Biobehavioral Mechanisms for Severe Disruptive Behavior in Adolescent Girls

描述（由申请人提供）：破坏性行为障碍（DBD）和症状在男性中更为普遍，但在女性中却呈上升趋势，其影响对女孩的身心健康和生活质量具有破坏性。女性DBD的发病和上升通常表现在青春期，这是一个以剧烈的激素变化和伴随的青春期成熟为特征的发育阶段。我们的工作模型强调，这种发展的共同发生不是巧合。这项研究的总体目标是检查压力和性激素是否作为DBD症状的生物行为途径。拟议的项目将检查DBD的组成部分，特别是专注于无情/无情的特质作为一个重要的性格弱点，可靠地预测DBD的严重性和持久性。此外，神经生物学证据暗示压力和性激素在CU特征的表达中，具有显着的活动和神经回路的调制，其例示了同情心和冷酷无情。关于女性青少年DBD的研究很少，更少的是探讨症状表达背后的生物行为机制。此外，许多关于DBD途径的文献主要是从男性研究中推断出来的;当对女性进行检查时，她们通常表现出轻度至中度严重程度的DBD症状和CU特征。本研究将对该领域产生重大影响，因为它针对的是研究不足的女性人群，这些女性具有一系列DBD症状和严重程度较高的CU特征。我们已经获得许可，在南橡树女子学校检查压力和性激素，这是一所为威斯康星州最严重的青少年女性罪犯提供治疗的惩教机构。在两天内无创收集唾液10次，以捕获皮质醇、睾酮、脱氢表雄酮（DHEA）和雌二醇的昼夜节律。这种收集策略平行于最近的一项调查，在被监禁的男性青少年，从而允许探索性调查的性别相似性和性别差异的生物行为机制的基础CU性状表达和DBD症状的表达，而不会产生额外的费用。这项研究的最终产品将是获得一组推定的生物标志物，这些生物标志物将是该领域武器库中了解DBD风险、表达和预防的有用工具。捕获相互作用的多种激素是创新的，有可能导致CU性状表达和DBD风险的“生物特征”。该项目将为DBD和CU特征的生物行为机制研究的未来计划提供基础，通过跨学科研究，帮助弥合实验室研究与应用于现实世界问题之间的差距。调查团队由新的/早期完成的调查人员和经验丰富的导师/顾问组成，他们具有数十年的跨学科研究经验。 公共卫生相关性：深入了解严重破坏性行为障碍（DBD）潜在风险的心理生物学机制对于预防和治疗DBD至关重要。本提案针对具有非常高范围的DBD症状和问题的女孩的新人群，构成了对其推定生物标志物的首批调查之一。这项研究将对该领域产生重大影响，因为它采用了多种压力和性激素，提高了揭示女性青少年DBD独特生物特征的可能性。冷酷/无情感特征的行为表现被特别地作为神经生物学信息用于实例化DBD风险。目前的建议与最近的一项调查，被监禁的男性青少年，允许探索性别的相似性和差异。

DESCRIPTION (provided by applicant): Disruptive behavior disorders (DBD) and symptoms are more prevalent in males, yet they are on the rise in females and their impact is devastating for girls' mental and physical health and quality of life. The onset and rise in DBD in females typically manifests in adolescence, a developmental stage characterized by dramatic hormonal changes and concomitant pubertal maturation. Our working model emphasizes that this developmental co-occurrence is not a coincidence. The overarching goal of the proposed research is to examine if stress and sex hormones operate as biobehavioral pathways to DBD symptoms. The proposed project will examine the components of DBD, specifically focusing on callous/unemotional traits as an important dispositional vulnerability which reliably predicts DBD severity and persistence. Moreover, neurobiological evidence implicates stress and sex hormones in the expression of CU traits, with notable activity and modulation of the neurocircuitry which instantiates empathy and callousness. There is little research on DBD in female adolescents, and even less which investigates biobehavioral mechanisms underlying symptom expression. Moreover, much of the literature that has been conducted about pathways to DBD largely extrapolates from research with males; when females are examined, they typically express DBD symptoms and CU traits in the mild-moderate range of severity. The present investigation will have a significant impact on the field because it targets an under-studied population of females with a range of DBD symptoms and CU traits with a high range of severity. We have received permission to examine stress and sex hormones in Southern Oaks Girls School, a correctional facility that offers treatment for the most severe adolescent female offenders in the state of Wisconsin. Saliva will be noninvasively collected ten times across two days to capture the diurnal rhythm of cortisol, testosterone, dehydroepiandrosterone (DHEA), and estradiol. This collection strategy parallels a recent investigation in incarcerated male adolescents, thereby permitting exploratory investigation of sex similarities and sex differences in the biobehavioral mechanisms underlying CU trait expression and DBD symptom expression without incurring additional cost. The end- product of the research will be to obtain a battery of putative biomarkers which will be useful tools within the field's arsenal to understand DBD risk, expression, and prevention. Capturing multiple hormones which interact with each other is innovative, with the potential to result in a "biosignature" of CU trait expression and DBD risk. This project will provide the foundation for a future program of research on biobehavioral mechanisms for DBD and CU traits, helping to bridge the gap between bench research and application to real-world issues facing adjudicated youth through interdisciplinary research. The investigative team is comprised new/early accomplished investigators and highly experienced mentors/consultants with decades of experience as interdisciplinary researchers. PUBLIC HEALTH RELEVANCE: Advancing understanding of the psychobiological mechanisms underlying risk for severe disruptive behavior disorders (DBD) is critical in order to prevent and treat DBD. The present proposal targets a novel population of girls with a very high range of DBD symptoms and problems, constituting one of the first investigations into their putative biomarkers. The study will have a large impact on the field because it employs multiple stress and sex hormones, raising the potential to reveal a unique biosignature of DBD in female adolescents. Behavioral manifestations of callous/ unemotional traits are specifically targeted as being neurobiologically informative for instantiating DBD risk. The present proposal parallels a recent investigation with incarcerated male adolescents to permit the exploration of sex similarities and differences.