Effects of Prenatal Alcohol Exposure on the Neurobiology of Social Behavior

胎儿酒精谱系障碍（FASD）是一个总括性术语，指的是神经行为的连续性， 以及母亲怀孕期间饮酒造成的生理损伤。在认知上， 与产前酒精暴露（PAE）相关的生理和行为障碍， 临床和临床前文献，终身社会行为缺陷作为一个统一的特点，在整个 胎儿酒精谱系障碍（FASD）FASD患者的社会行为受损 对其他领域的广泛影响，并可能导致学校环境、社会 拒绝，法律纠纷，以及后来的心理健康问题。PAE相关的社会行为缺陷出现 在发展的早期，在青春期之前和期间变得更加明显，这是一个关键时期， 发育，在此期间发生重大的行为，认知和生理变化，包括发病， 青春期，使青春期成为一个独特的时期，增加脆弱性的社会行为功能障碍。然而，在这方面， 由于FASD和其他儿童期疾病的特征与社会因素有相当大的重叠， 行为障碍-包括自闭症谱系障碍（ASD）-达到明确的诊断， 临床社区的挑战。事实上，有人认为， 受FASD影响的人的死亡率已经导致低估了其在普通人群中已经很高的患病率（2-5%）。 目前研究建议的相关性取决于建立一个更具体的社会 神经行为特征，可以支持早期诊断和更多的具体策略的发展 对FASD进行有针对性的干预。以前的临床前和临床研究表明，PAE影响大脑区域， 并改变支持社会行为的神经递质，包括前额皮质，杏仁核， 下丘脑，以及催产素和加压素神经递质系统。因此，本 一项提案将使用一种成熟的动物来描述社会行为及其潜在的神经相关性 中度PAE模型。我们将检验PAE导致社会行为障碍（目标1）的假设， OT/AVP系统的改变的发展（目的2）。此外，由于临床和临床前 文献支持催产素治疗在增强健康个体的社会行为方面的作用， 以及改善与ASD、额颞叶痴呆和精神分裂症相关的社会行为缺陷， 我们还建议调查催产素管理作为挽救社会行为缺陷的干预措施 目标3（Aim 3）拟议的研究将提供进一步的深入了解机制的影响 的PAE的社会行为，并建议可能的方法，为衰减这种赤字。

Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that refers to the continuum of neurobehavioral and physiological impairments resulting from maternal alcohol consumption during pregnancy. Of the cognitive, physiological and behavioral impairments associated with prenatal alcohol exposure (PAE) documented in the clinical and pre-clinical literature, lifelong social behavior deficits serve as a unifying feature across the entire continuum of Fetal Alcohol Spectrum Disorders (FASD). Impaired social behavior in individuals with FASD has widespread implications for other domains and may contribute to difficulties within the school environment, social rejection, trouble with the law, and later mental health problems. PAE-related social behavior deficits emerge early in development and become more pronounced prior to and during adolescence, a critical period of development during which significant behavioral, cognitive, and physiological changes occur, including onset of puberty, making adolescence a unique period of increased vulnerability to social behavior dysfunction. However, because of the considerable overlap in the characteristics of FASD and other childhood disorders with social behavior impairments – including autism spectrum disorder (ASD) – reaching a definitive diagnosis presents a challenge for the clinical community. Indeed, it has been suggested that the difficulty in identifying individuals affected by FASD has led to an underestimation of its already high prevalence (2-5%) in the general population. The relevance of the current research proposal relies on the need for establishing a more specific social neurobehavioral profile that could support the development of specific strategies for earlier diagnoses and more targeted interventions for FASD. Previous pre-clinical and clinical research suggests that PAE affects brain areas and alters neurotransmitters shown to support social behavior, including the prefrontal cortex, amygdala, and hypothalamus, as well as the oxytocin and vasopressin neurotransmitter systems. Accordingly, the present proposal will characterize social behavior and its underlying neural correlates using a well-established animal model of moderate PAE. We will test the hypothesis that PAE results in social behavior impairments (Aim 1) that result from altered development of the OT/AVP systems (Aim 2). In addition, because the clinical and preclinical literature support a role for oxytocin treatment in enhancing aspects of social behavior in healthy individuals as well as in ameliorating social behavior deficits associated with ASD, frontotemporal dementia, and schizophrenia, we also propose to investigate oxytocin administration as an intervention for rescuing social behavior deficits following PAE (Aim 3). The proposed studies will provide further insight into mechanisms underlying the effects of PAE on social behavior, and suggest possible approaches for attenuation of such deficits.