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见注意作为抑郁症的中间特征或内表型，来促进对儿童和青少年抑郁症发展的认识。阐明新的内在表型在青年将有助于增加知识的发展途径，抑郁症发起的遗传脆弱性。具体来说，成人研究结果表明，对情绪的偏见可能是遗传标记（例如，5-羟色胺转运体基因）和抑郁症（Beevers，Gibb，McGeary，&米勒，2007; Beevers，威尔斯，埃利斯，& McGeary，2009）。然而，迄今为止还没有研究将情绪信息加工作为青年人的内在表型。此外，研究青年抑郁症的发展尤为重要，因为抑郁症的发病与成年后复发的可能性增加2-7倍有关（Rutter，Kim-Cohen和Maughan，2006）。因此，为预防工作提供信息，重要的是在复发发作之前预测复发性抑郁症。抑郁症发展途径的研究与国家心理健康研究所的使命一致，即了解精神疾病的轨迹，以帮助确定何时，何地以及如何干预，以及NIMH主任托马斯因塞尔博士及其同事（2010年）关于利用遗传学和基因组数据识别精神疾病生物特征的研究领域标准（RDoC）。 临床相关电路行为模型（例如，注意力偏向于情绪）。此外，拟议的项目将针对NIMH发展转化研究部门的高优先级领域，通过1）识别反映维度过程的行为表型（即注意情绪刺激），这将有助于发现潜在的遗传脆弱性，2）测试一个模型，该模型将遗传学和个人行为特征纳入抑郁症的发展，3）采用纵向设计来研究抑郁的途径和抑郁增加的轨迹。此外，该提案旨在通过采用多方法，多知情人和多波设计来解决文献中关于注意力偏差作为抑郁症内在表型的重要空白，通过评估682名3年级，6年级和9年级学生的抑郁症诊断和症状，通过7波数据定期随访18个月来调查拥有这种内在表型的长期影响。此外，拟议中的研究将采用强大的方法来评估潜在的内表型的偏见注意情绪面孔，通过利用一个客观的措施，通过基于计算机的信息处理任务的偏见注意。最后，该研究将检查精心选择和理论动机的候选基因：5-羟色胺转运蛋白基因（5-HTTLPR），儿茶酚-O-甲基转移酶基因（COMT）和多巴胺D2受体基因（DRD 2）。这项研究将测试关于候选基因可能影响抑郁症的发展途径的先验假设。 公共卫生相关性：世界卫生组织指出，抑郁症占归因于非致命疾病的疾病负担的最大比例（Utsun & Chatterji，2001），并且许多个体在青春期期间经历他们的第一次临床显著抑郁症（Hankin等人，1998年）。此外，研究青少年期抑郁症的发展尤为重要，因为抑郁症发作与成年后复发的可能性增加2-7倍有关（Rutter，Kim-Cohen，& Maughan，2006）。因此，拟议的研究旨在研究青年抑郁症的发展途径，以便在复发事件发生之前为预防工作提供信息。

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. PUBLIC HEALTH RELEVANCE: The World Health Organization states that depression accounts for the greatest proportion of disease burden attributed to non-fatal illnesses (Utsun & Chatterji, 2001), and many individuals experience their first clinically significant depression during adolescence (Hankin et al., 1998). Furthermore, the study of the development of depression during adolescence 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, the proposed research aims to study developmental pathways to depression among youth to inform prevention efforts before recurrent episodes occur.