ABSTRACT
Major depressive disorder (MDD) is a common and often disabling disorder, with an estimated lifetime prevalence of 17% [1]. In 1999, unipolar depression ranked fifth among the leading causes of disease burden worldwide [2]. Given its high prevalence and associated morbidity, efforts to improve our understanding and treatment of depression have urgent public health significance. Over the past two decades, the genetic basis of depression has been studied with increasingly sophisticated epidemiological and molecular genetic methods. Despite variation in the populations studied and methods of assessment, family and twin studies have provided compelling evidence that major depression is familial and that genes account for a substantial proportion of this familiality. Molecular genetic studies of depression are now appearing with increasing frequency and offer the promise of identifying specific susceptibility genes. In the sections that follow, we will review this work, highlighting both established findings and unresolved questions about the genetic basis of
depression. In particular, we will see that the heterogeneity and complexity of the phenotype of depression represent significant challenges to the progress of molecular genetic studies. To date, no specific susceptibility genes have been established, but with advances in phenotypic characterization, molecular genetic technologies, and statistical methods, the prospect of identifying such genes has become a foreseeable goal.
