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

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：重度抑郁症（MOD）是美国成年人面临的最普遍的精神病问题之一。尽管MOD似乎是高度遗传的，但该疾病的遗传关联研究是可变和模棱两可的。识别中间表型对于促进我们对MDD的理解至关重要。神经生物学模型表明，羟色胺转运蛋白（5-HTTLPR）的遗传变异在调节情绪线索处理的皮质和皮质下途径的广泛分布和相互联系的系统中起着至关重要的作用。一些研究人员推测，血清素能多态性通过改变情绪刺激的处理来增加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动范例来检查5-HTTLPR的多态性是否与MDD成年人的烦躁情绪提示的偏见处理有关。此外，我们还将检查短的5-HTTLPR等位基因携带者是否没有当前或过去的心理病理学也表现出类似的处理烦躁情绪提示的偏见，因为诱发了短暂的烦躁情绪。次要目的将检查5-HTTLPR基因型对其他情绪提示处理偏见的影响，例如过度识别情绪模棱两可的刺激的悲伤，难以将注意力从烦躁不安的信息中解散，以及自我报告的倾向以激发情绪信息。我们的最终目的是调查其他两种遗传多态性（即Catechol-O-甲基转移酶[COMT]和色氨酸羟基羟化酶2 [TPH2]），它们与MDD的增加有关，影响了Corticolimimbic Empotion Coussuits的功能，并且具有相对较高的小副层频率。因此，这项翻译研究应有助于阐明三种常见的遗传多态性有助于MDD中关键表型表达的机制。因此，拟议的研究应提高我们对MDD的病因和维护过程的了解，并为这个严重的精神病问题设计治疗计划的特定方向。