One implication is for future genetic studies. In a first phase, it should be possible to elucidate the bulk of the common variant genetic architecture of MDD using a cost-effective shortcut – large studies of genotyped individuals who complete online self-report assessments of lifetime MDD (a sample size approaching 1 million MDD cases may be achievable by 2020). Use of online assessment could allow for recording of a broad range of phenotypes including comorbidities and putative environmental exposures, but the key feature being large samples with consistently assessed measures. In a second phase, with a relatively complete understanding of the genetic basis of major depression, one could then evaluate smaller samples of carefully phenotyped individuals with MDD to understand the clinical importance of the genetic results. Subsequent empirical studies may show that it is possible to stratify MDD cases at first presentation to identify individuals at high risk for recurrence, poor outcome, poor treatment response, or who might subsequently develop a psychiatric disorder requiring alternative pharmacotherapy (e.g., schizophrenia or bipolar disorder). This could form a cornerstone of precision medicine in psychiatry.
