Steimer Thierry, Python Agathe, Schulz Pierre E, Aubry Jean-Michel
Laboratoire de recherches-Unité de Psychopharmacologie clinique (APSI), 2, ch. du Petit-Bel-Air, CH-1225 Chêne-Bourg (Suisse), Switzerland.
Psychoneuroendocrinology. 2007 Jun;32(5):575-9. doi: 10.1016/j.psyneuen.2007.03.012.
The hypothalamo-pituitary-adrenal (HPA) axis is hyperactive in major depressive disorder (MDD), and baseline cortisol levels are usually elevated in MDD patients, with alterations of the circadian hormone secretion pattern. The dexamethasone (DEX) suppression test (DST) has been extensively applied to diagnose a dysregulation of the HPA axis in MDD, but it has only a limited sensitivity to, and specificity for, depression. The DEX/CRH test, which combines the DST with a corticotropin-releasing hormone (CRH) challenge, has proved more reliable to show HPA axis dysfunction in MDD. We have applied these two tests to a putative model of vulnerability to depression in rodents, the Roman high-(RHA) and low-(RLA) Avoidance rat lines. As compared to RHA, RLA rats are behaviorally inhibited, they show an exaggerated response of the HPA axis to stress, and are more prone to develop depressive-like features when exposed to chronic stress. Our results show that (a) there were no significant differences in circadian plasma corticosterone (CORT) levels and/or secretion patterns between the two lines; (b) in the DST test, CORT was suppressed to the same extent in RHA and RLA rats; and c) in the DEX/CRH test, areas-under-the-curve (AUCs) and CORT delta (peak minus baseline) responses were significantly larger in RLA rats. One possible interpretation of these data is that an increased response to CRH could be a trait marker (or endophenotype) for depression, whereas alterations of circadian glucocorticoid secretion patterns and non-suppression of the daily glucocorticoid rise by dexamethasone could be state markers, i.e. features that are only present during depressive episodes.
下丘脑 - 垂体 - 肾上腺（HPA）轴在重度抑郁症（MDD）中处于亢进状态，MDD患者的皮质醇基线水平通常升高，昼夜激素分泌模式也会发生改变。地塞米松（DEX）抑制试验（DST）已被广泛应用于诊断MDD中HPA轴的失调，但它对抑郁症的敏感性和特异性都有限。DEX/促肾上腺皮质激素释放激素（CRH）试验将DST与促肾上腺皮质激素释放激素（CRH）激发试验相结合，已被证明在显示MDD中HPA轴功能障碍方面更可靠。我们已将这两种试验应用于啮齿动物中一种假定的抑郁症易感性模型，即罗马高回避（RHA）和低回避（RLA）大鼠品系。与RHA相比，RLA大鼠在行为上受到抑制，它们的HPA轴对应激的反应更为夸张，并且在暴露于慢性应激时更容易出现类似抑郁的特征。我们的结果表明：（a）两品系之间的昼夜血浆皮质酮（CORT）水平和/或分泌模式没有显著差异；（b）在DST试验中，RHA和RLA大鼠的CORT被抑制到相同程度；（c）在DEX/CRH试验中，RLA大鼠的曲线下面积（AUCs）和CORT变化量（峰值减去基线）反应显著更大。这些数据的一种可能解释是，对CRH反应的增加可能是抑郁症的一种特质标记（或内表型），而昼夜糖皮质激素分泌模式的改变以及地塞米松未能抑制每日糖皮质激素升高可能是状态标记，即仅在抑郁发作期间出现的特征。
