D-cycloserine augmented single-session CBT for panic disorder

D-环丝氨酸增强单次 CBT 治疗恐慌症

• 批准号: MR/J011878/1
• 负责人: Catherine Harmer
• 金额: $ 27.25万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ011878%2F1
• 关键词: cycloserine; augmented; single; session; CBT

All of us are familiar with occasional feelings of panic, but for at least 5 out of every 100 of us, this becomes problematic and can be clinically diagnosed as panic disorder. It is characterised by intense and sudden physical symptoms, such as extreme palpitations or dizziness and is usually accompanied by a fear of death or dying. Half of the patients also develop agoraphobia, where certain situations are avoided for fear of experiencing further attacks, and a patient may become effectively house bound. Treatment of panic disorder is usually with a psychological intervention such as cognitive-behavioural therapy (CBT) or with a drug treatment like a serotonin reuptake inhibitor (SSRI). These treatments are effective, but for CBT, the courses are long and cost-intensive and access to treatment is difficult. For the drug treatment, symptoms usually return when the patient stops their SSRI medication, and for both interventions there is a subgroup of patients who do not get better at all.To improve treatments, it is important to identify how they are working and why both psychological and drug treatments can have similar effects. Our recent work suggests that both CBT and drug treatments used for panic disorder affect the way in which the brain processes threatening information and that such effects can be seen very early on in treatment before the patient notices subjectively that anything has changed. Moreover, these early changes on emotional processing are related to how well the patient responds to treatment in the longer term. Interventions which boost these early effects on emotional processing may therefore improve the efficacy of treatment for panic disorder.This proposal aims to test the effects of a single session CBT approach, which we have shown has clear effects on the response to threatening information, with a pharmacological treatment thought to improve the generalisation and durability of these effects. Research in rodents suggests that the antibiotic d-cycloserine (DCS) improves learning and memory by stimulating a mechanism in the brain which plays a core role in our ability to make new connections and retain information. This study will establish the potential of the novel combination of the single-session CBT treatment with the pharmacological agent DCS as a stand-alone treatment for panic disorder with agoraphobia, and it will determine the basic mechanisms of such an augmentation effect. In particular, we will investigate i) whether the combination treatment improves the impact of single-session CBT on clinical symptom severity, with greater response during a 4-weeks follow-up period, ii) whether such an augmentation effect remains stable over a 6-months follow-up period, and iii) the cognitive and neural mechanisms underlying DCS augmented single-session CBT. The findings will have crucial implications for the development of a new and cost-economic treatment with the potential for low-threshold access for a higher number of patients with anxiety disorders.

我们都熟悉偶尔会有恐慌的感觉，但每100个人中至少有5个人会有这种感觉，这会成为问题，可以在临床上诊断为恐慌症。它的特点是剧烈和突然的身体症状，如极端心悸或头晕，通常伴随着对死亡或死亡的恐惧。一半的患者还会患上广场恐惧症，这种情况下会避免某些情况，因为担心会遇到进一步的攻击，患者可能会变得有效地呆在家里。恐慌症的治疗通常是通过心理干预，如认知行为疗法(CBT)或药物治疗，如5-羟色胺再摄取抑制剂(SSRI)。这些治疗方法是有效的，但对于CBT来说，疗程长，成本高，而且很难获得治疗。对于药物治疗，当患者停止服用SSRI药物时，症状通常会重新出现，对于这两种干预措施，都有一小部分患者根本没有好转。为了改进治疗，重要的是确定他们是如何工作的，以及为什么心理治疗和药物治疗都有类似的效果。我们最近的工作表明，用于治疗恐慌症的CBT和药物治疗都会影响大脑处理威胁信息的方式，并且在患者主观上注意到事情发生变化之前，这种影响就可以在治疗的很早就看到。此外，这些情绪处理的早期变化与患者对治疗的长期反应有多好有关。因此，加强情绪处理的这些早期影响的干预措施可能会改善恐慌症的治疗效果。这项建议旨在测试单次CBT方法的效果，我们已经证明，这种方法在对威胁信息的反应方面具有明显的效果，药物治疗的思想是提高这些影响的概括性和持久性。对啮齿动物的研究表明，抗生素d-环丝氨酸(Dcs)通过刺激大脑中的一种机制来改善学习和记忆，这种机制在我们建立新的联系和记忆信息的能力中发挥着核心作用。这项研究将确定单次CBT治疗与药理学药物DCS作为单独治疗惊恐障碍伴广场恐怖症的新组合的潜力，并将确定这种增强效应的基本机制。特别是，我们将调查i)联合治疗是否改善了单次CBT对临床症状严重程度的影响，在4周的随访期内有更大的反应，ii)这种增强效果是否在6个月的随访期内保持稳定，以及iii)DCS增强单次CBT背后的认知和神经机制。这一发现将对开发一种新的、成本低廉的治疗方法具有至关重要的意义，这种治疗方法有可能为更多的焦虑症患者提供低门槛治疗。

项目成果

Investigating d-cycloserine as a potential pharmacological enhancer of an emotional bias learning procedure.

研究 d-环丝氨酸作为情绪偏见学习程序的潜在药理学增强剂。

• DOI: 10.1177/0269881118754679
• 发表时间: 2018
• 期刊: Journal of psychopharmacology (Oxford, England)
• 作者: Woud ML

Neurocognitive mechanisms of d-cycloserine augmented single-session exposure therapy for anxiety

d-环丝氨酸增强单次暴露疗法治疗焦虑的神经认知机制

• DOI: 10.1101/615757
• 发表时间: 2019
• 作者: Reinecke A

Neurocognitive processes in d-cycloserine augmented single-session exposure therapy for anxiety: A randomized placebo-controlled trial.

d-环丝氨酸增强单次暴露疗法治疗焦虑的神经认知过程：一项随机安慰剂对照试验。

• DOI: 10.1016/j.brat.2020.103607
• 发表时间: 2020
• 期刊: Behaviour research and therapy
• 影响因子: 4.1
• 作者: Reinecke A

The NMDA receptor partial agonist d-cycloserine does not enhance motor learning.

• DOI: 10.1177/0269881116658988
• 发表时间: 2016-10
• 期刊: Journal of psychopharmacology (Oxford, England)
• 作者: Günthner J;Scholl J;Favaron E;Harmer CJ;Johansen-Berg H;Reinecke A
• 通讯作者: Reinecke A

A role beyond learning for NMDA receptors in reward-based decision-making-a pharmacological study using d-cycloserine.

• DOI: 10.1038/npp.2014.144
• 发表时间: 2014-11
• 期刊: NEUROPSYCHOPHARMACOLOGY
• 影响因子: 7.6
• 作者: Scholl, Jacqueline;Guenthner, Jan;Kolling, Nils;Favaron, Elisa;Rushworth, Matthew F. S.;Harmer, Catherine J.;Reinecke, Andrea
• 通讯作者: Reinecke, Andrea