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）及其症状在男性中更为普遍，但在女性中呈上升趋势，其影响对女孩的身心健康和生活质量是毁灭性的。女性DBD的发病和上升通常表现在青春期，这是一个以激素剧烈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并不是巧合。提出的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，特别关注冷酷/无情的特征，作为一种重要的性格脆弱性，它可靠地预测了DBD的严重性和持久性。此外，神经生物学证据表明，应激和性激素与CU特征的表达有关，其中包括移情和麻木的神经回路的显著活动和调节。关于女性青少年DBD的研究很少，关于症状表达的生物行为机制的研究就更少了。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；当女性接受检查时，她们通常表现出轻度至中度的DBD症状和CU特征。目前的研究将对该领域产生重大影响，因为它针对的是具有一系列DBD症状和严重程度高的CU特征的未充分研究的女性人群。我们已获准在南橡树女子学校（Southern Oaks Girls School）检查压力和性激素，这是一家惩教机构，为威斯康星州最严重的青春期女性罪犯提供治疗。唾液将在两天内无创收集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。这种收集策略与最近在监禁男性青少年中进行的一项调查相类似，从而可以在不产生额外费用的情况下，对CU特征表达和DBD症状表达的生物行为机制中的性别相似性和性别差异进行探索性调查。该研究的最终成果将是获得一系列假定的生物标志物，这些生物标志物将成为该领域了解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一种创新，有可能导致CU特征表达和DBD风险的“生物特征”。该项目将为未来的DBD和CU特征的生物行为机制研究奠定基础，有助于通过跨学科研究弥合实验研究与实际问题之间的差距。调查团队由新/早期完成的调查员和具有数十年跨学科研究经验的经验丰富的导师/顾问组成。

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.