Department of Psychiatry (GGZ inGeest), Amsterdam UMC (location VUmc), Vrije University, Amsterdam Public Health and Amsterdam Neuroscience Research Institutes, Amsterdam, the Netherlands; Department of Anatomy and Neurosciences, Amsterdam UMC (location VUmc), Vrije University, Amsterdam, the Netherlands.
Department of Psychiatry (GGZ inGeest), Amsterdam UMC (location VUmc), Vrije University, Amsterdam Public Health and Amsterdam Neuroscience Research Institutes, Amsterdam, the Netherlands.
J Affect Disord. 2021 Mar 15;283:139-146. doi: 10.1016/j.jad.2021.01.051. Epub 2021 Jan 27.
Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary-adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)). Suchdysregulationshave rarely beensimultaneously examined across different stress systems.
In the Netherlands Study of Depression and Anxiety (n=2789), we investigated whether current or remitted depressive and/or anxiety disorders (based on the CIDI semi-structured interview), including specific symptom profiles, were associated with separate markers and cumulative indexes of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), immune system (C-reactive protein, interleukin-6, tumor necrosis factor-α), and ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period).
Depressive andanxiety disorderswere significantlyassociated with changes in three biological stress systemsincluding HPA-axis hyperactivity, increased inflammatory activity, and a higher ANS tone, particularly for integrative and cumulative indexes of these stress systems (pFDR <.05) vs. controls. The strongest associations were seen with current disorders andcumulative indexes of the HPA-axis (β=.124, pFDR=.001), the immune system (β =.057, pFDR=.032), and total cumulative index across stress systems (β=.102, pFDR=.004). Atypical, energy-related depression severity was linked to immune system markers (pFDR<0.001), melancholic depression severity to HPA-axis markers (pFDR=.032), and anxiety arousal severity to both HPA-axis and immune system markers (pFDR<0.05). Findings were partially explained by poorer lifestyle, more chronic diseases,or (especially for ANS-function) antidepressant use.
Cross-sectional analyses limit examination of temporal associations.
Patients withdepressive and anxiety disorders showed consistent dysregulation across biological stress systems, particularly for current episodes.To understand stress system functionality in affective disorders, an integrated approach capturing cumulative stress indices within and across biological stress systems is important.
情感障碍涉及主要生物应激系统（下丘脑-垂体-肾上腺（HPA）轴、免疫系统、自主神经系统（ANS））的失调。这些失调很少在不同的应激系统中同时进行检查。
在荷兰抑郁和焦虑研究（n=2789）中，我们调查了当前或缓解的抑郁和/或焦虑障碍（基于 CIDI 半结构式访谈），包括特定的症状特征，是否与 HPA 轴（皮质醇觉醒反应、傍晚皮质醇、地塞米松抑制试验皮质醇）、免疫系统（C 反应蛋白、白细胞介素-6、肿瘤坏死因子-α）和 ANS（心率、呼吸窦性心律失常、射前间期）的单独标志物和累积指数相关。
抑郁和焦虑障碍与包括 HPA 轴活性增加、炎症活性增加和 ANS 张力增加在内的三个生物应激系统的变化显著相关，特别是对于这些应激系统的综合和累积指数（pFDR<0.05）与对照组相比。与当前障碍和 HPA 轴（β=0.124，pFDR=0.001）、免疫系统（β=0.057，pFDR=0.032）和总应激系统累积指数（β=0.102，pFDR=0.004）的累积指数的关联最强。非典型、与能量相关的抑郁严重程度与免疫系统标志物相关（pFDR<0.001），忧郁性抑郁严重程度与 HPA 轴标志物相关（pFDR=0.032），焦虑唤醒严重程度与 HPA 轴和免疫系统标志物均相关（pFDR<0.05）。这些发现部分可以通过较差的生活方式、更多的慢性疾病或（特别是对于 ANS 功能）抗抑郁药物的使用来解释。
横断面分析限制了对时间关联的检查。
患有抑郁和焦虑障碍的患者表现出跨生物应激系统的一致失调，特别是对于当前发作。为了理解情感障碍中的应激系统功能，重要的是采用一种综合方法来捕获生物应激系统内和跨系统的累积应激指数。
