HPA Axis/ANS Function in Antisocial Pregnant Women and Effects on Their Offspring

描述（由申请人提供）：本R21申请的目的是探索关于母婴反社会行为障碍（ABD）传播的新假设。患有ABD的女性比其他母亲生下患有ABD的男孩和女孩的可能性高4-8倍。这项研究意义重大，因为它将促进对ABD母婴传播机制的了解，这是对社会产生重大负面影响的一组有害疾病研究中的一个未充分研究的重要空白。这些初步数据将通过下一步更大规模的纵向研究，为ABDs的预防研究开辟一条新的途径。我们的核心假设是基于预测适应反应假设。我们假设患有ABD的女性在怀孕期间有应激反应系统（SRS）功能减退，这使得后代的SRS功能减退，为后代提供了一个稳定、可预测和丰富的产后环境。相比之下，许多患有ABD的母亲只能提供一个混乱的产后环境，在最坏的情况下，对后代的破坏性明显。这种不匹配促进了不成熟、活动减退的SRS的持续存在，这是ABD男性和女性的特征。动物研究表明，在内源性SRS活动减退的环境中，出生后早期的大脑发育阻碍了抑制的发展，可以促进原始攻击的保持，并导致学习困难，所有这些都是早发性ABD的特征。我们的研究的影响是，对这组母亲的预防工作将发生实质性的变化。例如，预防工作可以在被确定患有ABD的母亲怀孕期间开始;目前的育儿计划在孩子上学时开始可能为时已晚。具体目标是：1）与无任何精神疾病（ND）的孕妇相比，描述患有ABD的孕妇的SRS（下丘脑垂体肾上腺（HPA）轴和自主神经系统（ANS））功能; 2）描述出生后前4个月内后代的SRS功能; 3）测试母体SRS功能作为母亲ABD与婴儿SRS功能减退之间关系的机制的冥想假设。为了实现这些目标，我们将对64名年龄在16-30岁之间的孕妇（50%患有ABD）及其4个月大的婴儿进行纵向研究，收集多个时间点的母亲和婴儿SRS功能的数据。本研究创新性地将预测适应反应假说应用于母婴ABD传播的临床问题，并测量SRS的两个组成部分。

DESCRIPTION (provided by applicant): The purpose of this R21 application is to explore a new hypothesis about the transmission of mother-child antisocial behavior disorders (ABDs). Women with ABDs are 4-8 times more likely than other mothers to have boys and girls who develop ABDs. This study is significant in that it will advance knowledge about mechanisms of mother-child transmission of ABDs, an understudied, important gap in research about a pernicious group of disorders that have major negative effects on society. These preliminary data will, through the next, larger longitudinal study, open up a new avenue of ABDs prevention research. Our Core Hypothesis is based on the Predictive Adaptation Response Hypothesis. We postulate that women with ABDs have stress response system (SRS) hypoactivity during pregnancy and that this programs SRS hypoactivity in the offspring, "preparing" the offspring for a postnatal environment that is stable, predictable, and rich in resources. In contrast, many mothers with ABDs are only able to provide a postnatal environment that is chaotic at best and overtly destructive to the offspring at worst. This mismatch promotes persistence of an immature, hypoactive SRS, which is characteristic of males and females with ABDs. Animal studies indicate that early postnatal brain development in an environment of endogenous SRS hypoactivity impedes the development of inhibition, can facilitate retention of primitive aggression, and result in learning difficulties, all characteristics of early onset ABDs. The impact of our study is that prevention work with this group of mothers would be substantially changed. For example, prevention work could begin during pregnancy in mothers identified as having ABDs; current parenting programs that start when children are in school may be too late. Specific Aims are to: 1) characterize SRS (hypothalamic pituitary adrenal (HPA) axis and autonomic nervous system (ANS)) function in pregnant women with ABDs, compared to pregnant women without any psychiatric disorder (ND); 2) characterize SRS function of offspring in the first 4 months of life; 3) test a meditational hypothesis of maternal SRS function as the mechanism for the relationship between ABDs in mothers and infant SRS hypoactivity. To accomplish these aims, we will conduct a longitudinal study of 64 pregnant women (50% with ABDs), ages 16-30 years, and their infants until they are 4 months old, collecting data about mother and then infant SRS function at multiple points in time. This study is innovative in applying the Predictive Adaptation Response Hypothesis to the clinical problem of mother-child ABDs transmission and in its approach of measuring both components of the SRS.