Genetic Associations with Biased Processing of Emotion Cues in MDD

描述（由申请人提供）：严重抑郁症（MOD）是美国成年人面临的最普遍的精神问题之一。虽然MOD似乎是高度遗传的，这种疾病的遗传关联研究一直是可变的和模棱两可的。识别中间表型可能对我们进一步理解MDD至关重要。神经生物学模型表明，5-羟色胺转运体（5-HTTLPR）的遗传变异在调节情绪线索处理的皮层和皮层下通路的广泛分布和相互连接的系统中起着至关重要的作用。一些研究人员推测，多巴胺能多态性通过改变对情绪刺激的处理，增加了情感障碍的风险和维持。我们的主要目的是使用一个国家的最先进的眼动跟踪范例，以检查是否多态性的5-HTTLPR与抑郁症的成年人之间的烦躁情绪线索的偏见处理。此外，我们还将研究是否短5-HTTLPR等位基因携带者没有当前或过去的精神病理学也显示出类似的处理偏见的烦躁情绪线索时，诱导到一个短暂的烦躁情绪。次要目标将检查5-HTTLPR基因型对其他情绪线索处理偏差的影响，例如在情绪模糊的刺激中过度识别悲伤，难以从焦虑信息中分离注意力，以及自我报告的对情绪信息进行反刍的倾向。我们的最终目标是研究另外两种遗传多态性（即，儿茶酚-O-甲基转移酶[COMT]和色氨酸羟化酶2 [TPH 2]）与MDD风险增加相关，影响皮质边缘情感回路的功能，并具有相对较高的次要等位基因频率。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关键表型表达的机制。因此，拟议中的研究应该推进我们的知识的病因和维护过程中的MDD，并提供具体的方向设计的治疗方案，这一严重的精神问题。

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.