Inflammation-driven brain and gut barrier dysfunction in stress and mood disorders.
Inflammation-driven brain and gut barrier dysfunction in stress and mood disorders.
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DOI：
10.1111/ejn.15239
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发表时间：
2022-05
影响因子：
3.4
通讯作者：
Menard, Caroline
中科院分区：
文献类型：
--
作者：
Doney, Ellen;Cadoret, Alice;Dion-Albert, Laurence;Lebel, Manon;Menard, Caroline
情绪的调节通常只与大脑有关。然而，有证据表明，外围系统也参与了情绪，压力脆弱性与弹性，以及与情绪相关的记忆编码。现代社会中，压力和情绪障碍（如重度抑郁症、双相情感障碍和创伤后应激障碍）的患病率正在增加。不幸的是，30%-50%的人对目前可用的治疗反应不佳，这突出表明需要进一步研究与情绪相关的生物学，以获得可能导致创新疗法的机制见解。在这里，我们概述了使用动物模型发现的情绪调节和应激反应中涉及的炎症相关机制。如果有临床研究，我们将讨论这些发现的转化价值，包括局限性。抑郁症和适应不良应激反应的神经免疫机制受到越来越多的关注，因此，第一部分集中在应激和情绪障碍中的大脑和循环细胞因子的炎症和失调。接下来，最近的研究支持炎症驱动的血脑和肠道屏障在情绪调节和情绪中的泄漏。应激诱导的炎症加重使这些屏障脆弱，这些屏障通过丧失完整性和改变生物学而变得超渗透。在肠道水平，这可能与生态失调，微生物群落的不平衡以及肠-脑轴的改变有关，肠-脑轴是产生情绪相关神经递质5-羟色胺的核心。新的治疗方法，如抗炎药，速效抗抑郁药氯胺酮和益生菌可以直接作用于本文所述的机制，改善情绪障碍相关的神经病学。生物标记物的发现一直是精神病学中具有挑战性的探索，我们通过列出值得进一步研究的有希望的目标来结束。应激和情绪障碍中炎症驱动的脑和肠道屏障功能障碍情绪障碍，如创伤后应激障碍（PTSD），重度抑郁症（MDD）和双相情感障碍（BD），与治疗抵抗和复发率高有关。越来越多的证据将血脑屏障（BBB）和肠道屏障渗漏与情绪障碍中报告的负面情绪症状联系起来，可能是通过应激诱导的炎症，尽管具体的生物学机制仍有待阐明。靶向血脑屏障和肠道屏障通透性的新治疗方法可能有助于弥合治疗反应中的差距。
Regulation of emotions is generally associated exclusively with the brain. However, there is evidence that peripheral systems are also involved in mood, stress vulnerability vs. resilience, and emotion‐related memory encoding. Prevalence of stress and mood disorders such as major depression, bipolar disorder, and post‐traumatic stress disorder is increasing in our modern societies. Unfortunately, 30%–50% of individuals respond poorly to currently available treatments highlighting the need to further investigate emotion‐related biology to gain mechanistic insights that could lead to innovative therapies. Here, we provide an overview of inflammation‐related mechanisms involved in mood regulation and stress responses discovered using animal models. If clinical studies are available, we discuss translational value of these findings including limitations. Neuroimmune mechanisms of depression and maladaptive stress responses have been receiving increasing attention, and thus, the first part is centered on inflammation and dysregulation of brain and circulating cytokines in stress and mood disorders. Next, recent studies supporting a role for inflammation‐driven leakiness of the blood–brain and gut barriers in emotion regulation and mood are highlighted. Stress‐induced exacerbated inflammation fragilizes these barriers which become hyperpermeable through loss of integrity and altered biology. At the gut level, this could be associated with dysbiosis, an imbalance in microbial communities, and alteration of the gut–brain axis which is central to production of mood‐related neurotransmitter serotonin. Novel therapeutic approaches such as anti‐inflammatory drugs, the fast‐acting antidepressant ketamine, and probiotics could directly act on the mechanisms described here improving mood disorder‐associated symptomatology. Discovery of biomarkers has been a challenging quest in psychiatry, and we end by listing promising targets worth further investigation. Inflammation‐driven brain and gut barrier dysfunction in stress and mood disorders. Mood disorders, such as post‐traumatic stress disorder (PTSD), major depressive disorder (MDD), and bipolar disorder (BD), are associated with high rates of treatment resistance and relapse. Increasing evidence links blood–brain barrier (BBB) and gut barrier leakiness to negative emotional symptoms reported in mood disorders, possibly through stress‐induced inflammation, although specific biological mechanisms remain to be elucidated. Novel therapeutic approaches targeting BBB and gut barrier permeability could contribute to bridging the gap in treatment response.
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氯胺酮和快速作用的抗抑郁药：介绍新的神经生物学的窗口，用于情绪障碍疗法。
影响因子：
10.5
作者：
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影响因子：
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DOI：
10.1080/13651501.2017.1306081
发表时间：
2017-01-01
影响因子：
3
作者：
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影响因子：
5.6
作者：
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DOI：
10.1093/ijnp/pyv103
发表时间：
2015-09-12
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Ambrée O;Bergink V;Grosse L;Alferink J;Drexhage HA;Rothermundt M;Arolt V;Birkenhäger TK
通讯作者：
Birkenhäger TK