Effects of increased noradrenergic activity by yohimbine administration on learning and attention in patients with major depression disorder

育亨宾给药增加去甲肾上腺素能活性对重度抑郁症患者学习和注意力的影响

基本信息

项目摘要

Stress plays a major role in the development and maintenance of major depression disorder (MDD). Indeed, various studies demonstrated maladaptive changes in physiological stress regulation systems of MDD patients, i.e. in the hypothalamus-pituitary-adrenal (HPA) axis and the locus coeruleus-noradrenergic (LC-NA) system. On a central level, changes of the LC-NA system have been demonstrated. Several studies could show changes of the adrenoreceptor responsiveness (up-regulation of alpha2-adrenergic receptors) in MDD patients. This seems to be the case especially in MDD patients with early life traumata. Comparable to the HPA axis, the LC-NA system influences not only the physiological stress response, but has also central influence with effects on cognitive functions. Indeed, NA effects on cognitive functions such as attention, learning and memory have been demonstrated in healthy individuals. In summary, NA seems to have enhancing effects on memory consolidation. Even though deficits in cognitive domains such as attention and memory are core symptoms of MDD, the relationship of the noradrenergic system and memory processes has rarely been investigated so far. Therefore, our research group investigated in a first study the influence of noradrenergic stimulation via administration of the alpha2-receptor blocker yohimbine on different memory functions. There,, we found an improvement of memory consolidation that was even more pronounced in MDD patients compared to healthy controls. Additionally, we found associations of yohimbine triggered consolidation improvements to early life traumata.In this project, we aim to investigate for the first time, if noradrenergic stimulation via administration of the alpha2-receptor blocker yohimbine has also more pronounced effects in MDD patients compared to healthy controls for a) learning and b) attention processes. Therefore, we will examine a) attention processes using an emotional variant of the Dot-Probe-task with a special focus on the depressive negativity bias and b) acquisition and extinction processes using a fear conditioning paradigm. Additionally, we will investigate the influence of early life traumata on these relationships. Thus, we plan to investigate MDD patients with and without early life traumata.For these reasons, we plan to investigate 40 MDD patients (20 with/ 20 without early life traumata) and 40 healthy controls (20 with/ 20 without early life traumata; matched for age, sex and educational status) in a double-blind, placebo controlled, repeated measures design.Results of this study will improve our understanding of cognitive deficits and the role of alpha2-adrenergic system in MDD patients, and thus support the development of new therapeutic strategies by considering these relations.
压力在抑郁症的发展和维持中起着重要作用。事实上,各种研究表明MDD患者的生理应激调节系统(即下丘脑-垂体-肾上腺(HPA)轴和蓝斑-去甲肾上腺素能(LC-NA)系统)存在适应不良变化。在中央一级,LC-NA系统的变化已经得到证明。几项研究可能显示MDD患者肾上腺素受体反应性(α 2-肾上腺素能受体上调)的变化。这似乎是特别是在早期生活创伤的MDD患者的情况。与HPA轴相比,LC-NA系统不仅影响生理应激反应,而且对认知功能也有重要影响。事实上,NA对认知功能如注意力、学习和记忆的影响已经在健康个体中得到证实。总之,NA似乎对记忆巩固有增强作用。尽管注意力和记忆等认知领域的缺陷是MDD的核心症状,但迄今为止,去甲肾上腺素能系统和记忆过程的关系很少被研究。因此,我们的研究小组在第一项研究中调查了通过α 2受体阻滞剂育亨宾对不同记忆功能的去甲肾上腺素能刺激的影响。在那里,我们发现与健康对照组相比,MDD患者的记忆巩固改善更为明显。此外,我们发现育亨宾引发的巩固改善早期生活traumata.In这个项目中,我们的目的是调查第一次,如果去甲肾上腺素刺激通过管理的α 2受体阻滞剂育亨宾也有更显着的效果,在MDD患者与健康对照组相比,a)学习和B)注意力的过程。因此,我们将检查a)注意过程使用情绪变体的点探针任务,特别关注抑郁性消极偏见和B)收购和灭绝过程使用恐惧条件反射范式。此外,我们将调查早期生活创伤对这些关系的影响。因此,我们计划对40例伴有和不伴有早期生活创伤的MDD患者进行调查(20例有/ 20例无早期生活创伤)和40例健康对照(20例有/ 20例无早期生活创伤;年龄、性别和教育状况匹配)在一个双盲、安慰剂对照,重复测量设计。本研究的结果将提高我们对MDD患者认知缺陷和α 2-肾上腺素能系统作用的理解,从而通过考虑这些关系支持新的治疗策略的开发。

项目成果

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Attentional bias in individuals with depression and adverse childhood experiences: influence of the noradrenergic system?
  • DOI:
    10.1007/s00213-021-05969-7
  • 发表时间:
    2021-12
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Kuehl LK;Deuter CE;Nowacki J;Ueberrueck L;Wingenfeld K;Otte C
  • 通讯作者:
    Otte C
Enhanced noradrenergic activity by yohimbine and differential fear conditioning in patients with major depression with and without adverse childhood experiences
育亨宾增强去甲肾上腺素能活性和有或没有不良童年经历的重度抑郁症患者的差异性恐惧调节
Telomere length in individuals with and without major depression and adverse childhood experiences
有或没有重度抑郁症和不良童年经历的个体的端粒长度
  • DOI:
    10.1016/j.psyneuen.2022.105762
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    de Punder;Deuter;Martens;. . . Entringer
  • 通讯作者:
    . . . Entringer
Inflammatory Measures in Depressed Patients With and Without a History of Adverse Childhood Experiences
  • DOI:
    10.3389/fpsyt.2018.00610
  • 发表时间:
    2018-11-27
  • 期刊:
  • 影响因子:
    4.7
  • 作者:
    de Punder, Karin;Entringer, Sonja;Kuehl, Linn K.
  • 通讯作者:
    Kuehl, Linn K.
Noradrenergic activation induced by yohimbine decreases interoceptive accuracy in healthy individuals with childhood adversity
育亨宾诱导的去甲肾上腺素能激活降低了患有童年逆境的健康个体的内感受准确性
  • DOI:
    10.1017/s0954579420001613
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Schulz;Deuter;Breden;Vögele;Wingenfeld
  • 通讯作者:
    Wingenfeld
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Professorin Dr. Linn Kristina Kühl其他文献

Professorin Dr. Linn Kristina Kühl的其他文献

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