Biological embedding of dimensional adversity: Developmental pathways toward psychopathology

维度逆境的生物嵌入：精神病理学的发展途径

• 批准号: 10928974
• 负责人: Giorgia Picci
• 金额: $ 25.46万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10928974
• 关键词: Acceleration; Adolescent; Affect; Age; Biological; Biological Assay; Biological Process; Brain; Caring; Child; Childhood; Development; Dimensions; Distress; Enrollment; Estradiol; Event; Exposure to; Gonadal Steroid Hormones; Hair; Hormones; Individual; Intervention; Link; Measures; Mental Health; Neurobiology; Outcome; Pathway interactions; Pattern; Persons; Play; Process; Psyche structure; Psychopathology; Puberty; Research; Resources; Risk; Role; Sampling; Shapes; Specificity; Structure; Testing; Testosterone; Youth; boys; brain health; childhood adversity; deprivation; design; developmental plasticity; early experience; early life adversity; experience; high risk; insight; neurodevelopment; neuroimaging; novel; preservation; programs; psychiatric symptom; psychosocial; puberty transition

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.

早期生活逆境是长期健康大脑发育和心理健康的普遍障碍。 暴露于早期生活逆境是令人沮丧的普遍现象，近三分之二的人至少经历过 在18岁之前经历过一次重大的逆境。尽管数十年的研究记录了 这些早期经历对个人造成的身心伤害，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育和心理模式 健康失常近年来，维度方法导致了场形发现， 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，特定领域的 预测发展结果。这一系列研究的下一步是使用维度逆境 探索启动和推动逆境相关神经发育的生物学后遗症的方法 瀑布青春期的发展，特别是，已被强调为候选生物过程，这既是 对早期逆境敏感，发生在一个独特的可塑性发育窗口。青春期会导致 青春期激素的涌入，引起结构和功能神经发育的巨大变化，如 以及生理和心理上的巨大变化即使在其他健康的发展背景下， 青少年患各种精神病理学的风险显著增加。到目前为止，早期的逆境 已被证明可以促进适应，加速或保护与生存有关的资源，包括转移 或者青春期发育改变然而，逆境的具体方面如何调节青春期的发展， 特别是关于性激素（例如，睾酮、雌二醇）的特征仍然很弱。 关于早期逆境、青春期和神经发育之间的联系，人们所知更少，尽管最初的见解 已经指出，青春期在传播增加风险的神经表型中可能起着机械作用。 精神病症状我们新的初步结果强调了逆境亚型的特定影响 (e.g.,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， 增加青少年精神病的风险。在目前的研究中，我们将把这些过程整合到一个 通过利用具有高度异质性逆境经历的高风险青年样本， 从男孩镇青年关怀计划招收，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 测量，包括性腺和肾上腺毛激素测定（目的1）。拟议的研究将 旨在测试逆境如何影响青春期的过渡，并将提供基本的见解， 神经生物学动力学促使个体发展为精神病理学（目标2）。考虑到青春期 发展是一个以可塑性为标志的最重要的事件，这个项目有可能产生对小说的见解。 干预目标可以促进儿童逆境后健康的神经发育轨迹。