Current perspectives on the genetics of unipolar depression

Evidence regarding the heritability of unipolar depression is evaluated. The data reviewed here support the involvement of genetic factors in the etiology of unipolar depression and its suitability for independent genetic inquiry, despite our inability to identify the mode(s) of transmission or identify a candidate locus. Continued progress in testing etiologic hypotheses requires (a) clarification of the mode of transmission; (b) resolution of phenotypic and potential genotypic heterogeneity; (c) general agreement on a "gold standard" for assessment of the unipolar phenotype; (d) the continued application of available quantitative methods to take into account the effects of ascertainment bias, sex effects, cohort effects, and variable/late age at onset; and (e) incorporation of quantitative indicators correlated with liability in multivariate analysis to improve the stability/validity of phenotypic determinations in segregation and linkage analysis. We present several recommendations regarding the extension of current methodologies in human population and quantitative genetics to help resolve these issues.