Overgeneral autobiographical memory: Genetic mechanisms and contributing factors

描述（由申请人提供）：总体自传体记忆（Overgeneral autobiographical memory， OGM）已成为理解抑郁症病因、现象学和病程的重要现象，它确实可能是抑郁症发病和病程的一个易感因素。然而，对影响OGM的某些因素缺乏认识。具体来说，主要问题仍未解决，包括：1)导致OGM的机制以及它们如何相互作用；2)可能对OGM及其途径产生的分子遗传影响。此外，OGM影响抑郁症的潜在机制，无论是独立的还是通过它们对OGM的影响，在多大程度上是未知的。本提案旨在利用一项正在进行的关于焦虑和单相情绪障碍风险因素的8年纵向前瞻性研究的数据来解决这些问题。虽然对OGM背后的机制进行检查并不是更大规模调查的目的，但由于其他原因，正在对提议的机制采取措施，并正在收集DNA。拟议的研究将对最近的CaR-FA-X模型进行实证测试，该模型提出了可能构成OGM的三种机制：捕获和反刍、功能性回避和执行控制受损（Williams et al., 2007）。结构方程模型（SEM）将用于研究这些提出的机制对OGM（单独和相互作用）和抑郁（直接和间接通过它们对OGM的影响）的贡献程度。此外，OGM与几个候选基因之间的关系将被研究，这些候选基因被选择为抑郁和记忆过程的理论相关性。如果检测到显著的关联，那么扫描电镜将用于检查相关基因如何与CaR-FA-X模型的机制相关。培训活动包括：1)完成遗传学、扫描电镜、人类记忆和认知以及人类神经心理学的课程；2)参加扫描电镜、分子生物学和生物标志物研究的夏季研讨会；3)咨询OGM研究、统计学和遗传学领域的专家。这些经验将为完成拟议的项目和未来关于抑郁症风险因素的交叉研究提供坚实的基础。提出的研究将提供经验证据，可以为当前的理论模型和后续的研究提供信息，这是抑郁症的风险因素。这些发现也可能对抑郁症的临床治疗有启示，因为了解OGM的机制及其对抑郁症的影响，可以为干预提供信息。此外，研究OGM与遗传风险因素之间的关系可能会增加对基因如何赋予抑郁症的责任的理解，并进一步发展现有的抑郁症生物学和行为指标的综合概况。

DESCRIPTION (provided by applicant): Overgeneral autobiographical memory (OGM) has emerged as an important phenomenon for understanding the etiology, phenomenology, and course of depression, and it indeed may represent a vulnerability factor for the onset and course of depression. However, knowledge is lacking about certain factors that influence OGM. Specifically, major questions remain unresolved regarding 1) the mechanisms that contribute to OGM and how they may interact, and 2) the possible molecular genetic influences on OGM and their pathways. Furthermore, the extent to which the mechanisms underlying OGM impact depression, either independently or through their effect on OGM, is unknown. This proposal aims to address these issues using data from an ongoing 8-year longitudinal prospective study of risk factors for anxiety and unipolar mood disorders. Although an examination of the mechanisms underlying OGM was not an aim of the larger investigation, measures of the proposed mechanisms are being administered for other reasons, and DNA is being collected. The proposed study will conduct an empirical test of the recent CaR-FA-X model that presents three mechanisms that may underlie OGM: capture and rumination, functional avoidance, and impaired executive control (Williams et al., 2007). Structural equation modeling (SEM) will be used to investigate the degree to which these proposed mechanisms contribute to both OGM (alone and in interaction) and depression (both directly and indirectly through their effect on OGM). Furthermore, the relationship between OGM and several candidate genes selected for their theoretical relevance to depression and memory processes will be investigated. If significant associations are detected, then SEM will be used to examine how the relevant genes may relate to the mechanisms of the CaR-FA-X model. Training activities include 1) the completion of course work in genetics, SEM, human memory and cognition, and human neuropsychology, 2) participation in summer workshops on SEM, molecular biology, and biomarker research, and 3) consultation with experts in the fields of OGM research, statistics, and genetics. These experiences will provide a strong foundation for the completion of both the proposed project and future cross-cutting research on risk factors for depression. The proposed research will provide empirical evidence that can inform current theoretical models and subsequent studies of this proposed risk factor for depression. The findings may also have implications for the clinical treatment of depression, as knowledge of the mechanisms that underlie OGM, and their effects on depression, could inform interventions. In addition, research on the relationship between OGM and genetic risk factors may increase understanding of how genes confer liability to depression, and further develop existing integrative profiles of biological and behavioral indicators of depression. PUBLIC HEALTH RELEVANCE: An empirical investigation of the mechanisms of overgeneral autobiographical memory (OGM) may have important implications for the study and treatment of depression. Greater knowledge of the biological and behavioral markers underlying OGM-a proposed risk factor for depression-has implications for understanding the etiology and course of depression. Additionally, such knowledge may inform existing treatments for depression by identifying additional targets for intervention.