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志物。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志物。具体来说，拟议的工作集中在两个关键的性格结构，在神经生物学以及行为的直接引用生理反应指标：（1）恐惧/无畏，（2）抑制控制。恐惧和无畏的变化被认为反映了大脑防御动机系统敏感性的个体差异。抑制控制的变化被认为反映了大脑系统功能的个体差异，这些大脑系统调节情感和行为反应，为远端目标服务。目前的建议建立在广泛的初步研究，旨在发展敏感和精确的心理测量的气质恐惧和去抑制（外化）的倾向，并确定这些结构的大脑相关。我们建议，这些结构，因为它们提供了一个具体的基础，将神经生物学系统的行为可测量的偏差，可以作为重要的参考生理学为基础的科学的个体差异相关的精神病理学。提出了一个为期两年的工作计划，涉及收集心理测量，诊断和生理（包括EEG/ERP）数据从一个大样本的被监禁的罪犯。将进行分析，以确定如何结构的性格恐惧和去抑制，操作心理测量学，涉及到不同形式的精神病理学（包括冲动控制障碍，附属人格障碍，精神病的临床访谈评估）和不同的生理指标。此外，先进的皮层电分析技术，包括EEG时间频率分解，神经源成像和相位相干性分析将应用于大脑反应数据，以阐明神经回路，这些回路是恐惧/无畏和去抑制的个体差异的基础，并阐明这些回路的功能偏差如何导致不同的精神障碍。这项工作有望通过研究这些疾病的统一结构与明确的神经生物学参照物，促进我们对不同精神疾病的重叠和独特方面的理解。这种工作可以提供直接的神经生理学评估的个体差异结构相关的精神病理学，以及改善识别个人的生物风险的精神疾病的发展。 公共卫生相关性：研究冲动控制（“外化”）障碍的生物学基础对于了解此类障碍的原因以及开发预防和治疗它们的有效方法至关重要。拟议的工作旨在通过研究两个在神经生物学和行为中具有直接参照物的关键倾向性结构，将临床诊断实体与潜在的生物系统联系起来：（1）恐惧/无畏，（2）抑制控制。目前的工作将有助于理解引起与精神病理学相关的个体差异的大脑回路，并提供有助于重塑疾病定义的信息，使其更适合生物学分析。

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.