Developmental fMRI Study of Alcohol Use in Adolescence

描述（由申请人提供）：酒精的使用主要是在脆弱的发育时期开始的，此时白质束在前额皮质（PFC）内，以及PFC、前扣带、腹侧纹状体和边缘（情感）结构之间形成，突触发生显著修剪。这种神经元微调为执行认知和情绪调节功能的渐进式神经发育建立了支架，这些功能对情绪和行为自我控制至关重要。这一过程在青春期的脆弱性可以解释在有酒精使用问题的青少年和在青春期开始有慢性酒精使用史的成年人中发现的损害；青少年早期饮酒和大量间歇性饮酒可能导致长期的神经和行为发育后果。同样未知的是，与饮酒有关的一些神经发育迟缓和缺陷是否实际上早于饮酒，从而增加了滥用酒精的倾向。作为前驱疾病，它们可能特别容易因持续饮酒而进一步受损。到目前为止，还没有研究试图追踪神经发育的前体，以及这些过程中由于青春期不同程度的酒精使用而产生的变化。这项为期5年的前瞻性纵向fMRI研究旨在确定神经发育倾向的功能神经解剖学基础，以启动和升级酒精使用，并绘制青春期不同水平酒精使用导致的神经认知变化的进行性特征。实际上，这项研究还将从前体条件中分离出酒精使用的潜在剂量依赖性神经发育后果。酒精和毒品——“年轻的”11- 13岁的青少年将被预先筛选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饮酒的开始和不同程度的升级。将进行三次为期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志（例如，注意力不集中，冒险决策，情绪失调）与酒精，烟草和其他药物使用有关，从而为对酒精使用的开始和升级及其潜在影响的神经认知易感性因素的纵向调查奠定了基础(例如，Brown & Tapert, 2004； Fishbein等人，2005 5a,b； Giancola等人，1996；Sher et al., 1997；Tarter et al., 2004；Zeigler et al., 2005)。在所有分析中，将对同时使用烟草和其他药物、社会经济地位、智商、父母酗酒和吸毒以及其他相关协变量（如攻击性、酒精预期、关于酒精的规范信念、社会支持和偏差）进行调整。总的来说，这项研究有助于理解适应不良社会行为发展的潜在机制，这些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具体干预策略，从而改变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.