Early Stress, Sensitive Periods and the Neurobiology of Addiction

描述（由申请人提供）：童年虐待（即父母、同伴或兄弟姐妹的身体、性或情感虐待，身体和情感忽视）对药物滥用和依赖的风险有巨大的影响。不良童年经历研究报告称，暴露于与虐待有关的逆境中占药物滥用人口归因风险的64%。了解这种联系可能对我们预防、预防或治疗药物滥用的努力至关重要。在上一个资助期间，我们进行了一系列研究，以更好地了解儿童虐待与药物使用之间的关系。我们在横断面研究中发现，暴露于身体虐待是高水平药物和酒精使用比情感虐待更重要的危险因素，并且身体虐待（但不是情感虐待）与上升多巴胺系统主要成分的t2 -松弛时间（通过MRI评估的脑血容量的间接测量）的显着改变有关。两个成分（背外侧前额叶和前扣带皮层）的t2 -松弛时间与药物和酒精使用程度相关。此外，我们发现在身体虐待的受试者中，小脑蚓部第一小叶（舌）的大小与物质使用程度之间存在很强的统计关系。我们还发现，受虐待者的药物使用在20-21岁时激增。本研究的主要目的是在一项前瞻性研究中检验被虐待者背外侧前额叶和前扣带皮层的t2 -松弛时间和大舌尺寸是否可以预测被虐待者的药物和酒精使用程度。此外，我们将检验以下假设：遭受虐待的类型和时间很重要，在某些敏感时期，遭受特定类型的虐待最有可能影响这些大脑区域的发育，并增加滥用药物的风险。通过从发育神经科学的角度研究这一现象，这一信息将为我们理解虐待与药物滥用之间的关系提供新的线索。这些研究可能为设计在儿童最脆弱时期保护儿童的方案提供必要的关键见解，并在暴露的个体的脆弱性变得明显之前制定先发制人的策略来帮助他们。

DESCRIPTION (provided by applicant): Childhood maltreatment (i.e., physical, sexual or emotional abuse by parents, peers or siblings, physical and emotional neglect) has an enormous impact on risk for substance abuse and dependence. The Adverse Childhood Experience Study reported that exposure to maltreatment-related adversity accounted for 64% of the population attributable risk for substance abuse. Understanding this association may be crucial to our efforts to prevent, preempt or treat drug abuse. During the previous funding period we conducted a series of studies to better understand the association between childhood maltreatment and substance use. We found in cross-sectional studies that exposure to physical maltreatment was a more significant risk factor for high levels of drug and alcohol use than emotional maltreatment, and that physical maltreatment (but not emotional maltreatment) was associated with marked alterations in T2-relaxation time (an indirect measures of cerebral blood volume assessed by MRI) in major components of the ascending dopamine system. T2-relaxation time in two components (dorsolateral prefrontal and anterior cingulate cortex) correlated with degree of drug and alcohol use. Further we found a strong statistical relationship between the size of the first lobule (lingula) of the cerebellar vermis in physically maltreated subjects and degree of substance use. We also found that substance use by maltreated individuals spiked at 20-21 years of age. The key aims of the proposed study are to test in a prospective study whether T2-relaxation time in dorsolateral prefrontal and anterior cingulate cortex, and large lingula size can predict degree of drug and alcohol use by maltreated individuals. Moreover, we will test the hypothesis that type and timing of exposure to maltreatment matters, and that there are sensitive periods when exposure to specific types of maltreatment are most likely to effect the development of these brain regions¿ and to increase risk for drug abuse. This information will shed new light on our understanding of the relationship between maltreatment and drug abuse by examining the phenomenon from a developmental neuroscience perspective. These studies may provide the critical insights necessary to design programs to protect children during their most vulnerable periods, and to develop preemptive strategies to aid exposed individuals before their vulnerability becomes manifest.