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）生物标志物的发现和验证以及特定的挑战主题，03- mh -101：精神障碍中的生物标志物。该应用程序采用以构建为导向的方法来识别流行形式的精神疾病的生物标志物。具体来说，本研究的重点是两个关键性格构念的生理反应指标，这两个构念在神经生物学和行为中都有直接的参照：(1)恐惧/无所畏惧，(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。抑制控制的变化被认为反映了在远端目标服务中调节情感和行为反应的大脑系统功能的个体差异。目前的建议建立在广泛的初步研究的基础上，旨在开发敏感而精确的心理测量方法来测量性格恐惧和去抑制（外化）倾向，并确定这些结构的大脑相关性。我们认为，由于这些结构为神经生物学系统与可测量的行为偏差之间的联系提供了具体的基础，因此可以作为与精神病理学相关的基于生理学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，包括收集来自大量在押罪犯样本的心理测量、诊断和生理（包括脑电图/ERP）数据。将进行分析，以确定性格恐惧和去抑制的构念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病）和不同的生理指标相关联。此外，先进的皮层电分析技术，包括脑电图时频分解、神经源成像和相位相干分析，将应用于大脑反应数据，以阐明导致恐惧/无畏和去抑制个体差异的神经回路，并阐明这些回路功能的偏差如何导致不同的精神障碍。这项工作有望通过研究这些障碍与明确的神经生物学参考物的统一结构的关系，促进我们对不同精神障碍的重叠和独特方面的理解。这类工作可以为直接评估与精神病理学相关的个体差异结构提供基础，也可以改善对精神疾病发展的生物风险个体的识别。

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.