Genetics of Depression

Abstract

Categorical major depressive disorder has been the focus of most genetic studies, although some studies use continuous measures or consider both depression and anxiety. Lifetime risk of major depression is high (12-20%), heritability is below 40%, and the relative risk to first-degree relatives is approximately 3. These characteristics are challenging for current genetic methods. There have been several significant linkage findings which do not consistently replicate. Genomewide association studies have not produced significant findings, but analyses that cut across diagnostic boundaries seem promising. Candidate gene studies have been fraught with methodological problems, although the largest meta-analysis to date supported the hypothesis that 5-HTTLPR genotype and specific stressors interact to predict depressive episodes (but not lifetime risk of depression). Future steps include application of sequencing and stem cell technologies. Methods are need to build larger samples with more detailed clinical assessment. Outstanding genetic epidemiological issues should be addressed by new studies.