社会压力，炎症和抑郁症

StephenW

www.natap.org


Social Stress, Inflammation & Depression

from Jules: we are dealing wit an epidemic in HIV, its called Aging & HIV. with over 50% now older than 50 years old & an expected 50% over 60 soon, along with severe comorbidities & polypharmacy & disability in significant members of aging HIV+ - yet, there remains no concerted effort by federal US officials to even discuss the problem in an organized way never mind strategizing solutions. Severe depression along with isolation mobility limitations smong older aging HIV+ is one of the serious problems. Increasingly doctors are putting all these people on anti depression medications, but that is not the answer. Is that ok, to just put these patients on anti-depressants. The aging HIV problem will get worse, morbidity & mortality will worsen suite ideation & substance abuse will worsen, housing & long term care issues will worsen. It is time for federal officials and other stakeholders to begin discussing this problem, which by the way impacts both marginalized patient populations as well as others, but as usual marginalized patient populations are impacted worse, have less services often and capacity to navigate the healthcare system.
Social stress induces neurovascular pathology promoting depression
Nature Neuroscience Nov 13 2017

Abstract
Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood–brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5.
downregulation was sufficient to induce depression-like behaviors following subthreshold social stress whereas chronic antidepressant treatment rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or mice injected with adeno-associated virus expressing shRNA against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across the BBB and depression.
Main

Major depressive disorder (MDD) is the leading cause of worldwide disability and the most prevalent mood disorder1,2. The prevalence of MDD is two- to threefold higher in patients with cardiovascular disease and, conversely, MDD is associated with an ∼80% increased risk of cardiovascular morbidity and mortality1,3,4,5. Chronic inflammation and sustained increases in circulating pro-inflammatory cytokines have been associated with atherosclerotic plaque formation, progression and rupture, likely contributing to the pathogenesis of cardiovascular disease and heart failure6. Concomitantly, clinical studies report higher levels of circulating pro-inflammatory cytokines in patients with MDD, a pattern that has been replicated in preclinical animal models of depression1,7,8,9,10. Individual differences in the peripheral immune system and modulation of cytokine release, notably IL-6, are associated with susceptibility versus resilience to chronic social stress11. Chronic stress mobilizes the innate immune system and stimulates enhanced proliferation and release of inflammatory monocytes and neutrophils into the bloodstream12,13.
It has been hypothesized that peripheral myeloid cells or pro-inflammatory cytokines can diffuse into the brain of stressed individuals as a result of stress-induced neurovascular damage and increased BBB permeability7,14,15,16,17,18,19. Indeed, a clinical study reported an altered cerebrospinal fluid to serum ratio of peripheral markers in depressed patients, suggesting that BBB integrity is compromised20. However, the possible link between BBB permeability, stress vulnerability and depression is still controversial21. The BBB is formed by endothelial cells sealed by tight junction proteins, pericytes and astrocytes, and serves to prevent potentially harmful signals in the blood from entering the brain. Here we evaluate the effect of chronic social defeat stress (CSDS), a mouse model of depression, on BBB-related gene expression and define a role for the tight junction protein claudin 5 (Cldn5) in the establishment of depression-like behaviors and MDD. Cldn5 is a major cell adhesion molecule in endothelial cells22, and loss of Cldn5 has been shown to promote loosening of the BBB and increased permeability23. Our study thus characterizes and functionally interrogates the neurovascular pathology associated with social stress vulnerability.

StephenW

www.natap.org


社会压力，炎症和抑郁症

来自朱尔斯：我们正在处理艾滋病毒的流行病，称为老龄化和艾滋病毒。现在50岁以上的人超过50％，60岁以上的人超过60岁，预计有50％，伴随着老龄化艾滋病毒重要成员的严重合并症和多种药物及残疾，但是，美国联邦官员甚至没有协调一致地讨论这个问题有组织的方式不要介意战略性的解决方案。严重的抑郁症伴随着隔离移动性的限制，更老的艾滋病病毒感染是严重的问题之一。越来越多的医生正在把所有这些人都用在抗抑郁药物上，但这不是答案。没关系，只是把这些病人放在抗抑郁药上。艾滋病的老化问题会越来越严重，发病率和死亡率会恶化套房的想法，物质滥用将会恶化，住房和长期护理问题将恶化。现在是联邦官员和其他利益相关者开始讨论这个问题的时候了，这个问题既影响边缘化的患者人群，也影响到其他人，但像往常一样，边缘化的患者群体受到的影响更为严重，经常服务的次数也减少， 。
社会压力诱导神经血管病理学促进抑郁症
自然神经科学2017年11月13日

抽象
研究表明，高度外周炎症有助于抑郁症的发病机制。我们研究了慢性社交失败压力（一种抑郁症小鼠模型）对血脑屏障（BBB）通透性和外周免疫信号的浸润的影响。我们发现内皮细胞紧密连接蛋白claudin-5（Cldn5）的表达减少和伏核（NAc）压力敏感但不具有弹性的小鼠的异常血管形态。抑郁症患者的NAc中CLDN5的表达也下降。 CLDN5。
下调足以诱导亚阈值社会压力下的抑郁样行为，而慢性抗抑郁药治疗挽救了Cldn5的损失并提高了复原力。在注射表达针对Cldn5的shRNA的腺伴随病毒的应激敏感或小鼠的NAc中BBB完整性降低引起外周细胞因子白细胞介素-6（IL-6）渗入脑实质并随后表达抑郁样行为。这些研究结果表明慢性社会压力通过损失紧密连接蛋白Cldn5改变BBB完整性，促进外周IL-6通过BBB和抑郁。
主要

严重抑郁症（MDD）是世界性残疾的首要原因，也是最普遍的心境障碍1,2。 MDD患病率在心血管疾病患者中高出2-3倍，相反，MDD与心血管疾病和死亡风险增加约80％相关[1,3,4,5]。循环促炎症细胞因子的慢性炎症和持续增加与动脉粥样硬化斑块的形成，进展和破裂有关，可能导致心血管疾病和心力衰竭的发病机制6。同时，临床研究报道了MDD患者循环促炎性细胞因子的水平较高，这种模式已经在抑郁症的临床前动物模型中被复制[1,7,8,9,10]。外周免疫系统的个体差异和细胞因子释放的调节，特别是IL-6，与慢性社会压力的易感性和恢复能力相关11。慢性应激可以调动先天免疫系统，刺激炎症单核细胞和嗜中性粒细胞进入血液的增殖和释放[12,13]。
据推测外周髓样细胞或促炎性细胞因子可以通过应激诱导的神经血管损伤和增加血脑屏障通透性而扩散到受压个体的大脑中[7,14,15,16,17,18,19]。事实上，一项临床研究报告抑郁症患者的外周标记物的脑脊液与血清比例改变，提示BBB完整性受损20。然而，BBB通透性，压力易感性和抑郁症之间的可能联系仍然存在争议21。 BBB由紧密连接蛋白，周细胞和星形胶质细胞密封的内皮细胞形成，并且用于防止血液中可能有害的信号进入大脑。在这里，我们评估慢性社会失败压力（CSDS）对抑郁症小鼠模型对BBB相关基因表达的影响，并确定紧密连接蛋白claudin 5（Cldn5）在建立抑郁样行为和MDD中的作用。 Cldn5是内皮细胞中的一种主要的细胞粘附分子[22]，Cldn5的缺失已被证明可促进BBB的松弛和增加通透性[23]。因此，我们的研究表征和功能审问与社会压力脆弱性相关的神经血管病理学。

neilhbver

所以乙肝跟抑郁症有因果关系？j

StephenW

回复 neilhbver 的帖子

如果因为乙肝有精神压力.

neilhbver

回复 StephenW 的帖子

研究表明，高度外周炎症有助于抑郁症的发病机制。
可以理解成炎症会促进抑郁症发作？

StephenW

回复 neilhbver 的帖子

我的理解:
是的，非常复杂, 是一个假设.
精神压力 -> 影响先天免疫系统 ->刺激细胞因子的产生 -->穿过血脑屏障 -> 抑郁症发作?