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.

从长远来看，早期的逆境是对健康的大脑发育和心理健康的普遍障碍。 暴露于早期生命逆境是令人沮丧的，至少有近三分之二的人经历 18岁之前的一个重大逆境事件。尽管有数十年的研究记录了长期的研究 这些早期的经历对个人的身体和精神损害，仍然缺乏特殊性 在儿童逆境的亚型或维度如何传播神经发育和心理的特定模式中 健康畸变。近年来，维度的方法导致了现场成型发现，共享 逆境的特征（例如威胁，剥夺，不可预测性）可用于使特定于领域的特定领域 关于发展结果的预测。此询问线的下一步是使用维度逆境 探测启动和推动与逆境相关的神经发育的生物序列的方法 级联。特别是青春期开发已被强调为候选生物学过程 对早期逆境敏感，发生在独特的塑料发育窗口中。青春期引起了专业 涌入的青春期激素涌入，促使结构和功能神经发育的巨大变化 以及鲜明的身体和社会心理变化。即使在健康的发展环境中， 青少年对多种心理病理学的风险大大增加。迄今为止，早期的逆境有 被证明可以促进适应加速或保留与生存有关的资源，包括转移 或改变青春期的发展。但是，逆境的特定维度如何调节青春期的发展， 特别是关于性激素（例如，睾丸激素，雌二醇）的性激素，持续较弱的特征。 关于早期逆境，青春期和神经发育之间的联系的知之甚少，尽管最初的见解 已经表明青春期在传播风险的神经表现型中可能发挥的可能作用 用于精神病症状。我们新颖的初步结果突出了逆境亚型的特定影响 （例如，威胁暴露）以及关于大脑功能和结构的青春期激素，在某些情况下 在青少年中放大了心理病理的风险。在当前的研究中，我们将将这些过程整合到一个 总体框架通过利用具有高度异源逆境经历的高风险年轻人样本， 从男孩镇青年护理计划中注册，以调查逆境的不同维度如何影响 青春期和神经发育。为此，我们将使用最先进的逆境，神经影像和青春期 措施，包括性腺和肾上腺毛激素测定法（AIM 1）。拟议的研究将是 旨在测试逆境如何影响青春期过渡，并将提供基本的见解 神经生物学动力学是发展心理病理学的主要人物（AIM 2）。鉴于那个青春期 开发是以延展性为标志的最高事件，该项目有可能对新颖的见解产生见解 干预的目标，可以在儿童逆境之后促进健康的神经发育轨迹。