Stress Regulation, Working Memory, and Cognitive Disorganization In Adolescence

青春期的压力调节、工作记忆和认知紊乱

• 批准号: 9249221
• 负责人: Aysenil Belger
• 金额: $ 13.04万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-20 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9249221
• 关键词: 16 year old; Adolescence; Adolescent; Affect; Affective; Age; Amygdaloid structure; Anterior; Anxiety; Aphasia; Arousal; Attention; Behavior; Behavioral; Biological; Brain; Categories; Clinical; Cognition; Cognitive; Cognitive deficits; Development; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Dimensions; Disease; Eating; Electroencephalography; Electrophysiology (science); Epidemiology; Etiology; Functional Magnetic Resonance Imaging; Functional disorder; Genetic study; Goals; Health; Hormones; Hydrocortisone; Image; Impairment; Individual; Insula of Reil; Measurement; Measures; Medial; Mediating; Memory impairment; Modeling; Molecular Genetics; Neurobiology; Patient Self-Report; Performance; Phenotype; Physiological; Play; Prefrontal Cortex; Psychopathology; Psychotic Disorders; Recovery; Regulation; Reporting; Research Domain Criteria; Rest; Risk; Role; Salivary; Severities; Sex Characteristics; Short-Term Memory; Staging; Stress; Stress Tests; Symptoms; System; Time; Transcend; behavior measurement; behavioral construct; biological adaptation to stress; cingulate cortex; clinical risk; cognitive system; critical period; experience; functional outcomes; heart rate variability; negative affect; neurobiological mechanism; neuroimaging; neuropsychological; psychosocial; relating to nervous system; sex; sexual dimorphism

 DESCRIPTION (provided by applicant): Adolescence is a peak time for the emergence of the core symptoms of psychopathology. Cognitive disorganization (CD) is a key symptom dimension of psychosis that emerges most commonly in adolescence, reflects a disorganization of thought and is defined by the presence of bizarre behavior, alogia, and impaired attention. CD transcends DSM diagnostic categories, predicts the onset and severity of psychotic disorders, and is associated with neuropsychological impairment. Genetic studies have reported that CD is highly heritable, and therefore has been proposed as a promising phenotype for molecular genetic studies. Despite its critical role in heralding risk for psychosis, little is knon about the neurobiological underpinnings of CD in adolescents. It has been reported however that adolescents experiencing disorganization have significant deficits in working memory capacity (WMC) and arousal/stress regulation (ASR). These two behavioral constructs show dramatic maturational changes during adolescence, which are necessary for the transition to higher-level cognition, affect regulation and psychosocial adaptation. Despite the strong epidemiologic evidence for the role of stress in the etiology of psychosis, and the centrality of working memory impairments in psychosis, little is known about their contribution to CD in adolescence. Examining the neural and physiological systems associated with working memory and stress regulation in adolescence, and their contribution to CD severity, offers a critical step in elucidating the pathophysiological mechanisms that contribute to the onset of psychosis. This approach is consistent with the RDoC framework, which encourages using converging measurements to study the underlying neurobiology of domains (Cognitive System and Arousal Regulation in this proposal), and constructs (working memory capacity and stress regulation) that represent fundamental behaviors expressed by individuals with clinical risk symptoms for psychosis. We will use a multimodal approach integrating functional neuroimaging, electrophysiological, and behavioral measures to ascertain converging measures of working memory and arousal/stress regulation constructs across neural, physiological, and behavioral units, and to characterize the contributions of atypical ASR and impaired WMC in the severity of CD symptoms measured through clinical scales. In Aim 1, we will evaluate the contributions of working memory impairments and atypical arousal/stress regulation in 180 adolescents (ages 9-16) to the severity of CD symptom. In AIM 2 we will model the relationship between WM and ASR constructs and their impact on CD severity. In AIM 3, we will examine the longitudinal trajectory of CD symptom severity, behavioral and electrophysiological measures of WM and ASR, and their associations with baseline neural, behavioral, and physiological measures acquired in AIMs 1 and 2. For each aim, we will explore the modulatory role of sex differences and pubertal maturation on stress-regulation and working memory during adolescence, and their influence in determining functional outcomes. IMPACT: Understanding the neural and physiological systems associated with working memory capacity and stress regulation in adolescence, and their contribution to CD severity, is a crucial step for elucidating the core pathophysiological mechanisms that promote the emergence and exacerbation of psychosis.

 描述（应用程序提供）：青少年是出现精神病学核心症状的高峰时间。认知混乱（CD）是精神病的关键症状维度，在青少年中最常见，反映了思想的混乱，并由奇异行为，艾洛吉亚和注意力受损而定义。 CD超越了DSM诊断类别，预测精神病的发作和严重程度，并与神经心理学障碍有关。遗传研究报告说，CD是高度遗传的，因此已被提出是分子遗传研究的有望表型。尽管在预示精神病风险中的作用至关重要，但对青少年CD的神经生物学基础的knon并不几乎没有。然而，据报道，青少年经历混乱的工作记忆能力（WMC）和唤醒/压力调节（ASR）存在明显的缺陷。这两种行为构建体在青少年期间显示出巨大的成熟变化，这对于过渡到高级认知所必需，影响调节和社会心理适应。尽管有强烈的流行病学证据表明，压力在精神病的病因学中的作用以及精神病中工作记忆障碍的中心性，但对青少年青春期CD的贡献知之甚少。检查与青少年的工作记忆和压力调节有关的神经和物理系统及其对CD严重性的贡献，提供了关键的步骤 在阐明导致精神病发作的病理生理机制方面。这种方法与RDOC框架一致，RDOC框架鼓励使用融合测量结果研究域的潜在神经生物学（该提案中的认知系统和唤醒调节），并构建（工作记忆力和压力调节）代表具有临床风险符号的个人表达的基本行为。我们将使用一种多模式的方法来整合功能性神经影像学，电生理和行为测量，以确定跨神经，物理和行为单位的工作记忆和唤醒/压力调节结构的收敛测量，以表征非应用ASR和Inypical ASR和受损WMC在CD符号中的贡献的贡献。在AIM 1中，我们将评估180名青少年（9-16岁）对CD症状的严重程度的工作记忆障碍和非典型唤醒/压力调节的贡献。在AIM 2中，我们将模拟WM和ASR构建体之间的关系及其对CD严重性的影响。在目标3中，我们将检查WM和ASR的CD症状降温，行为和电生理学测量的纵向轨迹，以及它们与目标1和2中获得的基线神经，行为和身体措施的关联。对于每个目标，我们将探索对性别差异和封度的调节作用，在确定工作过程中，我们将探索对性别差异的作用，以及在工作过程中的影响。影响：了解与青少年的工作记忆能力和压力调节有关的神经和物理系统及其对CD严重程度的贡献，是阐明核心病理生理机制的关键步骤，促进促进精神病的出现和加剧。