Neurobiological Underpinnings of Pain-Related Symptoms in Early Onset Psychosis

摘要 早发性精神病患者的远期预后较差，残留率较高。 与成人起病精神病病例相关的症状和残疾。患有EOP的儿童通常报告为中度到 剧烈疼痛，不能用可发现的原因解释，也不能与客观发现相关联(例如， 发炎、肿胀或发红)。EOP患者报告的疼痛导致严重的功能障碍 对儿童有害，并妨碍自理等基本活动。而异常的疼痛感知和处理在 成年精神病患者的临床、行为和神经生物学特征已有文献记载 在EOP中与疼痛相关的研究很少。EOP患者的疼痛特征将提供一种 这种现象的早期阶段、病程以及一段时期的发展窗口 活跃的中枢神经系统成熟。这项提议的目标有两个。目标1是评估男性和女性 EOP患者(N=30，13-18岁)，使用临床仪器告知疼痛严重程度和质量， 躯体化、中枢敏感化和心理健康。将发放一套平行的临床调查问卷。 在年龄-性别匹配的健康对照组(HCS，N=30)和两个匹配的临床对照条件中；复杂 局部疼痛综合征(CRPS，N=30)和注意缺陷/多动障碍(ADHD，N=30)。目标2 是确定EOP患者失调的疼痛感知和处理的行为和神经相关性 (n=30)和(n=30)。对于目标2，我们建议通过将结构化的 DSM-5(SCID-V)Axis I诊断的临床访谈，以及Kiddie时间表中的其他模块 情感障碍和精神分裂症(KSAD)、简明精神病评定量表(BPRS)和积极与消极 症状量表(PANSS)，以及疼痛敏感性评估(定量感觉测试)、认知和 中枢神经系统的功能和结构使用基于磁共振成像(MRI)的方法。我们还将探索 功能近红外光谱(FNIRS)在EOP中的应用FNIRS是一种非侵入性、经济高效的移动 尚未被广泛应用于EOP的神经成像方法。我们的主要假设是EOP患者 出现严重的精神症状会表现出强烈的疼痛表型，而 中枢神经系统(CNS)结构参与痛觉和感觉运动过程的自上而下调节 都是反常的。为了验证我们的假设，我们提出了以下具体目标。目标1：描述 EOP儿童的疼痛表现。目标2：确定失调性疼痛的行为和神经相关性 EOP中的感知和加工。探索性目标3：定义EOP中静息状态的中枢神经系统功能特性 使用fNIR。研究EOP患者的失调疼痛感知和处理，我们的波士顿儿童 医院团队将利用我们在儿科疼痛和精神病学、疼痛方面的临床和研究专业知识 神经生物学、神经成像、生物统计学等领域。

ABSTRACT Patients with early onset psychosis (EOP) demonstrate poorer long-term prognosis and higher rates of residual symptoms and disability relative to cases of adult-onset psychosis. Children with EOP often report moderate to severe pain, which is not explained by discoverable causes or associated with objective findings (e.g., inflammation, swelling, or redness). Pain reported by EOP patients introduces significant functional impairment for the child and hinders basic activities such as self-care. While abnormal pain perception and processing in adults with psychosis has been documented, the clinical, behavioral, and neurobiological characteristics associated with pain in EOP have rarely been studied. A characterization of pain in EOP patients will provide a developmental window into earlier stages of this phenomenon and course of the illness as well as during a period of active CNS maturation. The objective of this proposal is two-fold. Objective 1 is to evaluate male and female EOP patients (N=30, 13-18 years of age) with clinical instruments informing on pain severity and quality, somatization, central sensitization and mental health. A parallel set of clinical questionnaires will be administered in age-gender matched healthy controls (HCs, N=30) and two matched clinical comparator conditions; complex regional pain syndrome (CRPS, N=30) and attention-deficit/hyperactivity disorder (ADHD, N=30). Objective 2 is to identify behavioral and neural correlates of dysregulated pain perception and processing in EOP patients (N=30) and HCs (N=30). For Objective 2, we propose to phenotype participants by combining the Structured Clinical Interview for DSM-5 (SCID-V) Axis I diagnoses, with additional modules from the Kiddie Schedule for Affective Disorders and Schizophrenia (KSAD), Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS), alongside assessment of pain sensitivity (quantitative sensory testing), cognition, and CNS function and structure using magnetic resonance imaging (MRI) based methods. We will also explore the utility of functional near infrared spectroscopy (fNIRS) in EOP. fNIRS is a non-invasive, cost-effective, and mobile neuroimaging method that has not been widely used in EOP. Our overarching hypothesis is that EOP patients presenting with severe psychiatric symptoms will present with a robust pain phenotype, while the function of central nervous system (CNS) structures implicated in top-down regulation of pain and sensorimotor processing are aberrant. To test our hypothesis, we propose the following Specific Aims. Aim 1: Characterize the presentation of pain in children with EOP. Aim 2: Define behavioral and neural correlates of dysregulated pain perception and processing in EOP. Exploratory Aim 3: Define resting-state CNS functional properties in EOP using fNIRS. To study dysregulated pain perception and processing in patients with EOP, our Boston Children’s Hospital based team will leverage our clinical and research expertise in pediatric pain and psychiatry, pain neurobiology, neuroimaging, biostatistics, among other domains.