THE PRETERM BEHAVIORAL PHENOTYPE: TRAJECTORIES OF PSYCHOPATHOLOGY & CHANGES IN CEREBRAL CONNECTIVITY

项目总结：早产儿患精神疾病的风险较高，包括ADHD， 自闭症和焦虑症事实上，"早产儿行为表型"包括注意力不集中、焦虑和社交- 沟通障碍。这一系列共病疾病在整个生命周期中持续存在， 用于极早产儿（VPT;出生时妊娠≤ 32周）的长期损害和生活质量下降 儿童是大脑发育改变的高危人群。然而，潜在的神经生物学机制 这些症状的流行率增加仍不确定。此外，VPT儿童面临高暴露 有害的心理社会风险因素的发生率，这些因素同样与不良精神病结果有关 和大脑发育的变化。我们认为，连接性的降低， 关键功能网络内和跨关键功能网络的发展轨迹（例如，默认模式，额顶叶控制 和扣带-鳃盖网络）和相关的白色物质束（例如，扣带、胼胝体和钩） 是在9 - 10岁时持续存在或恶化的共病早产行为表型症状的基础。这个过程 从婴儿期开始，一直延续到童年中期，心理社会风险在其中起着重要的调节作用。 作用MRI方法学的进步现在能够表征结构和功能脑网络， 无与伦比的空间和时间分辨率。在这里，我们将这些高度创新的，最先进的核磁共振成像技术 技术与详细的精神病学评估，以研究我们独特的，社会人口多样化的纵向 VPT和足月出生的儿童（N = 302）队列，心理社会逆境率高，现在达到9 - 10岁。 该队列自出生以来一直受到随访，包括前瞻性收集高质量的新生儿功能和 结构连接性MRI数据和早产儿行为表型症状的纵向评估， 2岁和5岁时的心理社会和家庭因素，迄今为止在两个评估波的队列保持率> 80%。 对这一丰富队列的持续评价提供了一个机会，以确定：1）早产儿的轨迹 行为表型症状，以确定后期损害的早期指标，从而能够进行有针对性的干预，2） 新生儿和9 - 10岁的功能和结构连接与这些缺陷之间的关系，以及3） 心理社会逆境的修正作用。应用最先进的MRI采集和分析方法， 包括机器学习方法，能够前所未有地描述VPT出生对 大脑发育中的连接性。我们将扩展这些方法来描述成像之间的关系 措施和早产儿行为表型症状，提高对早期 生活暴露和心理社会风险对精神病结局的影响。这些数据对于发展个人至关重要- 不良心理健康水平的神经影像学、行为学和心理社会学症状前预测模型 结果，必要的措施，以告知和评估适用于敏感发育期间的治疗 这一时期可以减轻与早产和心理社会逆境相关的精神病理学风险。

PROJECT SUMMARY: Children born prematurely are at elevated risk for psychiatric disorders, including ADHD, autism and anxiety. Indeed, the ‘preterm behavioral phenotype’ is comprised of inattention, anxiety and social- communication impairments. This constellation of comorbid disorders persists across the lifespan, accounting for long-term impairment and diminished quality of life among very preterm (VPT; born ≤32 weeks gestation) children, a population at high risk for altered brain development. Yet, the neurobiological mechanisms underlying the increased prevalence of these symptoms remain undetermined. Further, VPT children face high exposure rates to deleterious psychosocial risk factors which have similarly been linked to adverse psychiatric outcomes and changes in brain development. We posit that decreased connectivity and the resulting diminished developmental trajectories within and across key functional networks (e.g., default mode, frontoparietal control and cingulo-opercular networks) and related white matter tracts (e.g., cingulum, corpus callosum and uncinate) underlie comorbid preterm behavioral phenotype symptoms that persist or worsen at age 9-10. This process begins during infancy and extends to middle childhood, with psychosocial risk playing an important modifying role. Advances in MRI methodology now enable characterization of structural and functional brain networks with unparalleled spatial and temporal resolution. Here, we couple these highly innovative, state-of-the-art MRI techniques with detailed psychiatric assessments to study our unique, sociodemographically-diverse longitudinal cohort of VPT and term-born children (N=302) with high rates of psychosocial adversity now reaching age 9-10. The cohort has been followed since birth, including prospective collection of high-quality neonatal functional and structural connectivity MRI data and longitudinal assessments of preterm behavioral phenotype symptoms and psychosocial and familial factors at ages 2 and 5, with >80% cohort retention to date at both assessment waves. Continued evaluation of this enriched cohort provides an opportunity to determine: 1) trajectories of preterm behavioral phenotype symptoms to define early indicators of later impairment enabling targeted interventions, 2) relationships between neonatal and age 9-10 functional and structural connectivity and these deficits, and 3) the modifying role of psychosocial adversity. Application of cutting-edge MRI acquisition and analysis methods, including machine learning approaches, enables unprecedented characterization of the effects of VPT birth on connectivity in the developing brain. We will extend these methods to delineate relationships between imaging measures and preterm behavioral phenotype symptoms, improving understanding of modifiable effects of early life exposures and psychosocial risk on psychiatric outcomes. These data are critical for developing individual- level neuroimaging, behavioral and psychosocial presymptomatic predictive models for adverse mental health outcomes, measures necessary to inform and evaluate treatments applicable during sensitive developmental periods which mitigate risks of psychopathology associated with prematurity and psychosocial adversity.