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，早期生活中的逆境是大脑健康发育和心理健康的普遍障碍。