Biased Attention to Emotional Faces as an Endophenotype Predicting Depression

描述（由申请人提供）：本提案的总体目标是通过调查对情绪刺激的偏向性注意作为抑郁症的中间特征或内表型，来提高对儿童和青少年抑郁症发展的认识。阐明青少年新的内表型将有助于增加对由遗传脆弱性引发的抑郁症的发育途径的了解。具体来说，成人研究结果表明，对情绪的偏向性注意可能是遗传标记（如血清素转运基因）和抑郁症之间的一种内表型（Beevers, Gibb, McGeary, & Miller, 2007; Beevers, Wells, Ellis, & McGeary, 2009）。然而，到目前为止，还没有研究将情绪的信息处理作为青少年的一种内表型。此外，考虑到青少年发病的抑郁症与成年后复发的可能性增加2-7倍相关，对青少年抑郁症发展的研究尤为重要（Rutter, Kim-Cohen, & Maughan, 2006）。因此，重要的是在青少年抑郁复发之前预测青少年抑郁的发生。对抑郁症发展途径的研究与美国国家心理健康研究所的使命是一致的，即了解精神疾病的发展轨迹，帮助确定何时、何地、如何干预，以及NIMH主任托马斯·因塞尔博士和他的同事（2010）的研究领域标准（RDoC）关于利用遗传学和遗传学数据识别精神疾病的生物特征的需要

DESCRIPTION (provided by applicant): The overall goal of this proposal is to advance knowledge on the development of depression in children and adolescents by investigating biased attention to emotional stimuli as an intermediate trait, or endophenotype, for depression. Elucidating novel endophenotypes in youth will help to increase knowledge on developmental pathways to depression initiated by genetic vulnerabilities. Specifically, adult findings suggest that biased attention to emotion may be an endophenotype between genetic markers (e.g., serotonin transporter gene) and depression (Beevers, Gibb, McGeary, & Miller, 2007; Beevers, Wells, Ellis, & McGeary, 2009). Yet, no study to date has examined information processing of emotion as an endophenotype among youth. Furthermore, the study of the development of depression among youth is especially important given that adolescent-onset depression is associated with a 2-7 times increased likelihood of recurrence in adulthood (Rutter, Kim-Cohen, & Maughan, 2006). Therefore, to inform prevention efforts it is important to predict adolescent-onset depression before recurrent episodes occur. The study of developmental pathways to depression is consistent with the mission of the National Institute of Mental Health to understand trajectories of mental illness that can help determine when, where, and how to intervene as well as Director of NIMH Dr. Thomas Insel and colleagues' (2010) research domain criteria (RDoC) regarding the need for identifying biosignatures of mental illness utilizing data from genetics and clinically relevant circuitry-behavior models (e.g., attention bias to emotion). In addition, the proposed project will target the NIMH Division of Developmental Translational Research areas of high priority by 1) identifying behavioral phenotypes reflecting dimensional processes (i.e. attention to emotional stimuli) that will help to discover underlying genetic vulnerabilities, 2) testing a model that incorporates genetics and individual behavioral characteristics in the development of depression, and 3) employing a longitudinal design to examine pathways for depression and trajectories of increasing depression. Additionally, this proposal seeks to address important gaps in the literature on attention bias as an endophenotype of depression by employing a multi-method, multi-informant, and multi-wave design to investigate the long-term effects of possessing this endophenotype by assessing depression diagnoses and symptoms among 682 3rd, 6th, and 9th graders across 7 waves of data with regular follow-ups over a period of 18 months. Moreover, the proposed research will employ strong methodology to assess the potential endophenotype of biased attention to emotional faces by utilizing an objective measure of biased attention via a computer based information processing task. Finally, the research will examine carefully selected and theoretically motivated candidate genes: the serotonin transporter gene (5-HTTLPR), catechol-o- methyl-transferase gene (COMT), and dopamine D2 receptor gene (DRD2). The research will test clear a priori hypotheses about the developmental pathways through which candidate genes may influence depression.