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

项目摘要/摘要：研究项目(4) 青春期激素水平不同地调节所涉及的神经回路 青少年情绪调节障碍与精神病的关系 据估计，超过20%的美国青少年患有严重的精神病态，包括压力， 情绪、焦虑和行为障碍。患有这些障碍的患者表现出情绪失调，这是 NIMH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 众所周知，情绪调节的基本回路包括杏仁核、额叶和顶叶皮质， 儿童情绪反应增强最常与额叶和顶叶活动的异常有关。 已知睾酮(T)和皮质醇(C)间接影响成年人这些区域的神经处理，但 它们在异常情绪反应中的特殊作用尚不清楚，对儿童的研究尚未进行。 因此，我们在这项研究中的目标是确定T和C反应性在调节相关神经反应中的作用 在有和没有精神疾病(即情绪调节问题)的青少年中进行情绪调节。 与NIH减轻精神障碍负担的使命一致，拟议的工作将产生更好的 理解情绪调节背后的生物学机制，从而支持发展 为患有精神病的青少年提供新的和改进的干预措施。具体地说，目前的提案旨在 以：(I)确定T反应性对青年情绪调节和神经功能的调节程度 与典型发育(TD)青年有关的情绪调节问题，以及青春期状态的程度 在每组中调节这种关系；(Ii)确定C反应性在情绪调节和神经中的作用 情绪调节障碍青少年和TD青少年的功能及青春期状态在多大程度上的调节 这些关系；以及(Iii)确定生物性别在调节T和C反应性方面的作用 情绪调节障碍青少年相对于TD青少年的情绪调节。我们相信辨别性别 在这方面的差异是至关重要的，因为已知的性别差异在激素功能和 这些疾病在青春期的流行情况。 这些目标将通过招募210名参与者(9-15岁，一半是男性，一半是社区)来实现 对照)，其中105人患有精神病理(即情绪调节问题)，来自门诊精神健康 诊所。参与者将在社交挑战后完成一项评估情绪调节的功能磁共振成像方案 旨在引起T反应的范例。我们的试点数据表明，T细胞反应性增加会改善情绪 在健康的青年中调节，但在患有精神病的青年中损害它。此外，C的反应性似乎也 在健康青年中改善情绪调节，但在青年精神病患者中未见研究。它是 预计拟议的研究将显示T和C反应性各自影响行为和 青少年情绪调节的神经活动与精神病理，特别是青春期 过渡，以及生物性行为的作用。因为目前的精神病理学干预策略没有考虑到 荷尔蒙机制，这些数据将是开发新的治疗方法的关键。

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.