Belvederi Murri Martino, Pariante Carmine, Mondelli Valeria, Masotti Mattia, Atti Anna Rita, Mellacqua Zefiro, Antonioli Marco, Ghio Lucio, Menchetti Marco, Zanetidou Stamatula, Innamorati Marco, Amore Mario
Institute of Psychiatry, Department of Psychological Medicine, King's College London, London, UK; Department of Neurosciences Division of Psychiatry, University of Parma, Parma, Italy.
Institute of Psychiatry, Department of Psychological Medicine, King's College London, London, UK.
Psychoneuroendocrinology. 2014 Mar;41:46-62. doi: 10.1016/j.psyneuen.2013.12.004. Epub 2013 Dec 17.
One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic-pituitary-adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We found 20 studies, for a total of 43 comparisons on different indices of HPA axis functioning. Depression had a significant effect (Hedges' g) on basal cortisol levels measured in the morning (0.89), afternoon (0.83) and night (1.39), but a smaller effect on cortisol measured continuously (0.51). The effect of depression was even higher on post-dexamethasone cortisol levels (3.22), whereas it was non-significant on morning ACTH and CRH levels. Subgroup analyses indicated that various methodological and clinical factors can influence the study results. Overall, older participants suffering from depression show a high degree of dysregulation of HPA axis activity, with differences compared with younger adults. This might depend on several mechanisms, including physical illnesses, alterations in the CNS and immune-endocrinological alterations. Further studies are needed to clarify the implications of altered HPA axis activity in older patients suffering from depression. Novel pharmacological approaches might be effective in targeting this pathophysiological feature, thus improving the clinical outcomes.
抑郁症生物学领域最一致的发现之一是下丘脑 - 垂体 - 肾上腺（HPA）轴的活动改变。然而，关于这个问题的数据从未以老年人群为重点进行过研究。在此，我们基于对60岁以上抑郁症患者与健康对照者的皮质醇、促肾上腺皮质激素（ACTH）和促肾上腺皮质激素释放激素（CRH）水平进行研究的文献，进行了一项系统综述和荟萃分析。我们找到了20项研究，共对HPA轴功能的不同指标进行了43次比较。抑郁症对早晨（0.89）、下午（0.83）和夜间（1.39）测量的基础皮质醇水平有显著影响（Hedges' g），但对连续测量的皮质醇影响较小（0.51）。抑郁症对服用地塞米松后的皮质醇水平影响更大（3.22），而对早晨ACTH和CRH水平无显著影响。亚组分析表明，各种方法学和临床因素会影响研究结果。总体而言，老年抑郁症患者表现出HPA轴活动高度失调，与年轻成年人存在差异。这可能取决于多种机制，包括躯体疾病、中枢神经系统改变和免疫 - 内分泌改变。需要进一步研究来阐明HPA轴活动改变在老年抑郁症患者中的意义。新的药理学方法可能对针对这一病理生理特征有效，从而改善临床结局。
