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

反社会孕妇的 HPA 轴/ANS 功能及其对其后代的影响

• 批准号: 8234587
• 负责人: KATHLEEN Ann PAJER
• 金额: $ 16.7万
• 依托单位: IWK HEALTH CENTRE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-16 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8234587
• 关键词: Accounting; Adverse event; Age; Aggressive behavior; Alcohol or Other Drugs use; Animals; Antisocial Personality Disorder; Autonomic nervous system; Behavior Disorders; Behavioral; Brain; Characteristics; Child; Clinical; Clinical Research; Conduct Disorder; Data; Development; Disease; Early treatment; Environment; Environmental Risk Factor; Etiology; Exposure to; Female; Fetus; Foundations; Genetic; Goals; Heritability; Infant; Intervention; Investigation; Knowledge; Learning; Life; Link; Longitudinal Studies; Measures; Mediating; Mental disorders; Modeling; Mother-Child Relations; Mothers; Nervous System Physiology; Parenting behavior; Patients; Phenotype; Prefrontal Cortex; Pregnancy; Pregnant Women; Preparation; Prevention; Prevention Research; Preventive; Primary Prevention; Research; Resources; Schools; Smoking; Societies; System; Testing; Time; Woman; Work; anti social; base; biological adaptation to stress; boys; developmental plasticity; disorder prevention; early onset; girls; high risk; hypothalamic-pituitary-adrenal axis; innovation; male; maternal depression; maternal stress; novel; offspring; postnatal; pregnant; programs; response; transmission process

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. PUBLIC HEALTH RELEVANCE: This R21 application explores a new hypothesis about the mother-child transmission of antisocial behavior disorders. We hypothesize that mothers with antisocial behavior disorders have hypoactive stress response systems when they are pregnant and that this programs stress response system hypoactivity in the offspring. This hypoactivity in the infants could then facilitate the development of later antisocial behavior disorders.

描述（由申请人提供）：本R21申请的目的是探索一种关于母子间反社会行为障碍（ABDs）传播的新假设。患有abd的女性生下患有abd的男孩和女孩的可能性是其他母亲的4-8倍。这项研究具有重要意义，因为它将推进对ABDs母婴传播机制的了解，这是对一组对社会产生重大负面影响的有害疾病的研究中一个未被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，开辟ABDs预防研究的新途径。我们的核心假设是基于预测性适应反应假设。我们假设患有ABDs的女性在怀孕期间有应激反应系统（SRS）的低活性，这使得后代的SRS低活性，为后代的产后环境做了“准备”，这个环境是稳定的，可预测的，资源丰富的。相比之下，许多患有abd的母亲只能提供一个最好的混乱的产后环境，最坏的情况是对后代造成明显的破坏。这种不匹配促进了不成熟、低活性的SRS的持续存在，这是男性和女性ABDs的特征。动物研究表明，在内源性SRS低活性的环境下，出生后早期的大脑发育会阻碍抑制的发展，促进原始攻击的保留，并导致学习困难，这些都是早发性ABDs的特征。我们研究的影响是，针对这群母亲的预防工作将发生重大变化。例如，预防工作可以在确定患有ABDs的母亲怀孕期间开始；目前在孩子上学时开始的育儿计划可能太晚了。具体目的是：1)比较ABDs孕妇与无精神障碍孕妇的SRS（下丘脑-垂体-肾上腺（HPA）轴和自主神经系统（ANS））功能；2)表征子代出生后4个月的SRS功能；3)检验母亲SRS功能作为母亲ABDs与婴儿SRS低活动之间关系机制的冥想假设。为了实现这些目标，我们将对64名16-30岁的孕妇（50%患有ABDs）及其婴儿进行纵向研究，直到他们4个月大，收集多个时间点的母亲和婴儿SRS功能数据。本研究在将预测性适应反应假说应用于母婴ABDs传播的临床问题以及测量SRS两个组成部分的方法方面具有创新意义。