Developmental fMRI Study of Alcohol Use in Adolescence

描述(申请人提供)：酒精的使用主要开始于脆弱的发育年限，此时白质束在前额叶皮质(PFC)内以及PFC、前扣带回、腹侧纹状体和边缘(情感)结构之间形成树枝，并发生显著的突触修剪。这种神经元的微调为执行、认知和情绪调节功能的渐进性神经发展奠定了基础，这些功能对情绪和行为自我控制至关重要。青春期这一过程的脆弱性可以解释有酒精使用问题的青少年和从青春期开始就有长期饮酒史的成年人的损害；青春期早期饮酒和大量饮酒可能会导致长期的神经和行为发育后果。同样未知的是，与饮酒相关的一些神经发育迟缓和缺陷实际上是否早于饮酒，从而增加了滥用酒精的倾向。作为前驱条件，他们可能特别容易受到进一步的损害，以回应持续使用酒精。到目前为止，还没有研究试图跟踪神经发育的前体以及在整个青春期不同水平的酒精使用导致的这些过程的变化。拟议的为期5年的前瞻性纵向fMRI研究旨在确定启动和升级酒精使用的神经发育易感性的功能神经解剖学基础，并绘制由于青春期不同水平的酒精使用而导致的神经认知变化的进行性变化。这项研究还将有效地将酒精使用的潜在剂量依赖的神经发育后果与前体条件分开。酒精和毒品--11至13岁的青少年将预先筛查酒精问题的预测特征，以确保足够数量的青少年(最终n=154)在研究过程中表现出开始饮酒和不同程度的饮酒升级。将进行三波为期16个月的数据收集。在研究小组和其他人之前进行的研究中，发育缺陷和延迟的神经认知标记物(如注意力不集中、危险决策、情绪失调)与酒精、烟草和其他药物的使用有关，从而为纵向研究酒精使用开始和升级中的神经认知脆弱因素及其潜在影响奠定了基础(例如，Brown&Tapert，2004；Fishbein等人，2005a，b；Giancola等人，1996；Sher等人，1997；Tarter等人，2004；Zeigler等人，2005)。在所有分析中，将对同时使用烟草和其他药物、社会支持、智商、父母酗酒和吸毒以及其他相关协变量进行调整，如攻击性、酒精预期、关于酒精的规范信念、社会支持和越轨。总体而言，这项拟议的研究对于理解适应不良社会行为发展的潜在机制具有意义，这些社会行为增加了酒精开始和升级的风险，并提出了加强这些功能的干预措施的具体策略，从而改变了高危青少年的发展轨迹。

DESCRIPTION (provided by applicant): Alcohol use is primarily initiated during vulnerable developmental years when white matter tracts arborize within the prefrontal cortex (PFC), and between the PFC, anterior cingulate, ventral striatum and limbic (affective) structures, and significant synaptic pruning occurs. This neuronal fine-tuning establishes the scaffolding for the progressive neurodevelopment of executive cognitive and emotional regulatory functions that are critical for emotional and behavioral self-control. The vulnerability of this process in adolescence may explain findings of impairments in adolescents with alcohol use problems and in adults with a history of chronic alcohol use that began in adolescence; early alcohol use and heavy episodic drinking in adolescence may lead to long-term neural and behavioral developmental consequences. Also unknown is whether some of the neurodevelopmental delays and deficits associated with alcohol use actually predate use, thereby increasing propensity to misuse alcohol. And as precursor conditions, they may be particularly susceptible to further damage in response to the continued use of alcohol. No study to date has attempted to track neurodevelopmental precursors and the changes in these processes resulting from varying levels of alcohol use throughout adolescence. The proposed 5-year prospective longitudinal fMRI study seeks to identify functional neuroanatomical substrates of neurodevelopmental liability to initiate and escalate alcohol use and chart the progressive nature of neurocognitive change as a consequence of varying levels of alcohol use during adolescence. This study will also, in effect, isolate the potential dose-dependent neurodevelopmental consequences of alcohol use from precursor conditions. Alcohol and drug-"na¿ve" 11- to 13-year-olds will be prescreened for characteristics predictive of alcohol problems to ensure that a sufficient number of youth (final n=154) will exhibit initiation and varying levels of escalation of drinking during the course of the study. Three 16 month waves of data collection will be conducted. Neurocognitive markers of developmental deficits and delays (e.g., inattention, risky decision making, emotional dysregulation) have been associated with alcohol, tobacco, and other drug use in previous research conducted by the study team and others, thus laying the groundwork for a longitudinal investigation of neurocognitive vulnerability factors in initiation and escalation of alcohol use and its potential effects (e.g., Brown & Tapert, 2004; Fishbein et al., 2005a,b; Giancola et al., 1996; Sher et al., 1997; Tarter et al., 2004; Zeigler et al., 2005). In all analyses, adjustments will be made for concurrent use of tobacco and other drugs, SES, IQ, parental alcohol and drug abuse, and other relevant covariates, such as aggression, alcohol expectancies, normative beliefs about alcohol, social supports, and deviance. Overall, the proposed study has implications for understanding underlying mechanisms in the development of maladaptive social behaviors that increase risk for alcohol initiation and escalation and suggest specific strategies for interventions that strengthen these functions, thereby altering the developmental trajectory for at-risk adolescents.