Trait Fear and Disinhibition in Impulse Control Disorders

描述(由申请人提供)：本申请涉及广泛的挑战领域(03)生物标记物的发现和验证以及特定的挑战主题，03-MH-101：精神疾病中的生物标记物。该应用程序采用面向结构的方法来识别流行形式的精神疾病的生物标记物。具体地说，建议的工作集中在两个关键的倾向性结构的生理反应指标上，这两个结构在神经生物学和行为中都有直接的参照：(1)恐惧/无畏，和(2)抑制控制。恐惧和无畏的差异被认为反映了大脑防御动机系统敏感度的个体差异。抑制性控制的差异被认为反映了大脑系统功能的个体差异，这些系统调节为远端目标服务的情感和行为反应。目前的建议建立在广泛的初步研究的基础上，旨在开发敏感和精确的倾向性恐惧和去抑制性(外化)倾向的心理测量方法，并确定这些结构的大脑关联。我们认为，这些结构，因为它们提供了将神经生物系统与可测量的行为偏差联系起来的具体基础，可以作为与精神病理学相关的基于生理的个体差异科学的重要参考。一项为期两年的工作计划被提出，涉及从被监禁罪犯的大样本中收集心理测量、诊断和生理(包括脑电/事件相关电位)数据。将进行分析，以确定心理测量学操作的倾向性恐惧和去抑制的结构如何与不同形式的精神病理学(包括冲动控制障碍、附属人格障碍和临床访谈评估的精神变态)和不同的生理指标有关。此外，先进的大脑皮质分析技术，包括脑电时频分解、神经源成像和相位相干分析，将被应用于大脑反应数据，以阐明在恐惧/无畏和去抑制的个体差异背后的神经回路，并阐明这些回路的功能偏差如何导致不同的精神障碍。这项工作承诺通过研究与具有明确神经生物学参照的统一结构有关的不同精神障碍的重叠和独特方面来促进我们对这些方面的理解。这类工作可以为与精神病理学相关的个体差异结构的直接神经生理学评估以及改进对精神疾病发展的生物风险个体的识别提供基础。 公共卫生相关性：对冲动控制(‘外化’)障碍的生物学基础进行研究，对于了解这类疾病的原因并制定有效的预防和治疗方法至关重要。这项拟议的工作试图通过研究两个在神经生物学和行为中有直接参照的关键倾向结构来连接临床诊断实体和潜在的生物系统：(1)恐惧/无畏，和(2)抑制控制。目前的工作将有助于理解导致与精神病理学相关的个体差异的大脑回路，并提供信息，有助于以更易于进行生物分析的方式重塑障碍定义。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (03) Biomarker Discovery and Validation and specific Challenge Topic, 03-MH-101: Biomarkers in Mental Disorders. The application takes a construct-oriented approach to the identification of biomarkers for prevalent forms of mental illness. Specifically, the proposed work focuses on physiological response indicators of two key dispositional constructs that have direct referents in neurobiology as well as behavior: (1) fear/fearlessness, and (2) inhibitory control. Variations in fear and fearlessness are posited to reflect individual differences in the sensitivity of the brain's defensive motivational system. Variations in inhibitory control are posited to reflect individual differences in the functioning of brain systems that modulate affective and behavioral response in the service of distal goals. The current proposal builds on extensive preliminary research directed at developing sensitive and precise psychometric measures of dispositional fear and disinhibitory (externalizing) tendencies and identifying brain correlates of these constructs. We propose that these constructs, because they provide a concrete basis for linking neurobiological systems to measurable deviations in behavior, can serve as important referents for a physiologically based science of individual differences relevant to psychopathology. A two-year program of work is proposed involving collection of psychometric, diagnostic, and physiological (including EEG/ERP) data from a large sample of incarcerated offenders. Analyses will be performed to establish how constructs of dispositional fear and disinhibition, operationalized psychometrically, relate to varying forms of psychopathology (including impulse control disorders, affiliated personality disorders, and psychopathy as assessed by clinical interview) and to varying physiological indicators. In addition, advanced electrocortical analysis techniques including EEG time-frequency decomposition, neural source imaging, and phase coherence analysis will be applied to the brain response data to elucidate neural circuits that underlie individual variations in fear/fearlessness and disinhibition and to clarify how deviations in the functioning of these circuits contribute to varying mental disorders. This work promises to advance our understanding of overlapping and distinctive aspects of varying mental disorders by studying these disorders in relation to unifying constructs with clear neurobiological referents. Work of this kind can provide the basis for direct neurophysiological assessment of individual difference constructs relevant to psychopathology as well as improved identification of individuals at biological risk for the development of mental illness. PUBLIC HEALTH RELEVANCE: Research on the biological bases of impulse control ('externalizing') disorders is essential to an understanding of the causes of such disorders and to developing effective methods for preventing and treating them. The proposed work seeks to bridge clinical-diagnostic entities with underlying biological systems by studying two key dispositional constructs that have direct referents in neurobiology as well as behavior: (1) fear/fearlessness, and (2) inhibitory control. The current work will contribute to an understanding of brain circuits that give rise to individual differences relevant to psychopathology, and provide information that can help to reshape disorder definitions in ways that make them more amenable to biological analysis.