The heritability of MDD has been estimated at approximately 40% in population-based twin studies4, and higher in clinical samples5 or with repeated assessments.6 There is an approximately three-fold increase in risk to first-degree relatives.4 Risk is also increased by severe childhood trauma or parental loss7, probably interacting with genetic vulnerability.8 Recurrent episodes and early onset in probands predict greater familial risk, although the size of these effects is controversial.4, 9–11 Women are at two-fold greater risk of MDD, and there are probably both common and independent genetic factors in men and women, with similar heritability.12, 13 Although MDD is more frequent in relatives of probands with bipolar disorders and schizophrenia, those disorders are not more frequent in relatives of MDD probands.14 The degree or nature of overlap in genetic factors underlying these disorders remains unclear.
