Are genetic risk factors for current depressive symptoms good proxies for genetic risk factors for syndromal major depression (MD)?

In over 9000 twins from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, the occurrence of all nine DSM symptomatic criteria for MD in the last year was assessed at personal interview and then grouped by their temporal co-occurrence. The DSM criteria which occurred outside (OUT) v. inside of (IN) MD episodes were then separated. We calculated tetrachoric correlations for OUT and IN depressive criteria in monozygotic (MZ) and dizygotic (DZ) pairs and fitted univariate and bivariate ACE twin models using OpenMx.

The mean twin correlations (±95% CIs) for IN depressive criteria were substantially higher than for OUT depressive criteria in both MZ [+0.35 (0.32–0.38) v. 0.20 (0.17–0.24)] and DZ pairs [0.20 (0.17–0.24) v. 0.10 (0.04–0.16]. The mean IN–OUT cross-correlation in MZ and DZ pairs was modest [+0.15 (0.07–0.24) and +0.07 (0.03–0.12)]. The mean heritability estimates for the nine In v. Out depressive criteria was 0.31 (0.22–0.41) and 0.15 (0.08–0.21), in MZ and DZ pairs, respectively. The mean genetic correlation between the nine IN and OUT depressive criteria was +0.07 (−0.07 to 0.21).

Depressive criteria occurring outside depressive episodes are less heritable than those occurring within. These two ways criteria can manifest are not closely genetically related. Current depressive symptoms – most of which are occurring outside of depressive episodes – are not, for genetic studies, good proxies for MD.