Lang Undine E, Borgwardt Stefan
University Hospital of Basel, Department of Psychiatry and Psychotherapy, Basel, Switzerland.
Cell Physiol Biochem. 2013;31(6):761-77. doi: 10.1159/000350094. Epub 2013 May 31.
Depression is a multicausal disorder and has been associated with the risk to develop cancer, dementia, diabetes, epilepsy and stroke. As a metabolic disorder depression has been associated with obesity, diabetes, insulin sensitivity, neuropeptide Y, glucose regulation, poor glycemic control, glucagone-like peptide-1, cholezystokinin, ghrelin, leptin, the endocannabinoid system, insulin-like growth factor and gastrin-releasing peptide. As a cardiovascular disease a close relationship exists between depression and blood pressure, heart rate, norepinephrine, sympathetic tone, vascular resistance, blood viscosity, plasma volume, intima thickness and atherosclerosis. Additionally blood coagulation, fibrinolysis, D-dimers, plasminogen activator inhibitor-1 protein, platelet activation, VEGF, plasma nitric oxide and its synthase are changed in depressed patients. As an endocrinological and stress disorder depression has been connected with the concentration of free T4, TSH, CRH, arginine vasopressin, corticotrophin, corticosteroid release and ACTH. Depression as an inflammatory disorder is mediated by pro-inflammatory cytokines, interleukin-1, interleukin-6, TNF-alpha, soluble interleukin-2 receptors, interferon-alpha, interleukin 8, interleukin-10, hs-CRP, acute phase proteins, haptoglobin, toll like receptor 4, interleukin-1beta, mammalian target of rapamycin pathway, substance P, cyclooxygenase-2, prostaglandin-E2, lipid peroxidation levels and acid sphingomyelinase. Nutritional factors might influence depression risk, i.e. the consumption of folate, omega-3 fatty acids, monounsaturated fatty acids, olive oil, fish, fruits, vegetables, nuts, legumes, vitamin B6 and vitamin B12. The neurodegenerative hypothesis of depression explains decreased hippocampal volumes in depressed patients and changes of neurotrophic support by BDNF, erythropoietin, GDNF, FGF-2, NT3, NGF and growth hormone. In this context, a fast neuroprotective and antidepressant effect has also been observed by ketamine, which acts via the glutamatergic system. Hence, GABA, AMPA, EAAT, NMDA- and metabotropic glutamate receptors (mGluR1 to mGluR8) have gained interest in depression recently. Alternative, causative or also easy available treatment strategies beyond serotonin and noradrenaline reuptake inhibition might be a major topic of future psychiatric care. In this review, an attempt is made to overview concepts of the disease and search for perspectives on antidepressant treatment strategies beyond approved medications.
抑郁症是一种多因素导致的疾病，与患癌症、痴呆症、糖尿病、癫痫和中风的风险相关。作为一种代谢紊乱疾病，抑郁症与肥胖、糖尿病、胰岛素敏感性、神经肽Y、葡萄糖调节、血糖控制不佳、胰高血糖素样肽-1、胆囊收缩素、胃饥饿素、瘦素、内源性大麻素系统、胰岛素样生长因子和胃泌素释放肽有关。作为一种心血管疾病，抑郁症与血压、心率、去甲肾上腺素、交感神经张力、血管阻力、血液粘度、血浆容量、内膜厚度和动脉粥样硬化之间存在密切关系。此外，抑郁症患者的血液凝固、纤维蛋白溶解、D-二聚体、纤溶酶原激活物抑制剂-1蛋白、血小板活化、血管内皮生长因子、血浆一氧化氮及其合酶也会发生变化。作为一种内分泌和应激障碍，抑郁症与游离甲状腺素、促甲状腺激素、促肾上腺皮质激素释放激素、精氨酸加压素、促肾上腺皮质激素、皮质类固醇释放和促肾上腺皮质激素的浓度有关。抑郁症作为一种炎症性疾病，由促炎细胞因子、白细胞介素-1、白细胞介素-6、肿瘤坏死因子-α、可溶性白细胞介素-2受体、干扰素-α、白细胞介素8、白细胞介素-10、高敏C反应蛋白、急性期蛋白、触珠蛋白、Toll样受体4、白细胞介素-1β、雷帕霉素哺乳动物靶点通路、P物质、环氧化酶-2、前列腺素-E2、脂质过氧化水平和酸性鞘磷脂酶介导。营养因素可能会影响抑郁症风险，即叶酸、ω-3脂肪酸、单不饱和脂肪酸、橄榄油、鱼类、水果、蔬菜、坚果、豆类、维生素B6和维生素B12的摄入量。抑郁症的神经退行性假说解释了抑郁症患者海马体积减小以及脑源性神经营养因子、促红细胞生成素、胶质细胞源性神经营养因子、成纤维细胞生长因子-2、神经营养因子-3、神经生长因子和生长激素对神经营养支持的改变。在这种情况下，氯胺酮也观察到了快速的神经保护和抗抑郁作用，它通过谷氨酸能系统发挥作用。因此，γ-氨基丁酸、α-氨基-3-羟基-5-甲基-异恶唑丙酸、兴奋性氨基酸转运体、N-甲基-D-天冬氨酸和代谢型谷氨酸受体（mGluR1至mGluR8）最近在抑郁症研究中受到关注。除了5-羟色胺和去甲肾上腺素再摄取抑制之外，替代性、因果性或易于获得的治疗策略可能是未来精神科护理的一个主要课题。在这篇综述中，我们试图概述该疾病的概念，并寻找除已批准药物之外的抗抑郁治疗策略的前景。
