Genetic Associations with Biased Processing of Emotion Cues in MDD

MDD 中情绪线索加工偏差的遗传关联

• 批准号: 7497977
• 负责人: CHRISTOPHER G BEEVERS
• 金额: $ 26.55万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-19 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497977
• 关键词: Address; Adult; Affective; Alleles; Arts; Attention; Catechol O-Methyltransferase; Cognitive; Cues; Data; Depressed mood; Diagnosis; Disease; Disease model; Dopamine; Emotional; Emotions; Etiology; Eye; Gene Frequency; Genes; Genetic; Genetic Markers; Genetic Models; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Individual; Knowledge; Maintenance; Major Depressive Disorder; Measures; Minor; Modeling; Mood Disorders; Moods; Neurobiology; Other Genetics; Pathway interactions; Patient Self-Report; Pharmacological Treatment; Phenotype; Play; Process; Psychopathology; Research; Research Personnel; Risk; Risk Factors; Role; Serotonin; Specificity; Stimulus; System; Testing; Thinking; Tryptophan 5-monooxygenase; Variant; Work; base; clinically relevant; design; dysphoria; emotional stimulus; genetic association; genetic variant; negative mood; programs; psychosocial; serotonin transporter; theories; translational study; treatment program

DESCRIPTION (provided by applicant): Major Depressive Disorder (MOD) is one of the most prevalent psychiatric problems faced by U.S. adults. Although MOD appears to be highly heritable, genetic association studies for this disorder have been variable and equivocal. Identifying intermediate phenotypes may be crucial for advancing our understanding of MDD. Neurobiological models suggest that genetic variants of the serotonin transporter (5-HTTLPR) play a crucial role within a widely distributed and interconnected system of cortical and subcortical pathways that regulate processing of emotion cues. Some researchers have speculated that serotonergic polymorphisms increase the risk for and maintenance of affective disorders by contributing to altered processing of emotional stimuli. Our primary aim is to use a state-of-the-art eye tracking paradigm to examine whether polymorphisms of the 5-HTTLPR are associated with biased processing of dysphoric emotion cues among adults with MDD. Further, we will also examine whether short 5-HTTLPR allele carriers with no current or past psychopathology also display similar processing biases of dysphoric emotion cues when induced into a transient dysphoric mood. Secondary aims will examine 5-HTTLPR genotype effects for other emotion cue processing biases, such as over-identifying sadness in emotionally ambiguous stimuli, difficulty disengaging attention from dysphoric information, and self-reported tendencies to ruminate about emotional information. Our final aim is to investigate two other genetic polymorphisms (i.e., Catechol-O-methyltransferase [COMT] and tryptophan hydroxylase 2 [TPH2]) that have been associated with increased risk for MDD, impact the function of the corticolimbic emotion circuits, and have a relatively high minor allele frequency. This translational study should thus help to elucidate the mechanisms by which three common genetic polymorphisms contribute to the expression of a critical phenotype in MDD. Thus, the proposed study should advance our knowledge of the etiological and maintenance processes for MDD and provide specific direction for the design of treatment programs for this serious psychiatric problem.

描述(申请人提供)：严重抑郁障碍(MOD)是美国成年人面临的最普遍的精神问题之一。尽管MOD似乎具有很高的遗传性，但对这种疾病的遗传关联研究一直是多变和模棱两可的。识别中间表型对于促进我们对MDD的理解可能是至关重要的。神经生物学模型表明，5-羟色胺转运体(5-HTTLPR)的遗传变体在调节情绪暗示处理的广泛分布和相互关联的皮质和皮质下通路系统中发挥着至关重要的作用。一些研究人员推测，5-羟色胺能多态通过改变情绪刺激的处理，增加了情感障碍的风险和维持。我们的主要目的是使用最先进的眼球跟踪范式来检验5-HTTLPR的多态是否与成年MDD患者对烦躁情绪线索的偏向加工有关。此外，我们还将检查短的5-HTTLPR等位基因携带者在被诱导进入短暂的烦躁情绪时，是否也表现出类似的焦躁情绪线索的加工偏向。次级目标将研究5-HTTLPR基因对其他情绪线索加工偏差的影响，例如在情绪模糊的刺激中过度识别悲伤，难以将注意力从烦躁的信息中分离出来，以及自我报告的反思情绪信息的倾向。我们的最终目标是研究另外两个基因多态(即儿茶酚-O-甲基转移酶[COMT]和色氨酸羟化酶2[TPH2])，它们与MDD的风险增加相关，影响皮质边缘情绪回路的功能，并且具有相对较高的次要等位基因频率。因此，这项翻译研究应该有助于阐明三种常见的基因多态对MDD关键表型表达的影响机制。因此，拟议的研究应该促进我们对MDD的病因和维持过程的了解，并为这一严重精神问题的治疗方案的设计提供具体的指导。