Defining, understanding, and treating lack of motivation in schizophrenia

精神分裂症缺乏动力的定义、理解和治疗

• 批准号: MR/W029987/1
• 负责人: Emilio Fernandez-Egea
• 金额: $ 26.49万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW029987%2F1
• 关键词: Defining; understanding; treating; lack; motivation

Schizophrenia is a barely understood brain disorder. Over the last fifty years, psychiatry has defined schizophrenia as a psychotic disorder, meaning suffering from delusions and hallucinations. Medication (antipsychotics) has been developed with some success. Paradoxically, most people with schizophrenia remain unable to work or have a family life even after psychosis is successfully treated. The reason is the poorly understood negative symptoms (along with cognitive symptoms). Negative symptoms refer to a lessening or absence of a previous function, namely motivation and emotional life. There is no licenced medication for its treatment. In this proposal I will focus on defining, understanding and treating poor motivation in schizophrenia. My impression is that the current scales for measuring motivation in schizophrenia are not fit for purpose. As 'negative symptoms', it is not a patient-friendly term, it is often avoided by clinicians, and other fields like neurology use different terms such as apathy (preventing joining forces in studies the same phenomenon as we have different words). Additionally, the approach to describe and treat poor motivation have not considered significant limitations. Poor motivation is the 'end point' behaviour but could be either a primary feature or secondary to other factors. These include medication-induced sedation, psychosis itself (avoidance), or a comorbid depressive state requiring completely different pharmacological non-pharmacological intervention.Working with world leaders in the field and under the partnership with Pr. Peter Jones, I have three primary aims in this proposal. First, to explore which of the novel measures of poor motivation can be used in clinical practice. We gather data in an international study to then work with experts by experience to define the best strategy to describe these symptoms in clinical practice in the future. Second, to describe the different steps of motivation (e.g. coming up with ideas, evaluation of effort needed or self-esteem level) using computer tasks. Then, to evaluate which secondary factor impacts each step of motivation. For instance, we anticipate that someone suffering from depression will consider too much effort to initiate any activity. In contrast, someone distracted with psychosis will not develop ideas or struggle to put a plan to establish them in place. Deconstructing the different steps and their secondary causes will inform clinicians to implement personalised interventions. Finally, we will explore how medication impacts motivation using novel statistical techniques. For instance, we have already found that a drug (clozapine) improves motivation by improving secondary factors: reducing psychosis severity and sedation (when clozapine is reduced). We can now analyse the impact of over 20 different medications on motivation using our cohort of patients carefully characterised. The end goal is to have detailed information to design a future clinical trial and help clinicians decide which medication is more effective for each aspect. This ambitious proposal builds upon two decades of experience treating people with schizophrenia and on three ethically approved research projects to be completed by 2022, 2023 and 2024, respectively. Funds are requested to ringfence time to analyse results and apply to a clinical trial formulated on the results. The study group is patients with chronic schizophrenia (>5 years since illness onset). They are disproportionally affected by motivation and emotional dysfunction compared to those with the first episode of psychosis. They are the core group seen at the Cambridge Psychosis Centre, an NHS unit that I lead.

精神分裂症是一种鲜为人知的脑部疾病。在过去的五十年中，精神病学将精神分裂症定义为一种精神病，这意味着患有妄想和幻觉。已经开发了一些成功的药物（抗精神病药）。矛盾的是，即使在成功治疗精神病之后，大多数精神分裂症患者仍无法工作或过家庭生活。原因是对负面症状（以及认知症状）的理解不足。负面症状是指降低或没有以前的功能，即动机和情感生活。没有持牌药物治疗。在这一建议中，我将专注于定义，理解和治疗精神分裂症的动机不良。我的印象是，目前测量精神分裂症动机的量表不适合目的。作为“负面症状”，它不是一个对患者友好的术语，通常是由临床医生避免的，而神经病学等其他领域则使用不同的术语，例如冷漠（防止与我们不同词相同的现象中的联合作用）。此外，描述和治疗不良动机的方法并未考虑重大局限性。动机不佳是“终点”行为，但可能是其他因素的主要特征或次要的。其中包括药物引起的镇静，精神病本身（避免）或合并症的抑郁状态，需要完全不同的药理学非药理学干预。彼得·琼斯（Peter Jones），我在这一建议中有三个主要目标。首先，探索哪些新型动机的新方法可以用于临床实践中。我们在一项国际研究中收集数据，然后通过经验与专家合作，以定义将来在临床实践中描述这些症状的最佳策略。第二，使用计算机任务描述动机的不同步骤（例如，提出想法，所需的努力或自尊心评估）。然后，评估哪些次要因素会影响动机的每个步骤。例如，我们预计患有抑郁症的人会考虑太多的努力来发起任何活动。相比之下，分心精神病的人不会发展思想或努力制定制定计划的计划。解构不同的步骤及其次要原因将通知临床医生实施个性化干预措施。最后，我们将探索用新颖的统计技术来探讨药物如何影响动机。例如，我们已经发现，一种药物（氯氮平）通过改善次要因素来改善动机：减少精神病的严重程度和镇静（减少氯氮平时）。现在，我们可以使用精心表征的患者组来分析20多种不同药物对动机的影响。最终目标是拥有详细的信息来设计未来的临床试验，并帮助临床医生确定哪种药物对每个方面更有效。这项雄心勃勃的提议基于对治疗精神分裂症患者的经验，并分别在2022年，2023年和2024年分别完成的三个经过道德认可的研究项目。要求资金响应时间分析结果，并适用于对结果提出的临床试验。研究组是慢性精神分裂症患者（疾病发作以来> 5年）。与患有精神病的第一集相比，它们受到动机和情绪功能障碍的影响不成比例。他们是在我领导的NHS单元的剑桥精神病中心看到的核心组。