Virginia Commonwealth University School of Nursing, Richmond, VA, USA.
J Neurosci Nurs. 2011 Feb;43(1):17-28. doi: 10.1097/jnn.0b013e3182029859.
More than 51,000 individuals are diagnosed with a primary brain tumor in the United States each year, and for those with the most common type of malignant tumor, an astrocytoma, almost 75% will die within 5 years of diagnosis. Although surgery, radiation, and chemotherapy have improved length of survival, mortality remains high, which underscores the need to understand how other factors affect the disease trajectory. Several recent studies have shown that depressive symptoms are independently associated with reduced quality of life and survival time after controlling for other variables in patients with an astrocytoma. Thus, depressive symptoms represent a significant risk factor for adverse outcomes in this patient population. A growing body of evidence indicates that depressive symptoms are linked to underlying biological phenomena, particularly inflammatory activation modulated through increased peripheral levels of proinflammatory cytokines. Recent research has shown that neoplastic astrocytes respond to elevated proinflammatory cytokine levels by secreting immune mediators within the central nervous system, including cytokines and glial fibrillary acidic protein that promote astrogliosis and angiogenesis and may increase tumor growth and metastasis. However, because these biological factors have not as yet been measured in conjunction with depressive symptoms in these patients, little is known about the interactions that potentially influence the treatment trajectory. To guide future research and to provide a deeper understanding of the factors that may influence depressive symptoms and length of survival in patients with an astrocytoma, a review of the literature was undertaken. Publications over the past 10 years were analyzed to examine the theoretical models and measures of depressive symptoms used in previous research. Although numerous studies have documented the relationship between depression and reduced length of survival, there were several methodological concerns identified, and there were no studies that included biological variables. Yet, research in the basic sciences provides compelling evidence of specific neuroendocrine-immune interactions orchestrated by astrocytes that can cause depressive symptoms and alter the tumor microenvironment so that standard treatments are not as effective. These findings support the need for clinically based research so that we can begin to understand the potentially modifiable biobehavioral mechanisms underlying depressive symptoms in patients with an astrocytoma. Grounded in the biobehavioral research paradigm of psychoneuroimmunology, a novel research program is presented that may provide a new level of understanding regarding the high prevalence of depressive symptoms in patients with an astrocytoma and lead to new treatment strategies, with possible implications for improved symptom management and quality of life in patients with brain tumors.
每年，美国有超过 51000 人被诊断出患有原发性脑肿瘤，对于最常见的恶性肿瘤——星形细胞瘤患者来说，近 75%的患者在诊断后 5 年内会死亡。尽管手术、放疗和化疗已经提高了生存率，但死亡率仍然很高，这突显了需要了解其他因素如何影响疾病进程。最近的几项研究表明，在控制星形细胞瘤患者的其他变量后，抑郁症状与生活质量下降和生存时间缩短独立相关。因此，抑郁症状是该患者群体不良预后的一个重要危险因素。越来越多的证据表明，抑郁症状与潜在的生物学现象有关，特别是通过外周促炎细胞因子水平升高而调节的炎症激活。最近的研究表明，肿瘤星形胶质细胞对升高的促炎细胞因子水平做出反应，在中枢神经系统内分泌免疫介质，包括细胞因子和神经胶质纤维酸性蛋白，促进星形胶质增生和血管生成，可能增加肿瘤生长和转移。然而，由于这些生物学因素尚未与这些患者的抑郁症状一起测量，因此对于潜在影响治疗轨迹的相互作用知之甚少。为了指导未来的研究，并更深入地了解可能影响星形细胞瘤患者抑郁症状和生存时间的因素，对文献进行了回顾。分析了过去 10 年的出版物，以检查以前研究中使用的抑郁症状的理论模型和测量方法。尽管许多研究都记录了抑郁与生存时间缩短之间的关系，但也发现了几个方法学问题，而且没有研究包括生物学变量。然而，基础科学的研究提供了令人信服的证据，表明星形胶质细胞协调的特定神经内分泌-免疫相互作用可导致抑郁症状，并改变肿瘤微环境，使标准治疗效果不佳。这些发现支持开展基于临床的研究，以便我们能够开始了解星形细胞瘤患者抑郁症状的潜在可改变的生物行为机制。基于心理神经免疫学的生物行为研究范式，提出了一个新的研究计划，这可能为理解星形细胞瘤患者中抑郁症状的高发生率提供一个新的水平，并为新的治疗策略提供依据，这可能对脑肿瘤患者的症状管理和生活质量的提高产生影响。
