Biological embedding of dimensional adversity: Developmental pathways toward psychopathology

从长远来看，早年的逆境是大脑健康发展和心理健康的普遍障碍。 令人担忧的是，早年遭遇逆境的情况非常普遍，近三分之二的人至少经历过 18岁之前的一次重大逆境事件。尽管数十年的研究记录了 这些早期经历对个人造成了身心损失，但仍然缺乏特异性 儿童逆境的亚型或维度如何传播特定的神经发展和心理模式 健康异常。近年来，维度方法导致了塑造领域的发现，从而共享 逆境的特征(例如，威胁、剥夺、不可预测性)可以用来使有意义的、特定于领域的 对发展结果的预测。这一系列调查的下一步是利用维度逆境 探索引发和推动逆境相关神经发育的生物后遗症的方法 瀑布。特别是青春期发育，已经被强调为一个候选的生物过程，既 对早期的逆境很敏感，发生在一个独特的可塑性发育窗口。青春期会引发一种 青春期激素的涌入，引起结构和功能神经发育的戏剧性变化，如 以及明显的生理和心理社会变化。即使在其他健康的发展背景下， 青少年患各种精神疾病的风险显著增加。到目前为止，早期的逆境已经 被证明有助于加速或保存与生存相关的资源的适应，包括移位 或者改变青春期发育。然而，逆境的特定维度如何调节青春期发育， 尤其是在性激素(如睾丸素、雌二醇)方面，其特征仍然较弱。 对早期逆境、青春期和神经发育之间的联系更是知之甚少，尽管最初的见解 已经表明青春期在传播增加风险的神经表型方面可能起到机械作用 治疗精神症状。我们新的初步结果强调了逆境亚型的具体影响 (例如，威胁暴露)以及青春期激素对大脑功能和结构的影响，在某些情况下 增加了青少年患精神病的风险。在目前的研究中，我们将把这些过程集成到一个 通过利用具有高度异质性逆境经历的高风险青年样本， 参加男孩城青少年关爱计划，调查逆境的不同方面如何影响 青春期和神经发育。为此，我们将使用最先进的逆境、神经成像和青春期 措施，包括性腺和肾上腺毛发激素分析(目标1)。拟议的研究将是 旨在测试逆境如何影响青春期过渡，并将提供对 神经生物学动力学，使个体发展成精神病理学(目标2)。考虑到青春期 开发是以延展性为标志的最重要的事件，这个项目有可能产生关于小说的见解 可促进童年逆境后健康神经发育轨迹的干预目标。

Early life adversity is a pervasive impediment to healthy brain development and mental health in the long term. Exposure to early life adversity is distressingly common, with nearly two-thirds of people experiencing at least one significant adversity event before the age of 18. Despite decades of research documenting the long-term physical and mental toll these early experiences have on individuals, there continues to be a lack of specificity in how subtypes or dimensions of child adversity propagate particular patterns of neurodevelopment and mental health aberrations. In recent years, dimensional approaches have led to field-shaping discoveries whereby shared features of adversity (e.g., threat, deprivation, unpredictability) can be used to make meaningful, domain-specific predictions about developmental outcomes. A next step in this line of inquiry is to use a dimensional adversity approach to probe the biological sequalae that initiate and propel adversity-related neurodevelopmental cascades. Pubertal development, specifically, has been highlighted as a candidate biological process that is both sensitive to early adversity and occurs in a uniquely plastic developmental window. Puberty induces a major influx of pubertal hormones that instigate dramatic changes in structural and functional neural development, as well as stark physical and psychosocial changes. Even in otherwise healthy developmental contexts, adolescents are at remarkably increased risk for a wide range of psychopathology. To date, early adversity has been shown to facilitate adaptations that accelerate or preserve resources related to survival, including shifted or altered pubertal development. However, how specific dimensions of adversity modulate pubertal development, particularly with respect to sex hormones (e.g., testosterone, estradiol), continues to be weakly characterized. Even less is known about links between early adversity, puberty, and neurodevelopment, although initial insights have indicated the possible mechanistic role puberty plays in propagating neuro-phenotypes that increase risk for psychiatric symptoms. Our novel preliminary results have highlighted specific effects of adversity subtypes (e.g., threat exposure) as well as pubertal hormones on brain function and structure, which in some cases amplified risk for psychopathology in adolescents. In the current study, we will integrate these processes into an overall framework by leveraging a high-risk sample of youth with highly heterogenous adversity experiences, enrolled from the Boys Town Youth Care program, to investigate how distinct dimensions of adversity affect puberty and neurodevelopment. To do so, we will use state-of-the-art adversity, neuroimaging, and pubertal measures, including gonadal and adrenarcheal hair hormone assays (Aim 1). The proposed study will be designed to test how adversity affects the pubertal transition and will provide fundamental insights into the neurobiological dynamics that prime individuals to develop psychopathology (Aim 2). Given that pubertal development is a paramount event marked by malleability, this project has the potential to yield insights on novel targets for intervention that could promote healthy neurodevelopmental trajectories following childhood adversity.