Mood disorders like major depression and bipolar disorder (BD) are among the most prevalent forms of mental illness. Current knowledge of the neurobiology and pathophysiology of these disorders is still modest and clear biological markers are still missing. Thus, a better understanding of the underlying pathophysiological mechanisms to identify potential therapeutic targets is a prerequisite for the design of new drugs as well as to develop biomarkers that help in a more accurate and earlier diagnosis. Multiple pieces of evidence including genetic and neuro-imaging studies suggest that mood disorders are associated with abnormalities in endoplasmic-reticulum (ER)-related stress responses, mitochondrial function and calcium signalling. Furthermore, deregulation of the innate immune response has been described in patients diagnosed with mood disorders, including depression and BD. These disease-related events are associated with functions localized to a subdomain of the ER, known as Mitochondria-Associated Membranes (MAMs), which are lipid rafts-like domains that connect mitochondria and ER, both physically and biochemically. This review will outline the current understanding of the role of mitochondria and ER dysfunction under pathological brain conditions particularly in major depressive disorder (MDD) and BD that support the hypothesis that MAMs can act in these mood disorders as the link connecting ER-related stress response and mitochondrial impairment, as well as a mechanisms behind sterile inflammation arising from deregulation of innate immune responses. The role of MAMs in the pathophysiology of these pathologies and its potential relevance as a potential therapeutic target will be discussed.

中文翻译：

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情绪障碍中的线粒体，内质网和先天性免疫功能障碍：线粒体相关膜（MAM）是否起作用？

情绪障碍，例如重性抑郁和双相情感障碍（BD），是最普遍的精神疾病形式。这些疾病的神经生物学和病理生理学的当前知识仍然很少，并且仍然缺少清晰的生物学标记。因此，更好地了解潜在的病理生理机制以识别潜在的治疗靶点是设计新药以及开发有助于更准确，更早诊断的生物标志物的前提。包括基因和神经影像学研究在内的多项证据表明，情绪障碍与内质网（ER）相关的应激反应，线粒体功能和钙信号传导异常有关。此外，已经在诊断患有情绪障碍（包括抑郁症和BD）的患者中描述了先天免疫反应的失调。这些与疾病相关的事件与定位于ER子域（称为线粒体相关膜（MAMs））的功能相关，后者是在物理和生物化学上连接线粒体和ER的类脂筏样结构域。这篇综述将概述目前对病理性脑部疾病中线粒体和内质网功能障碍的作用的理解，特别是在重度抑郁症（MDD）和BD中，这支持了MAM可以在这些情绪障碍中作为连接内质网相关应激反应的联系的假设和线粒体损伤，以及由先天免疫反应失调引起的无菌炎症背后的机制。