Reward processing in genetic frontotemporal dementia and mood disorders

遗传性额颞叶痴呆和情绪障碍的奖励处理

基本信息

批准号：
10338052
负责人：
DAVID C PERRY
金额：
$ 80.74万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10338052
关键词：
Affect Affective Age of Onset Alcohols Amygdaloid structure Anatomy Animal Model Anterior Arousal Atrophic Autonomic nervous system Behavior Behavioral Behavioral Symptoms Bipolar Disorder C9ORF72 Caregivers Characteristics Classification Climacteric Clinical Trials Dementia Diagnosis Disease Disease Marker Early Diagnosis Elderly Elements Emotional Emotions Evaluation Family Family member Fatigue Food Frontotemporal Dementia Frontotemporal Lobar Degenerations Functional Imaging Functional disorder Galvanic Skin Response Genes Genetic Goals Health Services Accessibility Heart Rate Hypersensitivity Impaired cognition Individual Inherited Insula of Reil Laboratories Lead Link Major Depressive Disorder Measures Mental disorders Methods Mood Disorders Moods Motivation Mutation National Institute of Mental Health Negative Valence Nerve Degeneration Neuroanatomy Nucleus Accumbens Onset of illness Patient Care Patients Personality Phenotype Prognosis Psychiatric Diagnosis Psychophysiology Punishment Reporting Research Research Domain Criteria Rewards Series Services Severities Site Social Functioning Specialist Stimulus Symptoms Task Performances Testing Work autosomal dominant mutation base behavior change behavioral variant frontotemporal dementia cingulate cortex classification algorithm clinical care diagnostic accuracy diagnostic criteria disease-causing mutation emotional functioning emotional symptom functional disability improved member mood symptom neuropsychiatry patient response psychiatric symptom reward processing sex social social contact targeted treatment therapeutic target white matter

项目摘要

ABSTRACT Frontotemporal dementia (FTD) is a common neurodegenerative cause of an early age-of-onset dementia. Changes in personality, social, and emotional function characterize the behavioral variant of FTD (bvFTD) and since there is partial overlap with the symptoms of psychiatric illness patients often receive early diagnoses of major depressive disorder (MDD) or bipolar illness (BPAD). A delay in receiving the correct diagnosis negatively impacts the care these patients receive. 10-40% of FTD is inherited, most commonly by autosomal dominant mutations in one of three genes (MAPT, GRN, and C9orf72). By studying the earliest behavior changes in individuals who carry one of these FTD mutations we can identify features that distinguish mood disorders from FTD. Reward processing involves a determination of what an individual finds pleasant and will pursue or work for. Many of the symptoms in bvFTD reflect a shift in reward processing, including changes in motivation for food, sex, alcohol, money, and social approval. Patients with bvFTD have been shown to be particularly insensitive to things that others would find negative or aversive. The proposed research will compare reward processing in presymptomatic patients with genetic FTD and those with mood disorders. We will study 60 patients with presymptomatic genetic FTD, 60 gene negative members of the same families, 40 patients with bvFTD, 40 with MDD, 40 with BPAD, and will compare them with 60 healthy controls. The central hypothesis of this proposal is that reward processing differs in characteristic ways between bvFTD, even in its early stages, and mood disorders in a way that reflects the vulnerable anatomy of these disorders. In Aim 1 we will identify differences in reward processing abnormalities that distinguish bvFTD from mood disorders using a series of laboratory-based paradigms during which we will record patient responses and measure their autonomic nervous system reactivity to rewarding stimuli. In Aim 2 we will assess the diagnostic accuracy of the reward measures and classification approach from Aim 1 in separating early bvFTD from mood disorders. In Aim 3 we will correlate patients' reward task performance with the severity of their mood and behavioral symptoms and will identify the neuroanatomic correlates through structural and functional imaging. The results of the proposed research will improve early diagnosis of bvFTD through objective, laboratory based measures, resulting in better clinical care and facilitation of clinical trials; suggest reward-based targets for symptomatic therapies and reward-based measures of behavior to apply in FTD animal models. It will also expand the understanding of reward behaviors and their anatomic correlates in psychiatric illness, allowing for more targeted therapies.

抽象的额颞痴呆（FTD）是年龄较小的痴呆症的常见原因。人格，社交和情感功能的变化是FTD（BVFTD）和由于与精神病患者的症状有部分重叠重度抑郁症（MDD）或躁郁症（BPAD）。延迟接受正确的诊断负面影响这些患者接受的护理。 FTD的10-40％是继承的，最常见的是常染色体三个基因之一（MAPT，GRN和C9ORF72）中的主要突变。通过研究最早的行为携带这些FTD突变之一的个体的变化，我们可以识别出区分情绪的功能 FTD的疾病。奖励处理涉及确定个人发现令人愉快的东西追求或工作。 BVFTD中的许多症状反映了奖励处理的转变，包括变化食物，性别，酒精，金钱和社会认可的动机。 BVFTD患者已显示为对别人会发现负面或厌恶的事物特别不敏感。拟议的研究将比较遗传FTD的预症状患者和情绪障碍患者的奖励处理。我们将研究60名患有遗传性FTD的患者，同一家族的60个基因阴性成员，40例 BVFTD的患者，40例MDD，40例BPAD，将与60个健康对照进行比较。中央该提议的假设是，奖励处理以BVFTD的特征方式不同，即使早期阶段和情绪障碍以反映这些疾病的脆弱解剖结构的方式。在目标1中我们将确定奖励处理异常的差异，这些异常将BVFTD与情绪障碍区分开一系列基于实验室的范例，我们将记录患者的反应并衡量他们的反应自主神经系统对奖励刺激的反应性。在AIM 2中，我们将评估 AIM 1的奖励措施和分类方法将早期BVFTD与情绪障碍分开。在AIM 3中，我们将将患者的奖励任务表现与他们的情绪和行为的严重性相关联症状并将通过结构和功能成像识别神经解剖学相关。结果在拟议的研究中，将通过基于实验室的措施来改善BVFTD的早期诊断，导致更好的临床护理和临床试验的促进；建议有症状的基于奖励的目标在FTD动物模型中适用的疗法和基于奖励的行为措施。它也将扩大了解奖励行为及其解剖学在精神病中的相关性，允许更多靶向疗法。