Department of Psychiatry and Institute of Neuroscience, Adelaide and Meath Hospital incorporating the National Children's Hospital and St James' s Hospital, University Dublin, Trinity College, Dublin, Ireland.
Transl Psychiatry. 2012 Mar 13;2(3):e88. doi: 10.1038/tp.2012.14.
Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.
神经可塑性可能在重性抑郁障碍（MDD）的病理生理学中起核心作用，这一概念得到了实验研究的支持，这些研究发现，皮质醇分泌过多和/或炎症细胞因子过度产生会损害海马神经元的可塑性和神经发生。本研究的目的是研究糖皮质激素和炎症系统的变化如何影响 MDD 患者的海马体积。采用结构神经影像学（海马和杏仁核）、外周炎症蛋白白细胞介素（IL）-6 和 C 反应蛋白（CRP）、糖皮质激素受体（GR）mRNA 表达以及糖皮质激素诱导基因（糖皮质激素诱导基因 Leucin Zipper（GILZ）和糖皮质激素诱导激酶-1（SGK-1））的多模态方法，对 40 名 MDD 患者和 43 名健康对照者（HC）进行了研究。与 HC 相比，MDD 患者的海马体积较小，炎症蛋白 IL-6 和 CRP 水平较高。儿童期虐待与 CRP 增加有关。MDD 患者中，糖皮质激素诱导基因 GILZ 或 SGK-1 表达较少的患者海马体积较小。回归分析显示，GILZ 和 SGK-1 mRNA 表达与海马体积呈正相关，IL-6 浓度与海马体积呈负相关。这些发现表明，儿童期虐待、外周炎症和糖皮质激素标志物以及海马体积是 MDD 病理生理学中的相互关联的因素。糖皮质激素诱导基因 GILZ 和 SGK-1 可能是与 MDD 等疾病相关的海马体积变化的有前途的候选标志物。需要进一步的研究来探索这种血液生物标志物的可能临床用途，例如用于诊断或预测治疗反应。
