediatr Dent. 2017;41(6):462-466.

115.Watanabe K, Shirakawa T. Characteristics of Perceived Stress and Salivary Levels of Secretory Immunoglobulin A and Cortisol in Japanese Women With Premenstrual Syndrome. Nurs Midwifery Stud. Jun 2015;4(2):e24795.

116.Engeland CG, Hugo FN, Hilgert JB, et al. Psychological distress and salivary secretory immunity. Brain Behav Immun. Feb 2016;52:11-17.

117.Romero-Martinez A, Moya-Albiol L. Stress-Induced Endocrine and Immune Dysfunctions in Caregivers of People with Eating Disorders. Int J Environ Res Public Health. Dec 13 2017;14(12).

118.Strugnell RA, Wijburg OL. The role of secretory antibodies in infection immunity. Nat Rev Microbiol. Sep 2010;8(9):656-667.

119.Obayashi K. Salivary mental stress proteins. Clin Chim Acta. Oct 21 2013;425:196-201.

120.Strahler J, Skoluda N, Kappert MB, Nater UM. Simultaneous measurement of salivary cortisol and alpha-amylase: Application and recommendations. Neurosci Biobehav Rev. Dec 2017;83:657-677.

121.Lennartsson AK, Theorell T, Rockwood AL, Kushnir MM, Jonsdottir IH. Perceived stress at work is associated with lower levels of DHEA-S. PLoS One. 2013;8(8):e72460.

122.Mannic T, Viguie J, Rossier MF. In vivo and in vitro evidences of dehydroepiandrosterone protective role on the cardiovascular system. Int J Endocrinol Metab. Apr 2015;13(2):e24660.

123.Samaras N, Samaras D, Frangos E, Forster A, Philippe J. A review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: is treatment beneficial Rejuvenation Res. Aug 2013;16(4):285-294.

124.Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health. 2017;5:258.

125.Kim HG, Cheon EJ, Bai DS, Lee YH, Koo BH. Stress and Heart Rate Variability: A Meta-Analysis and Review of the Literature. Psychiatry Investig. Mar 2018;15(3):235-245.

126.Siegrist J, Li J. Work Stress and Altered Biomarkers: A Synthesis of Findings Based on the Effort-Reward Imbalance Model. Int J Environ Res Public Health. Nov 10 2017;14(11).

127.Balzarotti S, Biassoni F, Colombo B, Ciceri MR. Cardiac vagal control as a marker of emotion regulation in healthy adults: A review. Biol Psychol. Dec 2017;130:54-66.

128.Perez-Quilis C, Kingsley JD, Malkani K, Cervellin G, Lippi G, Sanchis-Gomar F. Modulation of Heart Rate by Acute or Chronic Aerobic Exercise. Potential Effects on Blood Pressure Control. Curr Pharm Des. 2017;23(31):4650-4657.

129.Heckenberg RA, Eddy P, Kent S, Wright BJ. Do workplace-based mindfulness meditation programs improve physiological indices of stress A systematic review and meta-analysis. J Psychosom Res. Nov 2018;114:62-71.

130.Carnevali L, Koenig J, Sgoifo A, Ottaviani C. Autonomic and Brain Morphological Predictors of Stress Resilience. Front Neurosci. 2018;12:228.

131.Cadegiani FA, Kater CE. Adrenal fatigue does not exist: a systematic review. BMC Endocr Disord. Aug 24 2016;16(1):48.

132.Powell DJ, Liossi C, Moss-Morris R, Schlotz W. Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: a systematic review and subset meta-analysis. Psychoneuroendocrinology. Nov 2013;38(11):2405-2422.

133.Munir S, Waseem M. Addison Disease. StatPearls. Treasure Island (FL): StatPearls Publishing LLC.; 2018.

134.Koen N, Stein DJ. Pharmacotherapy of anxiety disorders: a critical review. Dialogues Clin Neurosci. 2011;13(4):423-437.

135.Rougemont-Bucking A, Gamma F, Panksepp J. Use of tramadol in psychiatric care: A comprehensive review and report of two cases. Swiss Med Wkly. 2017;147:w14428.

136.Santarsieri D, Schwartz TL. Antidepressant efficacy and side-effect burden: a quick guide for clinicians. Drugs Context. 2015;4:212290.

137.Kirilly E, Gonda X, Bagdy G. [Antidepressants, stressors and the serotonin 1A receptor]. Neuropsychopharmacol Hung. Jun 2015;17(2):81-89.

138.Gupta D, Radhakrishnan M, Bhatt S, Kurhe Y. Role of Hypothalamic-pituitary-adrenal-axis in Affective Disorders: Anti-depressant and Anxiolytic Activity of Partial 5-HT1A Agonist in Adrenalectomised Rats. Indian J Psychol Med. Jul 2013;35(3):290-298.

139.Mayo Clinic. Buspirone (Oral Route): Side Effects. Available at https://www.mayoclinic.org/drugs-supplements/buspirone-oral-route/side-effects/drg-20062457. Last updated 10/1/2018. Accessed 12/27/2018. 2018.

140.Bossini L, Coluccia A, Casolaro I, et al. Off-Label Trazodone Prescription: Evidence, Benefits and Risks. Curr Pharm Des. 2015;21(23):3343-3351.

141.Khouzam HR. A review of trazodone use in psychiatric and medical conditions. Postgrad Med. Jan 2017;129(1):140-148.

142.Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A. Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. J Psychopharmacol. Feb 2016;30(2):128-139.

143.Mayo Clinic. Beta Blockers. Available at https://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/beta-blockers/art-20044522. Last updates 4/6/2018. Accessed 12/22/18. 2018.

144.Akbar S, Alorainy MS. The current status of beta blockers' use in the management of hypertension. Saudi Med J. Nov 2014;35(11):1307-1317.

145.Dudek D, Jaeschke R, Styczen K, Pilecki M. Depression and anxiety in the practice of cardiology. Kardiol Pol. 2013;71(8):781-786.

146.Celano CM, Daunis DJ, Lokko HN, Campbell KA, Huffman JC. Anxiety Disorders and Cardiovascular Disease. Curr Psychiatry Rep. Nov 2016;18(11):101.

147.Dell'Osso B, Albert U, Atti AR, et al. Bridging the gap between education and appropriate use of benzodiazepines in psychiatric clinical practice. Neuropsychiatr Dis Treat. 2015;11:1885-1909.

148.Ramirez K, Niraula A, Sheridan JF. GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations. Brain Behav Immun. Jan 2016;51:154-168.

149.Jung S, Spence MM, Escasa NM, Lee EA, Hui RL, Gibbs NE. The Risk of Pneumonia in Older Adults Using Nonbenzodiazepine Hypnotics. J Manag Care Spec Pharm. Aug 2016;22(8):932-938.

150.Kuntz J, Kouch L, Christian D, Peterson PL, Gruss I. Barriers and Facilitators to the Deprescribing of Nonbenzodiazepine Sedative Medications Among Older Adults. Perm J. 2018;22.

151.Wilt TJ, MacDonald R, Brasure M, et al. Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians. Ann Intern Med. Jul 19 2016;165(2):103-112.

152.Cleare AJ, Miell J, Heap E, et al. Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy. J Clin Endocrinol Metab. Aug 2001;86(8):3545-3554.

153.Blockmans D, Persoons P, Van Houdenhove B, Lejeune M, Bobbaers H. Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study. Am J Med. Jun 15 2003;114(9):736-741.

154.McKenzie R, O'Fallon A, Dale J, et al. Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial. Jama. Sep 23-30 1998;280(12):1061-1066.

155.Hofmann SG, Asnaani A, Vonk IJ, Sawyer AT, Fang A. The Efficacy of Cognitive Behavioral Therapy: A Review of Meta-analyses. Cognit Ther Res. Oct 1 2012;36(5):427-440.

156.Lindsater E, Axelsson E, Salomonsson S, et al. Internet-Based Cognitive Behavioral Therapy for Chronic Stress: A Randomized Controlled Trial. Psychother Psychosom. 2018;87(5):296-305.

157.Anclair M, Lappalainen R, Muotka J, Hiltunen AJ. Cognitive behavioural therapy and mindfulness for stress and burnout: a waiting list controlled pilot study comparing treatments for parents of children with chronic conditions. Scand J Caring Sci. Mar 2018;32(1):389-396.

158.Carpenter JK, Andrews LA, Witcraft SM, Powers MB, Smits JAJ, Hofmann SG. Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials. Depress Anxiety. Jun 2018;35(6):502-514.

159.Baker N. Using Cognitive Behavior Therapy and Mindfulness Techniques in the Management of Chronic Pain in Primary Care. Prim Care. Jun 2016;43(2):203-216.

160.Eller-Smith OC, Nicol AL, Christianson JA. Potential Mechanisms Underlying Centralized Pain and Emerging Therapeutic Interventions. Front Cell Neurosci. 2018;12:35.

161.Karlsson B, Burell G, Anderberg UM, Svardsudd K. Cognitive behaviour therapy in women with fibromyalgia: A randomized clinical trial. Scand J Pain. Oct 1 2015;9(1):11-21.

162.Schiller H, Soderstrom M, Lekander M, Rajaleid K, Kecklund G. A randomized controlled intervention of workplace-based group cognitive behavioral therapy for insomnia. Int Arch Occup Environ Health. May 2018;91(4):413-424.

163.Bishop JR, Lee AM, Mills LJ, et al. Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder. Front Psychiatry. 2018;9:418.

164.Bergen-Cico D, Possemato K, Pigeon W. Reductions in cortisol associated with primary care brief mindfulness program for veterans with PTSD. Med Care. Dec 2014;52(12 Suppl 5):S25-31.

165.Pascoe MC, Thompson DR, Jenkins ZM, Ski CF. Mindfulness mediates the physiological markers of stress: Systematic review and meta-analysis. J Psychiatr Res. Dec 2017;95:156-178.

166.Levine GN, Lange RA, Bairey-Merz CN, et al. Meditation and Cardiovascular Risk Reduction: A Scientific Statement From the American Heart Association. J Am Heart Assoc. Sep 28 2017;6(10).

167.Guillaumie L, Boiral O, Champagne J. A mixed-methods systematic review of the effects of mindfulness on nurses. J Adv Nurs. May 2017;73(5):1017-1034.

168.Lamothe M, Rondeau E, Malboeuf-Hurtubise C, Duval M, Sultan S. Outcomes of MBSR or MBSR-based interventions in health care providers: A systematic review with a focus on empathy and emotional competencies. Complement Ther Med. Feb 2016;24:19-28.

169.Janssen M, Heerkens Y, Kuijer W, van der Heijden B, Engels J. Effects of Mindfulness-Based Stress Reduction on employees' mental health: A systematic review. PLoS One. 2018;13(1):e0191332.

170.Ravalier JM, Wegrzynek P, Lawton S. Systematic review: complementary therapies and employee well-being. Occup Med (Lond). Aug 2016;66(6):428-436.

171.Daubenmier J, Kristeller J, Hecht FM, et al. Mindfulness Intervention for Stress Eating to Reduce Cortisol and Abdominal Fat among Overweight and Obese Women: An Exploratory Randomized Controlled Study. J Obes. 2011;2011:651936.

172.Fish J, Brimson J, Lynch S. Mindfulness Interventions Delivered by Technology Without Facilitator Involvement: What Research Exists and What Are the Clinical Outcomes Mindfulness (N Y). 2016;7(5):1011-1023.

173.Carolan S, Harris PR, Cavanagh K. Improving Employee Well-Being and Effectiveness: Systematic Review and Meta-Analysis of Web-Based Psychological Interventions Delivered in the Workplace. J Med Internet Res. Jul 26 2017;19(7):e271.

174.Heber E, Ebert DD, Lehr D, et al. The Benefit of Web- and Computer-Based Interventions for Stress: A Systematic Review and Meta-Analysis. J Med Internet Res. Feb 17 2017;19(2):e32.

175.Huffman DM, Schafer MJ, LeBrasseur NK. Energetic interventions for healthspan and resiliency with aging. Exp Gerontol. Dec 15 2016;86:73-83.

176.Stubbs B, Vancampfort D, Rosenbaum S, et al. An examination of the anxiolytic effects of exercise for people with anxiety and stress-related disorders: A meta-analysis. Psychiatry Res. Mar 2017;249:102-108.

177.Ortega E. The "bioregulatory effect of exercise" on the innate/inflammatory responses. J Physiol Biochem. Jun 2016;72(2):361-369.

178.Kline CE. The bidirectional relationship between exercise and sleep: Implications for exercise adherence and sleep improvement. Am J Lifestyle Med. Nov-Dec 2014;8(6):375-379.

179.Asmundson GJ, Fetzner MG, Deboer LB, Powers MB, Otto MW, Smits JA. Let's get physical: a contemporary review of the anxiolytic effects of exercise for anxiety and its disorders. Depress Anxiety. Apr 2013;30(4):362-373.

180.Mikkelsen K, Stojanovska L, Polenakovic M, Bosevski M, Apostolopoulos V. Exercise and mental health. Maturitas. Dec 2017;106:48-56.

181.Huang CJ, Webb HE, Zourdos MC, Acevedo EO. Cardiovascular reactivity, stress, and physical activity. Front Physiol. Nov 7 2013;4:314.

182.Bernard P, Dore I, Romain AJ, Hains-Monfette G, Kingsbury C, Sabiston C. Dose response association of objective physical activity with mental health in a representative national sample of adults: A cross-sectional study. PLoS One. 2018;13(10):e0204682.

183.Gordon BR, McDowell CP, Lyons M, Herring MP. The Effects of Resistance Exercise Training on Anxiety: A Meta-Analysis and Meta-Regression Analysis of Randomized Controlled Trials. Sports Med. Dec 2017;47(12):2521-2532.

184.Kovacevic A, Mavros Y, Heisz JJ, Fiatarone Singh MA. The effect of resistance exercise on sleep: A systematic review of randomized controlled trials. Sleep Med Rev. Jun 2018;39:52-68.

185.Leow S, Jackson B, Alderson JA, Guelfi KJ, Dimmock JA. A Role for Exercise in Attenuating Unhealthy Food Consumption in Response to Stress. Nutrients. Feb 6 2018;10(2).

186.van Praag H, Fleshner M, Schwartz MW, Mattson MP. Exercise, energy intake, glucose homeostasis, and the brain. J Neurosci. Nov 12 2014;34(46):15139-15149.

187.Wasfy MM, Baggish AL. Exercise Dose in Clinical Practice. Circulation. Jun 7 2016;133(23):2297-2313.

188.Mitchell M, White L, Lau E, Leahey T, Adams MA, Faulkner G. Evaluating the Carrot Rewards App, a Population-Level Incentive-Based Intervention Promoting Step Counts Across Two Canadian Provinces: Quasi-Experimental Study. JMIR Mhealth Uhealth. Sep 20 2018;6(9):e178.

189.Kramer JN, Tinschert P, Scholz U, Fleisch E, Kowatsch T. A Cluster-Randomized Trial on Small Incentives to Promote Physical Activity. Am J Prev Med. Dec 13 2018.

190.Yuenyongchaiwat K. Effects of 10,000 steps a day on physical and mental health in overweight participants in a community setting: a preliminary study. Braz J Phys Ther. Jul-Aug 2016;20(4):367-373.

191.Liau AK, Neihart M, Teo CT, Goh LS, Chew P. A Quasi-Experimental Study of a Fitbit-Based Self-Regulation Intervention to Improve Physical Activity, Well-Being, and Mental Health. Cyberpsychol Behav Soc Netw. Nov 2018;21(11):727-734.

192.Friedman E, Krause-Parello CA. Companion animals and human health: benefits, challenges, and the road ahead for human-animal interaction. Rev Sci Tech. Apr 2018;37(1):71-82.

193.Ogechi I, Snook K, Davis BM, Hansen AR, Liu F, Zhang J. Pet Ownership and the Risk of Dying from Cardiovascular Disease Among Adults Without Major Chronic Medical Conditions. High Blood Press Cardiovasc Prev. Sep 2016;23(3):245-253.

194.Qureshi AI, Memon MZ, Vazquez G, Suri MF. Cat ownership and the Risk of Fatal Cardiovascular Diseases. Results from the Second National Health and Nutrition Examination Study Mortality Follow-up Study. J Vasc Interv Neurol. Jan 2009;2(1):132-135.

195.Arhant-Sudhir K, Arhant-Sudhir R, Sudhir K. Pet ownership and cardiovascular risk reduction: supporting evidence, conflicting data and underlying mechanisms. Clin Exp Pharmacol Physiol. Nov 2011;38(11):734-738.

196.Virues-Ortega J, Buela-Casal G. Psychophysiological effects of human-animal interaction: theoretical issues and long-term interaction effects. J Nerv Ment Dis. Jan 2006;194(1):52-57.

197.Pickering TG. Men are from Mars, women are from Venus: stress, pets, and oxytocin. J Clin Hypertens (Greenwich). Jan-Feb 2003;5(1):86-88.

198.Lundqvist M, Carlsson P, Sjodahl R, Theodorsson E, Levin LA. Patient benefit of dog-assisted interventions in health care: a systematic review. BMC Complement Altern Med. Jul 10 2017;17(1):358.

199.Polheber JP, Matchock RL. The presence of a dog attenuates cortisol and heart rate in the Trier Social Stress Test compared to human friends. J Behav Med. Oct 2014;37(5):860-867.

200.Allen K, Blascovich J, Mendes WB. Cardiovascular reactivity and the presence of pets, friends, and spouses: the truth about cats and dogs. Psychosom Med. Sep-Oct 2002;64(5):727-739.

201.Oyola MG, Handa RJ. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity. Stress. Sep 2017;20(5):476-494.

202.Toufexis D, Rivarola MA, Lara H, Viau V. Stress and the reproductive axis. J Neuroendocrinol. Sep 2014;26(9):573-586.

203.Stephens MA, Mahon PB, McCaul ME, Wand GS. Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones. Psychoneuroendocrinology. Apr 2016;66:47-55.

204.Wirth MM. Beyond the HPA Axis: Progesterone-Derived Neuroactive Steroids in Human Stress and Emotion. Front Endocrinol (Lausanne). 2011;2:19.

205.Ziomkiewicz A, Pawlowski B, Ellison PT, Lipson SF, Thune I, Jasienska G. Higher luteal progesterone is associated with low levels of premenstrual aggressive behavior and fatigue. Biol Psychol. Dec 2012;91(3):376-382.

206.Patacchioli FR, Ghiciuc CM, Bernardi M, et al. Salivary alpha-amylase and cortisol after exercise in menopause: influence of long-term HRT. Climacteric. 2015;18(4):528-535.

207.Herrera AY, Hodis HN, Mack WJ, Mather M. Estradiol Therapy After Menopause Mitigates Effects of Stress on Cortisol and Working Memory. J Clin Endocrinol Metab. Dec 1 2017;102(12):4457-4466.

208.Steffen AM, Thompson LW, Gallagher-Thompson D, Koin D. Physical and psychosocial correlates of hormone replacement therapy with chronically stressed postmenopausal women. J Aging Health. Feb 1999;11(1):3-26.

209.Prior JC. Progesterone for Symptomatic Perimenopause Treatment - Progesterone politics, physiology and potential for perimenopause. Facts Views Vis Obgyn. 2011;3(2):109-120.

210.Leeangkoonsathian E, Pantasri T, Chaovisitseree S, Morakot N. The effect of different progestogens on sleep in postmenopausal women: a randomized trial. Gynecol Endocrinol. Dec 2017;33(12):933-936.

211.Espinosa-Garcia C, Sayeed I, Yousuf S, et al. Stress primes microglial polarization after global ischemia: Therapeutic potential of progesterone. Brain Behav Immun. Nov 2017;66:177-192.

212.Tomiyama AJ, Dallman MF, Epel ES. Comfort food is comforting to those most stressed: evidence of the chronic stress response network in high stress women. Psychoneuroendocrinology. Nov 2011;36(10):1513-1519.

213.Jaremka LM, Belury MA, Andridge RR, et al. Interpersonal stressors predict ghrelin and leptin levels in women. Psychoneuroendocrinology. Oct 2014;48:178-188.

214.Yau YH, Potenza MN. Stress and eating behaviors. Minerva Endocrinol. Sep 2013;38(3):255-267.

215.Tryon MS, DeCant R, Laugero KD. Having your cake and eating it too: a habit of comfort food may link chronic social stress exposure and acute stress-induced cortisol hyporesponsiveness. Physiol Behav. Apr 10 2013;114-115:32-37.

216.Tryon MS, Stanhope KL, Epel ES, et al. Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain and Body. J Clin Endocrinol Metab. Jun 2015;100(6):2239-2247.

217.Errisuriz VL, Pasch KE, Perry CL. Perceived stress and dietary choices: The moderating role of stress management. Eat Behav. Aug 2016;22:211-216.

218.Aschbacher K, Kornfeld S, Picard M, et al. Chronic stress increases vulnerability to diet-related abdominal fat, oxidative stress, and metabolic risk. Psychoneuroendocrinology. Aug 2014;46:14-22.

219.Wang J, Um P, Dickerman BA, Liu J. Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications. Nutrients. May 9 2018;10(5).

220.Singh K. Nutrient and Stress Management. J Nutr Food Sci. 2016;6(4).

221.Conner TS, Brookie KL, Carr AC, Mainvil LA, Vissers MC. Let them eat fruit! The effect of fruit and vegetable consumption on psychological well-being in young adults: A randomized controlled trial. PLoS One. 2017;12(2):e0171206.

222.Garcia-Prieto MD, Tebar FJ, Nicolas F, Larque E, Zamora S, Garaulet M. Cortisol secretary pattern and glucocorticoid feedback sensitivity in women from a Mediterranean area: relationship with anthropometric characteristics, dietary intake and plasma fatty acid profile. Clin Endocrinol (Oxf). Feb 2007;66(2):185-191.

223.Carvalho KMB, Ronca DB, Michels N, et al. Does the Mediterranean Diet Protect against Stress-Induced Inflammatory Activation in European Adolescents The HELENA Study. Nutrients. Nov 15 2018;10(11).

224.Martucci M, Ostan R, Biondi F, et al. Mediterranean diet and inflammaging within the hormesis paradigm. Nutr Rev. Jun 1 2017;75(6):442-455.

225.Chaplin K, Smith AP. Breakfast and snacks: associations with cognitive failures, minor injuries, accidents and stress. Nutrients. May 2011;3(5):515-528.

226.Witbracht M, Keim NL, Forester S, Widaman A, Laugero K. Female breakfast skippers display a disrupted cortisol rhythm and elevated blood pressure. Physiol Behav. Mar 1 2015;140:215-221.

227.Nehlig A. Effects of coffee/caffeine on brain health and disease: What should I tell my patients Pract Neurol. Apr 2016;16(2):89-95.

228.Yang A, Palmer AA, de Wit H. Genetics of caffeine consumption and responses to caffeine. Psychopharmacology (Berl). Aug 2010;211(3):245-257.

229.al'Absi M, & Lovallo, W. R. . Caffeine's effects on the human stress axis. In A. Nehlig (Ed.), Nutrition, brain, and behavior. Coffee, tea, chocolate, and the brain (pp. 113-131). Boca Raton, FL, US: CRC Press. http://dx.doi.org/10.1201/9780203618851.ch8. 2004.

230.Lovallo WR, Whitsett TL, al'Absi M, Sung BH, Vincent AS, Wilson MF. Caffeine stimulation of cortisol secretion across the waking hours in relation to caffeine intake levels. Psychosom Med. Sep-Oct 2005;67(5):734-739.

231.Lovallo WR, Farag NH, Vincent AS, Thomas TL, Wilson MF. Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women. Pharmacol Biochem Behav. Mar 2006;83(3):441-447.

232.Gonzaga LA, Vanderlei LCM, Gomes RL, Valenti VE. Caffeine affects autonomic control of heart rate and blood pressure recovery after aerobic exercise in young adults: a crossover study. Sci Rep. Oct 26 2017;7(1):14091.

233.Hamer M, Williams ED, Vuononvirta R, Gibson EL, Steptoe A. Association between coffee consumption and markers of inflammation and cardiovascular function during mental stress. J Hypertens. Nov 2006;24(11):2191-2197.

234.Beaudoin MS, Graham TE. Methylxanthines and human health: epidemiological and experimental evidence. Handb Exp Pharmacol. 2011(200):509-548.

235.Schrieks IC, Joosten MM, Klopping-Ketelaars WA, Witkamp RF, Hendriks HF. Moderate alcohol consumption after a mental stressor attenuates the endocrine stress response. Alcohol. Dec 2016;57:29-34.

236.Kokavec A, Crowe SF. The effect of a moderate level of white wine consumption on the hypothalamic-pituitary-adrenal axis before and after a meal. Pharmacol Biochem Behav. Oct-Nov 2001;70(2-3):243-250.

237.Cupic Z, Stanojevic A, Markovic VM, Kolar-Anic L, Terenius L, Vukojevic V. The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations. Addict Biol. Nov 2017;22(6):1486-1500.

238.Rachdaoui N, Sarkar DK. Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System. Alcohol Res. 2017;38(2):255-276.

239.Blaine SK, Sinha R. Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders. Neuropharmacology. Aug 1 2017;122:136-147.

240.Hipson WE, Fisher DJ. The association between acute stress-related insomnia and alcohol use. Sleep Health. Sep 2016;2(3):246-252.

241.Keyes KM, Hatzenbuehler ML, Grant BF, Hasin DS. Stress and alcohol: epidemiologic evidence. Alcohol Res. 2012;34(4):391-400.

242.Leahy LG. Vitamin B Supplementation: What's the Right Choice for Your Patients J Psychosoc Nurs Ment Health Serv. Jul 1 2017;55(7):7-11.

243.Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review. Nutrients. Jan 27 2016;8(2):68.

244.Macpherson H, Rowsell R, Cox KH, et al. The Effects of Four-Week Multivitamin Supplementation on Mood in Healthy Older Women: A Randomized Controlled Trial. Evid Based Complement Alternat Med. 2016;2016:3092828.

245.Macpherson H, Rowsell R, Cox KH, Scholey A, Pipingas A. Acute mood but not cognitive improvements following administration of a single multivitamin and mineral supplement in healthy women aged 50 and above: a randomised controlled trial. Age (Dordr). Jun 2015;37(3):9782.

246.Pipingas A, Camfield DA, Stough C, et al. The effects of multivitamin supplementation on mood and general well-being in healthy young adults. A laboratory and at-home mobile phone assessment. Appetite. Oct 2013;69:123-136.

247.Sarris J, Cox KH, Camfield DA, et al. Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial. Nutr J. Dec 14 2012;11:110.

248.Harris E, Kirk J, Rowsell R, et al. The effect of multivitamin supplementation on mood and stress in healthy older men. Hum Psychopharmacol. Dec 2011;26(8):560-567.

249.Stough C, Scholey A, Lloyd J, Spong J, Myers S, Downey LA. The effect of 90 day administration of a high dose vitamin B-complex on work stress. Hum Psychopharmacol. Oct 2011;26(7):470-476.

250.Long SJ, Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: a meta-analysis. Psychosom Med. Feb 2013;75(2):144-153.

251.Camfield DA, Wetherell MA, Scholey AB, et al. The effects of multivitamin supplementation on diurnal cortisol secretion and perceived stress. Nutrients. Nov 11 2013;5(11):4429-4450.

252.Li X, Huang WX, Lu JM, et al. Effects of a multivitamin/multimineral supplement on young males with physical overtraining: a placebo-controlled, randomized, double-blinded cross-over trial. Biomed Environ Sci. Jul 2013;26(7):599-604.

253.Figueroa-Méndez R, Rivas-Arancibia S. Vitamin C in Health and Disease: Its Role in the Metabolism of Cells and Redox State in the Brain. Front Physiol. 2015;6:397.

254.Kocot J, Luchowska-Kocot D, Kielczykowska M, Musik I, Kurzepa J. Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders Nutrients. Jun 27 2017;9(7).

255.Han QQ, Shen TT, Wang F, Wu PF, Chen JG. Preventive and Therapeutic Potential of Vitamin C in Mental Disorders. Curr Med Sci. Feb 2018;38(1):1-10.

256.Chambial S, Dwivedi S, Shukla KK, John PJ, Sharma P. Vitamin C in disease prevention and cure: an overview. Indian J Clin Biochem. Oct 2013;28(4):314-328.

257.Gautam M, Agrawal M, Gautam M, Sharma P, Gautam AS, Gautam S. Role of antioxidants in generalised anxiety disorder and depression. Indian J Psychiatry. Jul 2012;54(3):244-247.

258.de Oliveira IJ, de Souza VV, Motta V, Da-Silva SL. Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial. Pak J Biol Sci. Jan 2015;18(1):11-18.

259.McCabe D, Lisy K, Lockwood C, Colbeck M. The impact of essential fatty acid, B vitamins, vitamin C, magnesium and zinc supplementation on stress levels in women: a systematic review. JBI Database System Rev Implement Rep. Feb 2017;15(2):402-453.

260.Taylor AM, Holscher HD. A review of dietary and microbial connections to depression, anxiety, and stress. Nutr Neurosci. Jul 9 2018:1-14.

261.Husted KS, Bouzinova EV. The importance of n-6/n-3 fatty acids ratio in the major depressive disorder. Medicina (Kaunas). 2016;52(3):139-147.

262.Su KP, Matsuoka Y, Pae CU. Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders. Clin Psychopharmacol Neurosci. Aug 31 2015;13(2):129-137.

263.Thesing CS, Bot M, Milaneschi Y, Giltay EJ, Penninx B. Omega-3 polyunsaturated fatty acid levels and dysregulations in biological stress systems. Psychoneuroendocrinology. Nov 2018;97:206-215.

264.Fernandes MF, Mutch DM, Leri F. The Relationship between Fatty Acids and Different Depression-Related Brain Regions, and Their Potential Role as Biomarkers of Response to Antidepressants. Nutrients. Mar 17 2017;9(3).

265.Sauder KA, Skulas-Ray AC, Campbell TS, Johnson JA, Kris-Etherton PM, West SG. Effects of omega-3 fatty acid supplementation on heart rate variability at rest and during acute stress in adults with moderate hypertriglyceridemia. Psychosom Med. May 2013;75(4):382-389.

266.Barbadoro P, Annino I, Ponzio E, et al. Fish oil supplementation reduces cortisol basal levels and perceived stress: a randomized, placebo-controlled trial in abstinent alcoholics. Mol Nutr Food Res. Jun 2013;57(6):1110-1114.

267.Mocking RJ, Verburg HF, Westerink AM, et al. Fatty acid metabolism and its longitudinal relationship with the hypothalamic-pituitary-adrenal axis in major depression: Associations with prospective antidepressant response. Psychoneuroendocrinology. Sep 2015;59:1-13.

268.Turkozu D, Sanlier N. L-theanine, unique amino acid of tea, and its metabolism, health effects, and safety. Crit Rev Food Sci Nutr. May 24 2017;57(8):1681-1687.

269.Unno K, Tanida N, Ishii N, et al. Anti-stress effect of theanine on students during pharmacy practice: positive correlation among salivary alpha-amylase activity, trait anxiety and subjective stress. Pharmacol Biochem Behav. Oct 2013;111:128-135.

270.White DJ, de Klerk S, Woods W, Gondalia S, Noonan C, Scholey AB. Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial. Nutrients. Jan 19 2016;8(1).

271.Giles GE, Mahoney CR, Brunye TT, Taylor HA, Kanarek RB. Caffeine and theanine exert opposite effects on attention under emotional arousal. Can J Physiol Pharmacol. Jan 2017;95(1):93-100.

272.Cicero AF, Bove M, Colletti A, et al. Short-Term Impact of a Combined Nutraceutical on Cognitive Function, Perceived Stress and Depression in Young Elderly with Cognitive Impairment: A Pilot, Double-Blind, Randomized Clinical Trial. J Prev Alzheimers Dis. 2017;4(1):12-15.

273.Kingsley M. Effects of phosphatidylserine supplementation on exercising humans. Sports Med. 2006;36(8):657-669.

274.Hellhammer J, Vogt D, Franz N, Freitas U, Rutenberg D. A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: a randomized, placebo-controlled study. Lipids Health Dis. Jul 31 2014;13:121.

275.Hellhammer J, Fries E, Buss C, et al. Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress. Jun 2004;7(2):119-126.

276.Benton D, Donohoe RT, Sillance B, Nabb S. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci. 2001;4(3):169-178.

277.Starks MA, Starks SL, Kingsley M, Purpura M, Jager R. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr. Jul 28 2008;5:11.

278.Porter RJ, Gallagher P, Watson S, Young AH. Corticosteroid-serotonin interactions in depression: a review of the human evidence. Psychopharmacology (Berl). Apr 2004;173(1-2):1-17.

279.Michels N, Clarke G, Olavarria-Ramirez L, et al. Psychosocial stress and inflammation driving tryptophan breakdown in children and adolescents: A cross-sectional analysis of two cohorts. Psychoneuroendocrinology. Aug 2018;94:104-111.

280.Hood SD, Hince DA, Robinson H, Cirillo M, Christmas D, Kaye JM. Serotonin regulation of the human stress response. Psychoneuroendocrinology. Oct 2006;31(9):1087-1097.

281.Capello AE, Markus CR. Effect of sub chronic tryptophan supplementation on stress-induced cortisol and appetite in subjects differing in 5-HTTLPR genotype and trait neuroticism. Psychoneuroendocrinology. Jul 2014;45:96-107.

282.Cerit H, Jans LA, Van der Does W. The effect of tryptophan on the cortisol response to social stress is modulated by the 5-HTTLPR genotype. Psychoneuroendocrinology. Feb 2013;38(2):201-208.

283.Markus CR, Firk C. Differential effects of tri-allelic 5-HTTLPR polymorphisms in healthy subjects on mood and stress performance after tryptophan challenge. Neuropsychopharmacology. Dec 2009;34(13):2667-2674.

284.Firk C, Markus CR. Mood and cortisol responses following tryptophan-rich hydrolyzed protein and acute stress in healthy subjects with high and low cognitive reactivity to depression. Clin Nutr. Jun 2009;28(3):266-271.

285.Mohanty DP, Mohapatra S, Misra S, Sahu PS. Milk derived bioactive peptides and their impact on human health - A review. Saudi J Biol Sci. Sep 2016;23(5):577-583.

286.Layman DK, Lonnerdal B, Fernstrom JD. Applications for alpha-lactalbumin in human nutrition. Nutr Rev. Jun 1 2018;76(6):444-460.

287.Yayeh T, Leem YH, Kim KM, et al. Administration of Alphas1-Casein Hydrolysate Increases Sleep and Modulates GABAA Receptor Subunit Expression. Biomol Ther (Seoul). May 1 2018;26(3):268-273.

288.Dela Pena IJ, Kim HJ, de la Pena JB, et al. A tryptic hydrolysate from bovine milk alphas1-casein enhances pentobarbital-induced sleep in mice via the GABAA receptor. Behav Brain Res. Oct 15 2016;313:184-190.

289.Guesdon B, Messaoudi M, Lefranc-Millot C, Fromentin G, Tome D, Even PC. A tryptic hydrolysate from bovine milk alphaS1-casein improves sleep in rats subjected to chronic mild stress. Peptides. Jun 2006;27(6):1476-1482.

290.Kim JH, Desor D, Kim YT, et al. Efficacy of alphas1-casein hydrolysate on stress-related symptoms in women. Eur J Clin Nutr. Apr 2007;61(4):536-541.

291.Messaoudi M, Lefranc-Millot C, Desor D, Demagny B, Bourdon L. Effects of a tryptic hydrolysate from bovine milk alphaS1-casein on hemodynamic responses in healthy human volunteers facing successive mental and physical stress situations. Eur J Nutr. Mar 2005;44(2):128-132.

292.Misra S, Mohanty D. Psychobiotics: A new approach for treating mental illness Crit Rev Food Sci Nutr. Nov 30 2017:1-7.

293.Takada M, Nishida K, Kataoka-Kato A, et al. Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models. Neurogastroenterol Motil. Jul 2016;28(7):1027-1036.

294.Kato-Kataoka A, Nishida K, Takada M, et al. Fermented milk containing Lactobacillus casei strain Shirota prevents the onset of physical symptoms in medical students under academic examination stress. Benef Microbes. 2016;7(2):153-156.

295.Kato-Kataoka A, Nishida K, Takada M, et al. Fermented Milk Containing Lactobacillus casei Strain Shirota Preserves the Diversity of the Gut Microbiota and Relieves Abdominal Dysfunction in Healthy Medical Students Exposed to Academic Stress. Appl Environ Microbiol. Jun 15 2016;82(12):3649-3658.

296.Andersson H, Tullberg C, Ahrne S, et al. Oral Administration of Lactobacillus plantarum 299v Reduces Cortisol Levels in Human Saliva during Examination Induced Stress: A Randomized, Double-Blind Controlled Trial. Int J Microbiol. 2016;2016:8469018.

297.Messaoudi M, Lalonde R, Violle N, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. Mar 2011;105(5):755-764.

298.Allen AP, Hutch W, Borre YE, et al. Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Transl Psychiatry. Nov 1 2016;6(11):e939.

299.Schmidt K, Cowen PJ, Harmer CJ, Tzortzis G, Errington S, Burnet PW. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl). May 2015;232(10):1793-1801.

300.Gamble KL, Berry R, Frank SJ, Young ME. Circadian clock control of endocrine factors. Nat Rev Endocrinol. Aug 2014;10(8):466-475.

301.Hardeland R. Melatonin in aging and disease -multiple consequences of reduced secretion, options and limits of treatment. Aging Dis. Apr 2012;3(2):194-225.

302.Tsang AH, Barclay JL, Oster H. Interactions between endocrine and circadian systems. J Mol Endocrinol. Feb 2014;52(1):R1-16.

303.Burman D. Sleep Disorders: Circadian Rhythm Sleep-Wake Disorders. FP Essent. Sep 2017;460:33-36.

304.Xie Z, Chen F, Li WA, et al. A review of sleep disorders and melatonin. Neurol Res. Jun 2017;39(6):559-565.

305.Auld F, Maschauer EL, Morrison I, Skene DJ, Riha RL. Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Sleep Med Rev. Aug 2017;34:10-22.

306.Zisapel N. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. Br J Pharmacol. Jan 10 2018.

307.Pawlikowski M, Kolomecka M, Wojtczak A, Karasek M. Effects of six months melatonin treatment on sleep quality and serum concentrations of estradiol, cortisol, dehydroepiandrosterone sulfate, and somatomedin C in elderly women. Neuro Endocrinol Lett. Apr 2002;23 Suppl 1:17-19.

308.Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab. Jun 1994;78(6):1360-1367.

309.Alhaj HA, Massey AE, McAllister-Williams RH. Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study. Psychopharmacology (Berl). Nov 2006;188(4):541-551.

310.Liao LY, He YF, Li L, et al. A preliminary review of studies on adaptogens: comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide. Chin Med. 2018;13:57.

311.Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. Aug 2017;1401(1):49-64.

312.Panossian A, Wikman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity. Pharmaceuticals (Basel). Jan 19 2010;3(1):188-224.

313.Lee YJ, Lee YM, Lee CK, Jung JK, Han SB, Hong JT. Therapeutic applications of compounds in the Magnolia family. Pharmacol Ther. May 2011;130(2):157-176.

314.Xu Q, Yi LT, Pan Y, et al. Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia officinalis in stressed rodents. Prog Neuropsychopharmacol Biol Psychiatry. Apr 1 2008;32(3):715-725.

315.Li LF, Lu J, Li XM, et al. Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats. Phytother Res. Aug 2012;26(8):1189-1194.

316.Wang C, Gan D, Wu J, Liao M, Liao X, Ai W. Honokiol Exerts Antidepressant Effects in Rats Exposed to Chronic Unpredictable Mild Stress by Regulating Brain Derived Neurotrophic Factor Level and Hypothalamus-Pituitary-Adrenal Axis Activity. Neurochem Res. Aug 2018;43(8):1519-1528.

317.Cheng J, Dong S, Yi L, Geng D, Liu Q. Magnolol abrogates chronic mild stress-induced depressive-like behaviors by inhibiting neuroinflammation and oxidative stress in the prefrontal cortex of mice. Int Immunopharmacol. Jun 2018;59:61-67.

318.Talbott SM, Talbott JA, Pugh M. Effect of Magnolia officinalis and Phellodendron amurense (Relora(R)) on cortisol and psychological mood state in moderately stressed subjects. J Int Soc Sports Nutr. 2013;10(1):37.

319.Garrison R, Chambliss WG. Effect of a proprietary Magnolia and Phellodendron extract on weight management: a pilot, double-blind, placebo-controlled clinical trial. Altern Ther Health Med. Jan-Feb 2006;12(1):50-54.

320.Kalman DS, Feldman S, Feldman R, Schwartz HI, Krieger DR, Garrison R. Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial. Nutr J. Apr 21 2008;7:11.

321.Cohen MM. Tulsi - Ocimum sanctum: A herb for all reasons. J Ayurveda Integr Med. Oct-Dec 2014;5(4):251-259.

322.Jamshidi N, Cohen MM. The Clinical Efficacy and Safety of Tulsi in Humans: A Systematic Review of the Literature. Evid Based Complement Alternat Med. 2017;2017:9217567.

323.Sampath S, Mahapatra SC, Padhi MM, Sharma R, Talwar A. Holy basil (Ocimum sanctum Linn.) leaf extract enhances specific cognitive parameters in healthy adult volunteers: A placebo controlled study. Indian J Physiol Pharmacol. Jan-Mar 2015;59(1):69-77.

324.Saxena RC, Singh R, Kumar P, et al. Efficacy of an Extract of Ocimum tenuiflorum (OciBest) in the Management of General Stress: A Double-Blind, Placebo-Controlled Study. Evid Based Complement Alternat Med. 2012;2012:894509.

325.Bhattacharyya D, Sur TK, Jana U, Debnath PK. Controlled programmed trial of Ocimum sanctum leaf on generalized anxiety disorders. Nepal Med Coll J. Sep 2008;10(3):176-179.

326.Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):208-213.

327.Yenisetti SC, Manjunath MJ, Muralidhara C. Neuropharmacological Properties of Withania somnifera - Indian Ginseng: An Overview on Experimental Evidence with Emphasis on Clinical Trials and Patents. Recent Pat CNS Drug Discov. 2016;10(2):204-215.

328.Dar PA, Singh LR, Kamal MA, Dar TA. Unique Medicinal Properties of Withania somnifera: Phytochemical Constituents and Protein Component. Curr Pharm Des. 2016;22(5):535-540.

329.Dar NJ, Hamid A, Ahmad M. Pharmacologic overview of Withania somnifera, the Indian Ginseng. Cell Mol Life Sci. Dec 2015;72(23):4445-4460.

330.Pratte MA, Nanavati KB, Young V, Morley CP. An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera). J Altern Complement Med. Dec 2014;20(12):901-908.

331.Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. Jul 2012;34(3):255-262.

332.Choudhary D, Bhattacharyya S, Joshi K. Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial. J Evid Based Complementary Altern Med. Jan 2017;22(1):96-106.

333.Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res. Aug 2013;16(4):313-326.

334.Sheikh N, Ahmad A, Siripurapu KB, Kuchibhotla VK, Singh S, Palit G. Effect of Bacopa monniera on stress induced changes in plasma corticosterone and brain monoamines in rats. J Ethnopharmacol. May 22 2007;111(3):671-676.

335.Liu X, Liu F, Yue R, et al. The antidepressant-like effect of bacopaside I: possible involvement of the oxidative stress system and the noradrenergic system. Pharmacol Biochem Behav. Sep 2013;110:224-230.

336.Kumar SS, Saraswathi P, Vijayaraghavan R. Effect of bacopa monniera on cold stress induced neurodegeneration in hippocampus of wistar rats: a histomorphometric study. J Clin Diagn Res. Jan 2015;9(1):Af05-07.

337.Rai D, Bhatia G, Palit G, Pal R, Singh S, Singh HK. Adaptogenic effect of Bacopa monniera (Brahmi). Pharmacol Biochem Behav. Jul 2003;75(4):823-830.

338.Chowdhuri DK, Parmar D, Kakkar P, Shukla R, Seth PK, Srimal RC. Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytother Res. Nov 2002;16(7):639-645.

339.Banerjee R, Hazra S, Ghosh AK, Mondal AC. Chronic administration of bacopa monniera increases BDNF protein and mRNA expressions: a study in chronic unpredictable stress induced animal model of depression. Psychiatry Investig. Jul 2014;11(3):297-306.

340.Hazra S, Kumar S, Saha GK, Mondal AC. Reversion of BDNF, Akt and CREB in Hippocampus of Chronic Unpredictable Stress Induced Rats: Effects of Phytochemical, Bacopa Monnieri. Psychiatry Investig. Jan 2017;14(1):74-80.

341.Zu X, Zhang M, Li W, et al. Antidepressant-like Effect of Bacopaside I in Mice Exposed to Chronic Unpredictable Mild Stress by Modulating the Hypothalamic-Pituitary-Adrenal Axis Function and Activating BDNF Signaling Pathway. Neurochem Res. Nov 2017;42(11):3233-3244.

342.Kumar S, Mondal AC. Neuroprotective, Neurotrophic and Anti-oxidative Role of Bacopa monnieri on CUS Induced Model of Depression in Rat. Neurochem Res. Nov 2016;41(11):3083-3094.

343.Phulara SC, Shukla V, Tiwari S, Pandey R. Bacopa monnieri promotes longevity in Caenorhabditis elegans under stress conditions. Pharmacogn Mag. Apr-Jun 2015;11(42):410-416.

344.Benson S, Downey LA, Stough C, Wetherell M, Zangara A, Scholey A. An acute, double-blind, placebo-controlled cross-over study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on multitasking stress reactivity and mood. Phytother Res. Apr 2014;28(4):551-559.

345.Calabrese C, Gregory WL, Leo M, Kraemer D, Bone K, Oken B. Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med. Jul 2008;14(6):707-713.

346.Shakeri A, Sahebkar A, Javadi B. Melissa officinalis L. - A review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. Jul 21 2016;188:204-228.

347.Miraj S, Rafieian K, Kiani S. Melissa officinalis L: A Review Study With an Antioxidant Prospective. J Evid Based Complementary Altern Med. Jul 2017;22(3):385-394.

348.Scholey A, Gibbs A, Neale C, et al. Anti-stress effects of lemon balm-containing foods. Nutrients. Oct 30 2014;6(11):4805-4821.

349.Kennedy DO, Little W, Scholey AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med. Jul-Aug 2004;66(4):607-613.

350.Cases J, Ibarra A, Feuillere N, Roller M, Sukkar SG. Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Med J Nutrition Metab. Dec 2011;4(3):211-218.

351.Haybar H, Javid AZ, Haghighizadeh MH, Valizadeh E, Mohaghegh SM, Mohammadzadeh A. The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina. Clin Nutr ESPEN. Aug 2018;26:47-52.

352.Dolatabadi F, Abdolghaffari AH, Farzaei MH, et al. The Protective Effect of Melissa officinalis L. in Visceral Hypersensitivity in Rat Using 2 Models of Acid-induced Colitis and Stress-induced Irritable Bowel Syndrome: A Possible Role of Nitric Oxide Pathway. J Neurogastroenterol Motil. Jul 30 2018;24(3):490-501.

353.Gohari AR, Saeidnia S, Mahmoodabadi MK. An overview on saffron, phytochemicals, and medicinal properties. Pharmacogn Rev. Jan-Jun 2013;7(13):61-66.

354.Shafiee M, Arekhi S, Omranzadeh A, Sahebkar A. Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action. J Affect Disord. Feb 2018;227:330-337.

355.Pitsikas N. Constituents of Saffron (Crocus sativus L.) as Potential Candidates for the Treatment of Anxiety Disorders and Schizophrenia. Molecules. Mar 02 2016;21(3):303.

356.Ghadrdoost B, Vafaei AA, Rashidy-Pour A, et al. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol. Sep 30 2011;667(1-3):222-229.

357.Dastgerdi AH, Radahmadi M, Pourshanazari AA, Dastgerdi HH. Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels. Adv Biomed Res. 2017;6:157.

358.Bandegi AR, Rashidy-Pour A, Vafaei AA, Ghadrdoost B. Protective Effects of Crocus Sativus L. Extract and Crocin against Chronic-Stress Induced Oxidative Damage of Brain, Liver and Kidneys in Rats. Adv Pharm Bull. Dec 2014;4(Suppl 2):493-499.

359.Farkhondeh T, Samarghandian S, Samini F, Sanati AR. Protective Effects of Crocetin on Depression-like Behavior Induced by Immobilization in Rat. CNS Neurol Disord Drug Targets. 2018;17(5):361-369.

360.Kell G, Rao A, Beccaria G, Clayton P, Inarejos-Garcia AM, Prodanov M. affron((R)) a novel saffron extract (Crocus sativus L.) improves mood in healthy adults over 4 weeks in a double-blind, parallel, randomized, placebo-controlled clinical trial. Complement Ther Med. Aug 2017;33:58-64.

361.Xu W, Choi HK, Huang L. State of Panax ginseng Research: A Global Analysis. Molecules. Sep 11 2017;22(9).

362.Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res. Oct 2017;41(4):435-443.

363.Kim KH, Lee D, Lee HL, Kim CE, Jung K, Kang KS. Beneficial effects of Panax ginseng for the treatment and prevention of neurodegenerative diseases: past findings and future directions. J Ginseng Res. Jul 2018;42(3):239-247.

364.Kim JH. Pharmacological and medical applications of Panax ginseng and ginsenosides: a review for use in cardiovascular diseases. J Ginseng Res. Jul 2018;42(3):264-269.

365.Lee YM, Yoon H, Park HM, Song BC, Yeum KJ. Implications of red Panax ginseng in oxidative stress associated chronic diseases. J Ginseng Res. Apr 2017;41(2):113-119.

366.Flanagan SD, DuPont WH, Caldwell LK, et al. The Effects of a Korean Ginseng, GINST15, on Hypo-Pituitary-Adrenal and Oxidative Activity Induced by Intense Work Stress. J Med Food. Jan 2018;21(1):104-112.

367.Huang L, Zhao H, Huang B, Zheng C, Peng W, Qin L. Acanthopanax senticosus: review of botany, chemistry and pharmacology. Pharmazie. Feb 2011;66(2):83-97.

368.Ishaque S, Shamseer L, Bukutu C, Vohra S. Rhodiola rosea for physical and mental fatigue: a systematic review. BMC Complement Altern Med. May 29 2012;12:70.

369.Li Y, Pham V, Bui M, et al. Rhodiola rosea L.: an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention. Curr Pharmacol Rep. Dec 2017;3(6):384-395.

370.Chiang HM, Chen HC, Wu CS, Wu PY, Wen KC. Rhodiola plants: Chemistry and biological activity. J Food Drug Anal. Sep 2015;23(3):359-369.

371.Kasper S, Dienel A. Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms. Neuropsychiatr Dis Treat. 2017;13:889-898.

372.Lekomtseva Y, Zhukova I, Wacker A. Rhodiola rosea in Subjects with Prolonged or Chronic Fatigue Symptoms: Results of an Open-Label Clinical Trial. Complement Med Res. 2017;24(1):46-52.

373.Cropley M, Banks AP, Boyle J. The Effects of Rhodiola rosea L. Extract on Anxiety, Stress, Cognition and Other Mood Symptoms. Phytother Res. Dec 2015;29(12):1934-1939.

374.Amsterdam JD, Panossian AG. Rhodiola rosea L. as a putative botanical antidepressant. Phytomedicine. Jun 15 2016;23(7):770-783.

375.Concerto C, Infortuna C, Muscatello MRA, et al. Exploring the effect of adaptogenic Rhodiola Rosea extract on neuroplasticity in humans. Complement Ther Med. Dec 2018;41:141-146.

376.Variya BC, Bakrania AK, Patel SS. Emblica officinalis (Amla): A review for its phytochemistry, ethnomedicinal uses and medicinal potentials with respect to molecular mechanisms. Pharmacol Res. Sep 2016;111:180-200.

377.Tahir I, Khan MR, Shah NA, Aftab M. Evaluation of phytochemicals, antioxidant activity and amelioration of pulmonary fibrosis with Phyllanthus emblica leaves. BMC Complement Altern Med. Oct 24 2016;16(1):406.

378.Fatima N, Pingali U, Pilli R. Evaluation of Phyllanthus emblica extract on cold pressor induced cardiovascular changes in healthy human subjects. Pharmacognosy Res. Jan 2014;6(1):29-35.

379.Bhattacharya A, Ghosal S, Bhattacharya SK. Antioxidant activity of tannoid principles of Emblica officinalis (amla) in chronic stress induced changes in rat brain. Indian J Exp Biol. Sep 2000;38(9):877-880.

380.Arun S, Burawat J, Yannasithinon S, Sukhorum W, Limpongsa A, Iamsaard S. Phyllanthus emblica leaf extract ameliorates testicular damage in rats with chronic stress. J Zhejiang Univ Sci B. Dec. 2018;19(12):948-959.

381.Dwivedi V, Lakhotia SC. Ayurvedic Amalaki Rasayana promotes improved stress tolerance and thus has anti-aging effects in Drosophila melanogaster. J Biosci. Dec 2016;41(4):697-711.

382.Szopa A, Ekiert R, Ekiert H. Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies. Phytochem Rev. 2017;16(2):195-218.

383.Zhang M, Xu L, Yang H. Schisandra chinensis Fructus and Its Active Ingredients as Promising Resources for the Treatment of Neurological Diseases. Int J Mol Sci. Jul 6 2018;19(7).

384.Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S. An overview of neuroprotective and cognitive enhancement properties of lignans from Schisandra chinensis. Biomed Pharmacother. Jan 2018;97:958-968.

385.Chen WW, He RR, Li YF, Li SB, Tsoi B, Kurihara H. Pharmacological studies on the anxiolytic effect of standardized Schisandra lignans extract on restraint-stressed mice. Phytomedicine. Oct 15 2011;18(13):1144-1147.

386.Xia N, Li J, Wang H, Wang J, Wang Y. Schisandra chinensis and Rhodiola rosea exert an anti-stress effect on the HPA axis and reduce hypothalamic c-Fos expression in rats subjected to repeated stress. Exp Ther Med. Jan 2016;11(1):353-359.

387.Yan T, Xu M, Wan S, et al. Schisandra chinensis produces the antidepressant-like effects in repeated corticosterone-induced mice via the BDNF/TrkB/CREB signaling pathway. Psychiatry Res. Sep 30 2016;243:135-142.

388.Zhou X, Gong Z, Su Y, Lin J, Tang K. Cordyceps fungi: natural products, pharmacological functions and developmental products. J Pharm Pharmacol. Mar 2009;61(3):279-291.

389.Olatunji OJ, Tang J, Tola A, Auberon F, Oluwaniyi O, Ouyang Z. The genus Cordyceps: An extensive review of its traditional uses, phytochemistry and pharmacology. Fitoterapia. Sep 2018;129:293-316.

390.Liu Y, Wang J, Wang W, Zhang H, Zhang X, Han C. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis. Evid Based Complement Alternat Med. 2015;2015:575063.

391.Tianzhu Z, Shihai Y, Juan D. Antidepressant-like effects of cordycepin in a mice model of chronic unpredictable mild stress. Evid Based Complement Alternat Med. 2014;2014:438506.

392.Rossi P, Buonocore D, Altobelli E, et al. Improving Training Condition Assessment in Endurance Cyclists: Effects of Ganoderma lucidum and Ophiocordyceps sinensis Dietary Supplementation. Evid Based Complement Alternat Med. 2014;2014:979613.

393.Javidi H, Yadollahie M. Post-traumatic Stress Disorder. Int J Occup Environ Med. 2012;3(1):2-9.

394.Strada EA. Psychosocial Issues and Bereavement. Primary care. 2019;46(3):373-386.

395.Cohen GJ, Weitzman CC. Helping Children and Families Deal With Divorce and Separation. Pediatrics. 2016;138(6).

396.Linden M, Rotter M. Unemployment and embitterment in contrast to general psychological distress. Work. 2019;62(1):133-138.

397.King J, O'Neill B, Ramsay P, et al. Identifying patients' support needs following critical illness: a scoping review of the qualitative literature. Crit Care. 2019;23(1):187.

398.Torales J, O'Higgins M, Castaldelli-Maia JM, Ventriglio A. The outbreak of COVID-19 coronavirus and its impact on global mental health. Int J Soc Psychiatry. 2020:20764020915212.

399.Chew QH, Wei KC, Vasoo S, Chua HC, Sim K. Narrative synthesis of psychological and coping responses towards emerging infectious disease outbreaks in the general population: practical considerations for the COVID-19 pandemic. Singapore medical journal. 2020.

400.Lai J, Ma S, Wang Y, et al. Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019. JAMA Netw Open. 2020;3(3):e203976.

401.Express Scripts. America's State of Mind Report. https://www.express-scripts.com/corporate/americas-state-of-mind-report. Published 2020. Accessed.

402.Wilder-Smith A, Freedman DO. Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak. Journal of travel medicine. 2020;27(2).

403.Xiao H, Zhang Y, Kong D, Li S, Yang N. Social Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Disease 2019 (COVID-19) Outbreak in January 2020 in China. Med Sci Monit. 2020;26:e923921.

404.Xiao H, Zhang Y, Kong D, Li S, Yang N. The Effects of Social Support on Sleep Quality of Medical Staff Treating Patients with Coronavirus Disease 2019 (COVID-19) in January and February 2020 in China. Med Sci Monit. 2020;26:e923549.

405.Cohen S, Janicki-Deverts D, Turner RB, Doyle WJ. Does hugging provide stress-buffering social support A study of susceptibility to upper respiratory infection and illness. Psychol Sci. 2015;26(2):135-147.

406.Cohen S, Tyrrell DA, Smith AP. Psychological stress and susceptibility to the common cold. The New England journal of medicine. 1991;325(9):606-612.

407.Takkouche B, Regueira C, Gestal-Otero JJ. A cohort study of stress and the common cold. Epidemiology (Cambridge, Mass). 2001;12(3):345-349.

408.Cohen S. Keynote Presentation at the Eight International Congress of Behavioral Medicine: the Pittsburgh common cold studies: psychosocial predictors of susceptibility to respiratory infectious illness. International journal of behavioral medicine. 2005;12(3):123-131.

409.Cohen S, Janicki-Deverts D, Doyle WJ, et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci U S A. 2012;109(16):5995-5999.

410.Cohen S, Doyle WJ, Skoner DP. Psychological stress, cytokine production, and severity of upper respiratory illness. Psychosomatic medicine. 1999;61(2):175-180.

411.Janicki-Deverts D, Cohen S, Turner RB, Doyle WJ. Basal salivary cortisol secretion and susceptibility to upper respiratory infection. Brain Behav Immun. 2016;53:255-261.

412.Fung SY, Yuen KS, Ye ZW, Chan CP, Jin DY. A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses. Emerg Microbes Infect. 2020;9(1):558-570.

413.Altena E, Baglioni C, Espie CA, et al. Dealing with sleep problems during home confinement due to the COVID-19 outbreak: practical recommendations from a task force of the European CBT-I Academy. J Sleep Res. 2020.

414.Liu N, Zhang F, Wei C, et al. Prevalence and predictors of PTSS during COVID-19 outbreak in China hardest-hit areas: Gender differences matter. Psychiatry research. 2020;287:112921.

415.Brooks SK, Webster RK, Smith LE, et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020;395(10227):912-920.

416.Wang C, Pan R, Wan X, et al. Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China. International journal of environmental research and public health. 2020;17(5).

417.Cao W, Fang Z, Hou G, et al. The psychological impact of the COVID-19 epidemic on college students in China. Psychiatry research. 2020;287:112934.

418.Depoux A, Martin S, Karafillakis E, Bsd RP, Wilder-Smith A, Larson H. The pandemic of social media panic travels faster than the COVID-19 outbreak. Journal of travel medicine. 2020.

419.Dong M, Zheng J. Letter to the editor: Headline stress disorder caused by Netnews during the outbreak of COVID-19. Health expectations : an international journal of public participation in health care and health policy. 2020;23(2):259-260.

420.Shimizu K. 2019-nCoV, fake news, and racism. Lancet. 2020;395(10225):685-686.

421.Bastani P, Bahrami MA. COVID-19 Related Misinformation on Social Media: A Qualitative Study from Iran. J Med Internet Res. 2020.

422.Garfin DR, Silver RC, Holman EA. The novel coronavirus (COVID-2019) outbreak: Amplification of public health consequences by media exposure. Health Psychol. 2020.

423.Merchant RM, Lurie N. Social Media and Emergency Preparedness in Response to Novel Coronavirus. JAMA. 2020.

424.Gaffey AE, Bergeman CS, Clark LA, Wirth MM. Aging and the HPA axis: Stress and resilience in older adults. Neuroscience and biobehavioral reviews. 2016;68:928-945.

425.Dantzer R, Cohen S, Russo SJ, Dinan TG. Resilience and immunity. Brain Behav Immun. 2018;74:28-42.

426.Ditzen B, Heinrichs M. Psychobiology of social support: the social dimension of stress buffering. Restor Neurol Neurosci. 2014;32(1):149-162.

427.Luthar SS, Kumar NL, Benoit R. Toward fostering resilience on a large scale: Connecting communities of caregivers. Dev Psychopathol. 2019;31(5):1813-1825.

428.Ruisoto P, Contador I, Fernandez-Calvo B, et al. Mediating effect of social support on the relationship between resilience and burden in caregivers of people with dementia. Arch Gerontol Geriatr. 2020;86:103952.

429.Lee JS. Perceived social support functions as a resilience in buffering the impact of trauma exposure on PTSD symptoms via intrusive rumination and entrapment in firefighters. PLoS One. 2019;14(8):e0220454.

430.Motreff Y, Baubet T, Pirard P, et al. Factors associated with PTSD and partial PTSD among first responders following the Paris terror attacks in November 2015. Journal of psychiatric research. 2020;121:143-150.

431.Zhang J, Guo F, Chen ZY, He HW, Long Y, Li Q. [Relationship between social support, resilience, self-esteem and post-traumatic stress disorder in intensive care unit nurses]. Zhonghua yi xue za zhi. 2020;100(1):32-36.

432.Blake L, Bray L, Carter B. "It's a lifeline": Generating a sense of social connectedness through befriending parents of disabled children or children with additional need. Patient Educ Couns. 2019;102(12):2279-2285.

433.Park SK, Seong RK, Kim JA, et al. Oligonol promotes anti-aging pathways via modulation of SIRT1-AMPK-Autophagy Pathway. Nutrition research and practice. 2016;10(1):3-10.

434.Lee JB, Shin YO, Min YK, Yang HM. The effect of Oligonol intake on cortisol and related cytokines in healthy young men. Nutrition research and practice. 2010;4(3):203-207.

435.Shin Y-O, Lee J-B, Min Y-K, Yang H-M. Effect of oligonol intake on cortisol and cytokines, and body temperature after leg immersion into hot water. Food Science and Biotechnology. 2011;20(3):659-663.

436.Kaszkin-Bettag M, Ventskovskiy BM, Kravchenko A, et al. The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women. Menopause (New York, NY). 2007;14(2):270-283.

437.Heger M, Ventskovskiy BM, Borzenko I, et al. Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial. Menopause (New York, NY). 2006;13(5):744-759.

438.Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007;74(1):39-45.

439.Kocaadam B, Sanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr. 2017;57(13):2889-2895.

440.Naqvi F, Saleem S, Naqvi F, et al. Curcumin lessens unpredictable chronic mild stress-induced depression and memory deficits by modulating oxidative stress and cholinergic activity. Pakistan journal of pharmaceutical sciences. 2019;32(4(Supplementary)):1893-1900.

441.Aubry AV, Khandaker H, Ravenelle R, et al. A diet enriched with curcumin promotes resilience to chronic social defeat stress. Neuropsychopharmacology. 2019;44(4):733-742.

442.Lee B, Lee H. Systemic Administration of Curcumin Affect Anxiety-Related Behaviors in a Rat Model of Posttraumatic Stress Disorder via Activation of Serotonergic Systems. Evidence-based complementary and alternative medicine : eCAM. 2018;2018:9041309.

443.Shen JD, Wei Y, Li YJ, Qiao JY, Li YC. Curcumin reverses the depressive-like behavior and insulin resistance induced by chronic mild stress. Metabolic brain disease. 2017;32(4):1163-1172.

444.Haider S, Naqvi F, Batool Z, et al. Pretreatment with curcumin attenuates anxiety while strengthens memory performance after one short stress experience in male rats. Brain research bulletin. 2015;115:1-8.

445.Fan C, Song Q, Wang P, et al. Curcumin Protects Against Chronic Stress-induced Dysregulation of Neuroplasticity and Depression-like Behaviors via Suppressing IL-1beta Pathway in Rats. Neuroscience. 2018;392:92-106.

446.Choi GY, Kim HB, Hwang ES, et al. Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats. Mediators Inflamm. 2017;2017:6280925.

447.Liu D, Wang Z, Gao Z, et al. Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress. Behavioural brain research. 2014;271:116-121.

448.Fusar-Poli L, Vozza L, Gabbiadini A, et al. Curcumin for depression: a meta-analysis. Crit Rev Food Sci Nutr. 2019:1-11.

449.Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical Use of Curcumin in Depression: A Meta-Analysis. Journal of the American Medical Directors Association. 2017;18(6):503-508.

450.Al-Karawi D, Al Mamoori DA, Tayyar Y. The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials. Phytother Res. 2016;30(2):175-183.

451.Pandaran Sudheeran S, Jacob D, Natinga Mulakal J, et al. Safety, Tolerance, and Enhanced Efficacy of a Bioavailable Formulation of Curcumin With Fenugreek Dietary Fiber on Occupational Stress: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. Journal of clinical psychopharmacology. 2016;36(3):236-243.

452.Asadi S, Gholami MS, Siassi F, Qorbani M, Sotoudeh G. Beneficial effects of nano-curcumin supplement on depression and anxiety in diabetic patients with peripheral neuropathy: A randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2020;34(4):896-903.

453.Kanchanatawan B, Tangwongchai S, Sughondhabhirom A, et al. Add-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study. Neurotoxicity research. 2018;33(3):621-633.

454.Sciberras JN, Galloway SD, Fenech A, et al. The effect of turmeric (Curcumin) supplementation on cytokine and inflammatory marker responses following 2 hours of endurance cycling. Journal of the International Society of Sports Nutrition. 2015;12(1):5.