Childhood trauma, hippocampal function, and anhedonia among those at heightened risk for psychosis

精神病高危人群中的童年创伤、海马功能和快感缺失

基本信息

批准号：
10825287
负责人：
Kathleen O'Brien
金额：
$ 3.32万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2024
资助国家：
美国
起止时间：
2024-01-01 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10825287
关键词：
Active Learning Affect Age Anhedonia Animal Model Area Brain Chronic Chronic stress Clinical Corpus striatum structure Data Data Analyses Decision Making Detection Development Diagnosis Diagnostic Disease Dopamine Early Intervention Early-life trauma Educational workshop Episodic memory Fellowship Functional disorder Funding Future Globus Pallidus Glucocorticoids Hippocampus Hospitalization Human Hydrocortisone Image Impairment Individual Intervention Interview Learning Mediating Mental Depression Mentorship Modeling National Institute of Mental Health Nucleus Accumbens Onset of illness Outcome Participant Pathway interactions Patient Self-Report Philadelphia Play Population Predisposition Process Psychological reinforcement Psychopathology Psychoses Public Health Publishing Quality of life Questionnaires Recording of previous events Reporting Research Resistance Rest Rewards Risk Rodent Role Sampling Scanning Schizophrenia Scientist Severities Signal Transduction Site Specificity Stimulus Stress Structure Symptoms Synapses System Training Trauma Ventral Tegmental Area Work biological adaptation to stress comorbidity early life adversity experience functional MRI scan functional disability functional outcomes high risk high risk population hypothalamic-pituitary-adrenal axis insight mesolimbic system neuroimaging neuromechanism novel novelty processing pediatric trauma pleasure power analysis psychosis risk recruit response reward processing schizophrenia spectrum disorder social training opportunity

项目摘要

PROJECT SUMMARY/ABSTRACT Individuals with schizophrenia spectrum disorders experience a range of symptoms which cause high levels of functional impairment, thus representing a large personal and public health burden. Similarly, individuals at clinical high risk (CHR) for the development of psychosis experience general work and academic impairments, social impairment, and reductions in quality of life that are evident even prior to the onset of full-threshold psychosis. Therefore, studies evaluating CHR populations can help to uncover how symptoms of schizophrenia first arise and indicate more effective avenues for early intervention. Of particular importance is the examination of negative symptoms, such as anhedonia, as they tend to present prior to the onset of positive symptoms, are more resistant to treatment, and are more strongly predictive of functional outcomes. Further, although anhedonia commonly occurs in those with psychosis, it also is a hallmark feature of depression, a disorder with high comorbidity in CHR individuals. Mounting evidence suggests that childhood trauma not only increases risk of developing psychosis, but is associated with anhedonia, specifically, across diagnoses, including for individuals with depression, as well as non-psychiatric controls. Further, childhood trauma has deleterious effects on the mesolimbic system, particularly the hippocampus, a region which animal models have recently implicated in the development of reward deficits underlying anhedonia. Despite these converging lines of research, no one, to date, has examine the mediating role of mesolimbic functioning in the relationship between childhood trauma and anhedonia. Therefore, the proposed study will examine the association between childhood trauma and anhedonia via the indirect effect of hippocampal function during novelty processing, which has been shown to engage dopaminergic reward systems. The proposed study, in the context of my sponsor's NIMH-funded R01, will recruit non-help-seeking 16-30 year olds who represent the full spectrum of psychosis-risk to complete self- report questionnaire and clinical interviews, with a subset completing both resting-state and task-based functional magnetic resonance imaging (fMRI) scans. Findings from the proposed study have the capacity to provide additional insight into previously established reward-related alterations associated with anhedonia, thus providing a novel framework to understand the relationship between childhood trauma and anhedonia. Further, we will explore potential differences in the association between childhood trauma, mesolimbic engagement, and anhedonia across CHR and non-CHR individuals to assess specificity. To complete this study, a training plan has been developed that consists of formal coursework, workshops, experiential learning, and mentorship. This fellowship would allow me to obtain additional training opportunities that would not otherwise be available to me, in order to develop the expertise in the pathophysiology of reward dysfunction, neuroimaging, and data analysis necessary to become an independent clinical scientist.

项目概要/摘要患有精神分裂症谱系障碍的个体会经历一系列症状，导致高水平的功能障碍，从而造成巨大的个人和公共健康负担。同样，个人在发生精神病的临床高风险（CHR）经历一般工作和学业障碍，社交障碍和生活质量下降甚至在完全阈值开始之前就很明显精神病。因此，评估 CHR 人群的研究有助于揭示精神分裂症的症状如何首先出现并表明早期干预的更有效途径。尤其重要的是考试阴性症状，例如快感缺乏，因为它们往往在阳性症状出现之前出现，对治疗更有抵抗力，并且对功能结果的预测能力更强。此外，虽然快感缺失通常发生在精神病患者身上，它也是抑郁症的一个标志性特征，抑郁症是一种患有抑郁症的疾病 CHR 个体的高合并症。越来越多的证据表明，童年创伤不仅会增加风险发展为精神病，但与快感缺失有关，特别是在各种诊断中，包括患有抑郁症的人以及非精神病对照者。此外，童年创伤具有有害影响关于中脑边缘系统，特别是海马体，动物模型最近暗示该区域导致快感缺乏的奖赏赤字的发展。尽管这些研究方向趋同，但没有人迄今为止，已经研究了中脑边缘功能在童年创伤之间关系中的中介作用和快感缺失。因此，拟议的研究将探讨童年创伤与快感缺乏是由于新奇事物处理过程中海马功能的间接影响，这已被证明参与多巴胺能奖励系统。拟议的研究，在我的发起人 NIMH 资助的 R01 的背景下，将招募代表所有精神病风险的非寻求帮助的 16-30 岁青少年来完成自我治疗报告调查问卷和临床访谈，其中一部分完成静息状态和基于任务的功能磁共振成像（fMRI）扫描。拟议研究的结果有能力提供对先前建立的与快感缺乏相关的奖励相关改变的额外见解，从而提供了一个新的框架来理解童年创伤和快感缺失之间的关系。更远，我们将探讨童年创伤、中脑边缘参与和 CHR 和非 CHR 个体的快感缺失来评估特异性。为了完成这项研究，需要制定培训计划其开发内容包括正式课程、研讨会、体验式学习和指导。这研究金将使我获得额外的培训机会，否则我将无法获得这些机会，为了发展奖赏功能障碍的病理生理学、神经影像学和数据分析方面的专业知识成为一名独立的临床科学家所必需的。