Hormones in Sex-different Developmental Psychopathology

描述(由申请人提供)：这是一份R-21意见书，回应了将基础科学进展应用于临床问题的转化性研究计划的需要。该项目将汇集一支经验丰富的基础科学家团队，他们是激素、行为和发育方面的专家，临床研究人员在不同的分析水平上研究两种不同的临床综合征。临床领域的选择是因为他们明显不同的性风险特征，因为对于每个领域，激素对疾病行为表达的调节已经被假设，但没有得到很好的研究：注意力缺陷多动障碍(ADHD)和饮食障碍(EDS)。该团队还将包括学习、注意力和认知的动物模型方面的专业知识，以便可以检查行为表达的组成部分机制。该团队还包括对患有抑郁症的精神人群进行荷尔蒙研究的专业知识。许多科学家怀疑环境荷尔蒙干扰化学物质会以微妙的方式改变认知和身体发育，在这方面也有专门知识。因此，该团队将拥有广泛的专业知识，旨在促进新的交叉翻译研究规划和优先顺序，以促进连贯的翻译研究议程的发展，该议程可以检查荷尔蒙和激素干扰物和神经调节剂对多个领域精神病理学行为表达的性别差异的贡献。这个组成广泛的小组将定期举行会议，以确保这一议程的发展。此外，根据该奖项，将进行关键的试点研究，以检查(A)患有ADHD的儿童、青少年和年轻成年男性和女性认知和行为功能的循环激素相关性，(B)在非临床人类样本中对进食障碍症状青春期变化的激素调节，预计不会对激素状态造成饮食干扰，(C)使用以前未应用于该问题的执行功能探测器，在临床和非临床人类样本中检测背景污染物(多氯联苯和DDE)暴露的认知和情感相关性，以及(D)关键的动物实验，以评估荷尔蒙效应是否可以解释先前观察到的ADHD动物模型在学习方面的性别差异。该奖项的预期成果是关于这些新的研究方向的可行性和最有希望的领域的知识，并伴随着一个连贯的翻译研究议程，可以最终导致更多的交叉研究倡议。

DESCRIPTION (provided by applicant): This is an R-21 submission that responds to the need for translational research initiatives to apply basic science advances to clinical problems. The project would bring together a team of experienced basic scientists who are experts in hormones, behavior, and development with clinical researchers who study two different clinical syndromes at different levels of analysis. The clinical domains were selected for their distinctly different sex-risk profiles, and because for each domain hormone modulation of the disorder's behavioral expression has been hypothesized but not well-investigated: attention-deficit hyperactivity disorder (ADHD) and eating disorders (EDs). The team would also include expertise in animal models of learning, attention, and cognition, so that component mechanisms underlying behavioral expression can be examined. The team also includes expertise in hormone studies of psychiatric populations with depression. Expertise is also present in environmental hormone disrupting chemicals that are suspected by many scientists of altering cognitive and physical development in subtle ways. Thus, the team will have broad expertise that is designed to foster novel cross-cutting translational research planning and prioritizing in order to foster development of a coherent translational research agenda that can examine the contribution of hormones and hormone disruptors and neuromodulators to sex differences in behavioral expression of psychopathology in multiple domains. Regular meetings of this broadly composed team would be held to assure development of this agenda. In addition, under the award, key pilot studies will be conducted to examine (a) circulating hormonal correlates of cognitive and behavioral functioning in children, adolescents, and young adult males and females with ADHD, (b) hormone moderation of pubertal changes in eating disorder symptoms in a non-clinical human sample expected to be free of dietary disruption of hormonal status, (c) cognitive and affective correlates of background contaminant (PCB and DDE) exposures in clinical and non-clinical human samples using executive function probes not previously applied to this question, and (d) key animal experiments to evaluate whether hormonal effects can explain previously-observed sex differences in learning in animal models of ADHD. Expected outcomes of the award are knowledge about the feasibility and areas of greatest promise for these novel research directions, accompanied by a coherent translational research agenda that can culminate in additional cross-cutting research initiatives.