Hormones in Sex-different Developmental Psychopathology

描述（由申请人提供）：这是一份R-21提交，响应了将基础科学进展应用于临床问题的转化研究计划的需求。该项目将汇集一组经验丰富的基础科学家，他们是激素、行为和发育方面的专家，以及临床研究人员，他们在不同的分析水平上研究两种不同的临床综合征。临床领域的选择是基于它们明显不同的性别风险特征，并且因为在每个领域中，激素对疾病行为表达的调节都是假设的，但没有得到充分的研究：注意缺陷多动障碍（ADHD）和饮食失调（EDs）。该团队还将包括学习、注意力和认知动物模型方面的专家，以便研究行为表达背后的组成机制。该团队还包括对患有抑郁症的精神病患者进行激素研究的专家。许多科学家怀疑，环境激素干扰化学物质会以微妙的方式改变认知和身体发育。因此，该团队将拥有广泛的专业知识，旨在促进新的跨领域转化研究计划和优先排序，以促进连贯的转化研究议程的发展，该议程可以检查激素、激素干扰物和神经调节剂对多领域精神病理学行为表达的性别差异的贡献。这个广泛组成的小组将定期举行会议，以确保制定这一议程。此外，根据该奖项，将进行关键的试点研究，以检查(a)儿童、青少年和患有多动症的年轻成年男性和女性的认知和行为功能与循环激素的相关性，(b)在非临床人类样本中，饮食失调症状中青春期变化的激素调节，预期没有饮食干扰激素状态。(c)临床和非临床人类样本中背景污染物（多氯联苯和二氯二苯醚）暴露的认知和情感相关性，使用以前未应用于该问题的执行功能探针，以及(d)关键的动物实验，以评估激素效应是否可以解释先前在ADHD动物模型中观察到的学习性别差异。该奖项的预期成果是关于这些新颖研究方向的可行性和最有希望的领域的知识，伴随着一个连贯的转化研究议程，可以在额外的交叉研究计划中达到高潮。

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.