The Genomic Approaches to Major Depression

Major depression is a chronic state of depressed mood with significant genetic predisposition. Although a lot of efforts has been tried to localize or associate the genes of major depression, etiological heterogeneity and complexity of this disorder has greatly hold back the use of traditional linkage strategies and candidate gene approaches. Recent advances in high throughput genotyping and microarray techniques have proffered opportunities for comprehensive investigation on genetic alterations and expressions on a scale not previously possible. It has become feasible to find genes with small effect size in major depression using genome-wide association scanning and to identify new pathways or mechanisms of psychopharmacology by the application of functional genomics. In the era of genomic approach to the pathophysiology of major depression, the authors suggest (1) reducing the heterogeneity of major depression by subgrouping the patients according to biological traits such as responses to antidepressant treatments, (2) searching for genes with small effect size using association scanning strategy, genomic control and DNA pooling techniques in genotyping, and (3) developing animal models with genetic vulnerability to major depression by ethylnitrosourea (ENU) mutagenesis technology and efficient behavioral screening tests.