Altered patterns of central executive, default mode and salience network activity and connectivity are associated with current and future depression risk in two independent young adult samples

Neural markers of pathophysiological processes underlying the dimension of subsyndromal-syndromal-level depression severity can provide objective, biologically informed targets for novel interventions to help prevent the onset of depressive and other affective disorders in individuals with subsyndromal symptoms, and prevent worsening symptom severity in those with these disorders. Greater functional connectivity (FC) among the central executive network (CEN), supporting emotional regulation (ER) subcomponent processes such as working memory (WM), the default mode network (DMN), supporting self-related information processing, and the salience network (SN), is thought to interfere with cognitive functioning and predispose to depressive disorders. We examined in young adults (1) relationships among activity and FC in these networks and current depression severity, using a paradigm designed to examine WM and ER capacity in n = 90, age = 21.7 (2.0); (2) the extent to which these relationships were specific to depression versus mania/hypomania; (3) whether findings in a first, "discovery" sample could be replicated in a second, independent, "test" sample of young adults n = 96, age = 21.6 (2.1); and (4) whether such relationships also predicted depression at up to 12 months post scan and/or mania/hypomania severity in (n = 61, including participants from both samples, age = 21.6 (2.1)). We also examined the extent to which there were common depression- and anxiety-related findings, given that depression and anxiety are highly comorbid. In the discovery sample, current depression severity was robustly predicted by greater activity and greater positive functional connectivity among the CEN, DMN, and SN during working memory and emotional regulation tasks (all ps < 0.05 qFDR). These findings were specific to depression, replicated in the independent sample, and predicted future depression severity. Similar neural marker-anxiety relationships were shown, with robust DMN-SN FC relationships. These data help provide objective, neural marker targets to better guide and monitor early interventions in young adults at risk for, or those with established, depressive and other affective disorders.