Adult consequences of youth substance use: Twin study enriched for SUD risk

描述（由申请人提供）：青春期和成年初显期是一个重要的发展时期，在此期间，物质使用、误用和滥用伴随着神经认知发展、心理健康和社会环境的重要变化而发生，并对成人适应产生影响。现有的文献将青少年物质使用的影响与成人适应联系起来，证明了这些因素的重要性，但在很大程度上是相关的和横断面的，并且对它们的因果作用模棱两可。不良的成人适应可能是青少年滥用药物的结果，包括在这个敏感时期对大脑发育可能产生的神经毒性影响。然而，在物质使用开始之前存在的因素，如遗传倾向、反映遗传风险表现的预先存在的大脑异常、环境风险和共病，如儿童破坏性疾病（cdd），都会影响青少年物质暴露和成人结果。现有的研究通常没有考虑到这些因素。因此，即使是现存的少数纵向研究，它们所允许的推论也是有限的。我们建议扩展一项对453对双胞胎的前瞻性研究，首先在11岁时进行评估，以确定24岁时的青年成人结果。为了增加滥用药物的可能性，并确保高风险女性的充分代表，我们的社区双胞胎样本中有一半被富集为存在cdd；另一半是随机选择的，因此是明尼苏达州出生的双胞胎的代表。研究参与者完成了为期一天的个人摄入评估，包括物质使用、心理健康、整体调整、环境风险和保护因素、电生理测量、学业成绩和认知能力。参与者在14岁时重新接受评估，当时许多人开始使用药物，在17岁时再次接受评估，当时药物滥用变得明显。我们的样本目前的价值来自于已经收集到的大量数据，包括接触特定物质的时间、持续时间、频率和强度，以及我们对双胞胎在整个青春期的行为、环境和家庭特征的仔细评估。我们将利用这一样本的价值，对24岁的结果进行全面评估，广泛涵盖物质使用障碍、精神健康（包括持续性cdd）以及社会心理、电生理和神经心理结果。216对双胞胎的子样本也将进行MRI评估，增加了我们研究的独特性。我们的数据分析策略强调孪生差异设计的创新应用，这是一种强有力的方法，可以澄清由于物质使用而导致的影响，以及由于未测量的混杂因素（包括遗传因素）造成的影响。这种新颖的方法利用了双胞胎在成长过程中自然发生的药物滥用史的差异，使我们能够将药物滥用的影响与家庭和社会心理风险因素分开，这些因素早于药物暴露对他们的整体适应和成年后的大脑功能的影响。1

DESCRIPTION (provided by applicant): Adolescence and emerging adulthood represent an important developmental period during which substance use, misuse, and abuse occur concomitantly with important changes in neurocognitive development, mental health, and the social environment, with consequences for adult adjustment. Existing literature linking the effects of youth substance use to adult adjustment demonstrates the importance of these factors, but is largely correlational and cross-sectional, and leaves equivocal their causal role. Poor adult adjustment may be the result of youth substance misuse, including possible neurotoxic effects on brain development during this sensitive period. However, factors present prior to substance use initiation, such as genetic liability, pre- existing brain anomalies reflectng the manifestation of genetic risk, contextual risk, and comorbid disorders such as childhood disruptive disorders (CDDs), influence both adolescent substance exposure and adult outcomes. Existing research has typically not accounted for such factors. Thus, even the few longitudinal studies that exist are limited in the inferences they permit. We propose extending a prospective study of 453 twin pairs, first assessed at age 11, to determine young adult outcomes at age 24. To increase the likelihood that misuse of substances would be widespread and to ensure sufficient representation of high-risk females, half of our community-based twin sample was enriched for the presence of CDDs; the other half was selected at random and is thus representative of twins born in Minnesota. Study participants completed a day-long in- person intake assessment that included substance use, mental health, overall adjustment, environmental risk and protective factors, electrophysiological measurement, academic achievement, and cognitive ability. Participants were re-assessed at age 14, when many were initiating substance use, and again at age 17, when substance misuse was becoming apparent. Our sample's current value derives from the wealth of data already gathered on the timing, duration, frequency, and intensity of exposure to specific substances coupled with our careful assessments of the twins' behavioral, environmental, and familial characteristics throughout adolescence. We will capitalize on the value of this sample by undertaking a comprehensive assessment of age-24 outcomes that broadly covers substance use disorders, mental health (including persistence of CDDs), and psychosocial, electrophysiological, and neuropsychological outcomes. A subsample of 216 twin pairs will also undergo an MRI assessment, adding to the uniqueness of our study. Our data analytic strategy emphasizes the innovative application of a co-twin differences design, a powerful method for clarifying effects due to substance use from those due to unmeasured confounding factors, including genetic factors. This novel approach capitalizes on the differences in the history of substance misuse that occur naturally within twin pairs as they grow up, allowing us to separate the effects of substance abuse from familial and psychosocial risk factors that predate substance exposure on their overall adjustment and brain functioning as adults. 1