憂鬱症分子遺傳研究及研究方法的現況

Recent Molecular Genetic Studies and Methodological Issues in Major Depression Research

憂鬱症是一個遺傳性複雜的精神疾病，涉及眾多的致病或易感性的相關基因，而這些基 因的表現又受到環境因素包括壓力的影響。過去個案－－對照的基因相關研究是憂鬱症遺傳 研究的主流，最近幾年全基因組基因表現微陣列及全基因組關聯研究等開始應用在憂鬱症的 遺傳研究。個案－－對照的基因相關研究有發現幾個憂鬱症相關基因變異，但後續的研究多 無法重複驗證。因為憂鬱症的發生受到環境因素的影響，最近的遺傳研究也包括壓力變項， 幾個基因變異被重複驗證與壓力相互作用影響憂鬱症的發生。近幾年發表的幾篇全基因組關 聯研究發現的憂鬱症相關基因變異雖然沒有達到期望的顯著統計意義，但這些結果仍可提供 有趣的候選基因和基因組區域作進一步研究。目前憂鬱症遺傳研究尚無重大突破，不過隨著 遺傳學研究方法的快速增長，一些新的技術（ 如全基因組定序 ）很快將可用於大規模的研 究。這些方法提供了新的途徑，有機會找到憂鬱症的相關基因，為憂鬱症提供更好的預防和 治療方式。

Major depressive disorder (MDD) is a genetically complex mental disorder involving numerous susceptible genes whose expression may be modulated by environmental factors. In the past decade, case-control association approaches have been the mainstream in MDD genetic studies. But whole genome gene-ex- pression microarray and genome-wide association studies have begun to emerge in recent years. Genetic association studies have suggested several genes related to MDD, although the results to date are inconclusive and no single genetic variation has been identified to increase the risk of depression substantially. Recent ap- proaches based on gene-environment interaction have demonstrated more consis- tent findings. Therefore, the usefulness from the study results of case-control stud- ies is limited by present knowledge of MDD pathophysiology. Genome-wide association studies are not constrained by our limited knowledge. Although the results of several recent genome-wide association studies did not reach the desired level of statistical significance, these studies do support interesting candidate genes and genomic regions for further study. In short, the field of genetic studies in gen- eral has been disappointing because to find common gene variants of large effect in MDD pathogenesis has been unsuccessful. However, the field of psychiatric genetics is rapidly growing, and several new technological advances (e.g.whole- genome sequencing) will be soon available for large-scale studies. These ap- proaches provide exciting new avenues to identify new candidate genes for MDD. A better understanding of the MDD-related genes may potentially lead to develop- ing effective prevention and treatment of this disease.