Pubertal hormone levels differentially modulate the neural circuits implicated in emotion dysregulation in youth with psychopathology

项目概要/摘要：研究项目（4） 青春期激素水平差异调节神经回路牵连 在青年精神病患者情绪失调中的作用 据估计，超过20%的美国青少年患有严重的精神病理学，包括压力， 情绪焦虑和行为障碍患有这些疾病的患者表现出情绪失调， NIMH的研究领域标准框架内的认知控制结构的一部分。关键的大脑 情绪调节的基础回路包括杏仁核、额叶和顶叶皮质， 儿童情绪反应增强，通常与额叶和顶叶活动失常有关。 众所周知，睾酮（T）和皮质醇（C）会间接影响成年人这些区域的神经处理， 它们在异常情绪反应中的具体作用尚不清楚，尚未对儿童进行研究。 因此，我们在这项研究中的目标是确定T和C反应性在调节神经反应相关的作用， 在有和没有精神病理学的青少年中的情绪调节（即，情绪调节问题）。 与NIH减轻精神障碍负担的使命一致，这项拟议的工作将产生更好的结果。 了解情绪调节的生物学机制，从而支持发展 新的和改进的干预措施，为青少年与精神病理学。具体来说，当前提案的目标是 目的：（i）确定T反应性调节青少年情绪调节和神经功能的程度， 情绪调节问题相对于典型发展（TD）青年，以及青春期状态 在每组中介导这种关系;（ii）确定C反应在情绪调节和神经功能中的作用。 功能在青年情绪失调和TD青年，以及在何种程度上青春期状态介导 这些关系;（iii）确定生物性别在调节T和C反应性的作用， 与TD青年相比，情绪调节障碍青年的情绪调节。我们认为鉴定性别 在这种情况下的差异是至关重要的，因为已知的激素功能和 这些疾病在青春期的发病率。 这些目标将通过招募210名参与者（9-15岁;一半男性;一半社区）来实现 对照组），包括105例精神病理学（即，情绪调节问题）从门诊心理健康 诊所。参与者将完成一项功能磁共振成像协议，评估社交挑战后的情绪调节 设计了一个T反应的范例。我们的试验数据表明，增加T反应性改善情绪 调节，但损害它在青年与精神病理学。此外，C反应性似乎也 改善健康青年情绪调节，但尚未在精神病理学青年中进行检查。是 预计拟议的研究将显示T和C反应性各自影响行为的程度， 在患有精神病理学的青少年中，尤其是在青春期， 过渡，以及生物性别的作用。由于目前的精神病理学干预策略不考虑 激素机制，这些数据将是至关重要的新的治疗方法的发展。

Project Summary/Abstract: Research Project (4) Pubertal hormone levels differentially modulate the neural circuits implicated in emotion dysregulation in youth with psychopathology Estimates indicate that over 20% of American adolescents suffer from serious psychopathology, including stress, mood, anxiety, and behavioral disorders. Patients with these disorders show emotional dysregulation, which is part of the cognitive control construct within the NIMH’s Research Domain Criteria framework. The critical brain circuitry underlying emotional regulation is known to include the amygdala, frontal, and parietal cortices, with heightened emotional responses in children most commonly linked to aberrations in frontal and parietal activity. Testosterone (T) and cortisol (C) are known to indirectly affect neural processing in these regions in adults, but their particular role in aberrant emotional responses is unknown and studies in children have yet to be conducted. Thus, our goal in this study is to identify the role of T and C reactivity in modulating neural responses associated with emotion regulation in adolescents with and without psychopathology (i.e., emotion regulation issues). Consistent with the NIH’s mission to reduce the burden of mental disorders, the proposed work will yield a better understanding of the biological mechanisms underlying emotion regulation, and thereby support the development of new and improved interventions for adolescents with psychopathology. Specifically, the current proposal aims to: (i) determine the extent to which T reactivity modulates emotion regulation and neural function in youth with emotion regulation issues relative to typically-developing (TD) youth, and the degree to which pubertal status mediates this relationship in each group; (ii) determine the role of C reactivity in emotion regulation and neural function in youth with emotional dysregulation and TD youth, and the degree to which pubertal status mediates these relationships; and (iii) identify the role of biological sex in modulating T and C reactivity in the context of emotion regulation in youth with emotional dysregulation relative to TD youth. We believe identifying sex differences in this context is critical, as there are known sex differences in both hormonal functioning and the prevalence of these disorders during adolescence. These aims will be accomplished by recruiting 210 participants (aged 9-15 years; half male; half community controls), including 105 with psychopathology (i.e., emotion regulation issues) from outpatient mental health clinics. Participants will complete an fMRI protocol assessing emotion regulation following a social challenge paradigm designed to elicit a T response. Our pilot data indicates that increased T reactivity improves emotion regulation in healthy youth, but impairs it in youth with psychopathology. Further, C reactivity also appears to improve emotion regulation in healthy youth, but has not been examined in youth with psychopathology. It is anticipated that the proposed study will show the extent to which T and C reactivity each impact behavior and the neural activity underlying emotion regulation in youth with psychopathology, particularly during the pubertal transition, and the role of biological sex. As current intervention strategies for psychopathology do not consider hormonal mechanisms, these data will be critical in the development of novel treatment approaches.