Department of Psychiatry, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Department of Psychiatry, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria.
Curr Top Med Chem. 2018;18(19):1621-1640. doi: 10.2174/1568026618666181115101625.
Generalized Anxiety Disorder (GAD) commonly co-occurs with mood disorders, especially Major Depressive Disorder (MDD) and bipolar disorder (BD), which are accompanied by activated neuro-immune and neuro-oxidative pathways. The aim of this narrative review is to review the phenomenological similarities and dissimilarities and the shared pathways between GAD and mood disorders. We searched PubMed, Scopus, and Google Scholar for articles published in English from 1980 to present. GAD and mood disorders, either MDD or BD, show some phenomenological overlaps and a high degree of comorbidity, especially between GAD and MDD. Both GAD and mood disorders are also frequently comorbid with other anxiety disorders, substance use disorders and medical conditions, including cardio- vascular disorder (CVD). Mood disorders have a worse prognosis when GAD is present. GAD and mood disorders are associated with female sex and may partly share genetic variants of risk. Moreover, both GAD and mood disorders frequently share similar environmental risks factors including Early Life Time Trauma (ELT) and Psychological Stressors in Adulthood (PSA). Increased nitro-oxidative stress and lipid peroxidation coupled to lowered lipid-associated antioxidant defenses are evident in GAD, MDD and type I bipolar patients. Patients with comorbid GAD and MDD show significantly higher nitro- oxidative biomarkers as compared with patients presenting with either GAD or MDD as well as patients with BD with or without co-occurring GAD. Activated immune-inflammatory processes characterized by increased levels of CRP and pro-inflammatory cytokines are other shared pathways that underpin GAD and mood disorders. Moreover, these pathways may explain comorbidities with medical disorders including CVD. Aberrations in HPA-axis, GABA and glutamate neurotransmission, NMDA and mu opioid-receptors and neuroimaging fields have yielded more inconsistent findings. In conclusion, here we propose a new model explaining GAD and the comorbidity between GAD and mood disorders. Common triggers such as ELT/PSA may underpin GAD and its comorbidity with mood disorders via activated neuro-oxidative, neuro-nitrosative and neuro-immune pathways.
广泛性焦虑障碍（GAD）常与心境障碍共病，尤其是重性抑郁障碍（MDD）和双相障碍（BD），这些疾病伴有激活的神经免疫和神经氧化途径。本叙述性综述的目的是回顾 GAD 与心境障碍之间的表型相似性和差异性以及共享途径。我们在 PubMed、Scopus 和 Google Scholar 上搜索了自 1980 年至今发表的英文文章。GAD 和心境障碍，无论是 MDD 还是 BD，都表现出一些表型上的重叠和高度的共病性，尤其是 GAD 和 MDD 之间。GAD 和心境障碍也常与其他焦虑障碍、物质使用障碍和包括心血管疾病（CVD）在内的躯体疾病共病。当 GAD 存在时，心境障碍的预后更差。GAD 和心境障碍与女性性别有关，并且可能部分共享风险的遗传变异。此外，GAD 和心境障碍常共享相似的环境风险因素，包括早期生活创伤（ELT）和成年期心理应激源（PSA）。GAD、MDD 和 1 型双相患者中存在明显的硝基氧化应激和脂质过氧化增加，同时伴有脂质相关抗氧化防御降低。与仅患有 GAD 或 MDD 的患者以及患有 BD 且无共病 GAD 的患者相比，共病 GAD 和 MDD 的患者表现出明显更高的硝基氧化生物标志物。激活的免疫炎症过程的特征是 CRP 和促炎细胞因子水平升高，这也是 GAD 和心境障碍的另一个共享途径。此外，这些途径可能解释了与包括 CVD 在内的躯体疾病的共病关系。HPA 轴、GABA 和谷氨酸神经递质、NMDA 和μ阿片受体以及神经影像学领域的改变得出了更不一致的发现。总之，在这里我们提出了一个新的模型来解释 GAD 以及 GAD 与心境障碍的共病关系。共同的触发因素，如 ELT/PSA，可能通过激活的神经氧化、神经硝化和神经免疫途径，为 GAD 及其与心境障碍的共病关系提供基础。
