Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Psychoneuroendocrinology. 2012 Jul;37(7):892-902. doi: 10.1016/j.psyneuen.2011.10.005. Epub 2011 Nov 17.
Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity has been observed in (recurrent) major depressive disorder (MDD), although inconsistently and mainly cross-sectional. Longitudinal studies clarifying state-trait issues are lacking. We aimed to determine whether HPA-axis (hyper)activity in recurrent MDD is: (I) reflecting a persistent trait; (II) influenced by depressive state; (III) associated with stress or previous episodes; (IV) associated with recurrence; and (V) influenced by cognitive therapy.
We included 187 remitted highly recurrent MDD-patients (mean number of previous episodes: 6.3), participating in a randomized-controlled-trial investigating the preventive effect of additional cognitive therapy on recurrence. In an add-on two-staged patient-control and prospective-cohort design, we first cross-sectionally compared patients' salivary morning and evening cortisol concentrations with 72 age- and sex-matched controls, and subsequently longitudinally followed-up the patients with repeated measures after three months and two years.
Patients had higher cortisol concentrations than controls (p<.001), which did not change by MDD-episodes during follow-up. HPA-axis activity had no relation with daily hassles or childhood life events. Cortisol concentrations were lower in patients with more previous episodes (p=.047), but not associated with recurrence(s) during follow-up. Finally, randomly assigned cognitive therapy at study-entry enhanced cortisol declines over the day throughout the two-year follow-up (p=.052).
Our results indicate that remitted recurrent MDD-patients have a persistent trait of increased cortisol concentrations, irrespective of stress. In combination with our finding that patients' cortisol concentrations do not change during new MDD-episodes (and thus not represent epiphenomenal or state-effects), our results support that hypercortisolemia fulfills the state-independence criterion for an endophenotype for recurrent depression.
尽管存在不一致性且主要是横断面研究，但在（复发性）重度抑郁症（MDD）中观察到下丘脑-垂体-肾上腺（HPA）轴活性亢进。缺乏阐明状态-特质问题的纵向研究。我们旨在确定复发性 MDD 中 HPA 轴（过度）活性是否：（I）反映持久的特质；（II）受抑郁状态影响；（III）与应激或既往发作有关；（IV）与复发有关；以及（V）受认知疗法影响。
我们纳入了 187 名缓解后反复发作的重度抑郁症患者（既往发作次数的平均值：6.3），参与了一项随机对照试验，研究附加认知疗法对复发的预防作用。在附加的两阶段患者对照和前瞻性队列设计中，我们首先将患者的唾液晨晚皮质醇浓度与 72 名年龄和性别匹配的对照进行横断面比较，随后对患者进行了三个月和两年的重复测量纵向随访。
与对照组相比，患者的皮质醇浓度更高（p<.001），且在随访期间不因 MDD 发作而改变。HPA 轴活性与日常烦恼或儿童生活事件无关。皮质醇浓度与既往发作次数较多的患者相关（p=.047），但与随访期间的复发无关。最后，在研究开始时随机分配认知疗法可增强患者在整个两年随访期间的日间皮质醇下降（p=.052）。
我们的结果表明，缓解后反复发作的 MDD 患者具有持续的皮质醇浓度升高的特质，与应激无关。结合我们的发现，患者的皮质醇浓度在新的 MDD 发作期间不会改变（因此不能代表偶发或状态效应），我们的结果支持高皮质醇血症符合复发性抑郁症的状态独立性表型标准。
