Default Mode and Frontoparietal Network Dynamics: Associations with Familial Risk for Depression and Stress Sensitivity

Background: Major Depressive Disorder (MDD) is associated with alterations within the default mode (DMN) and frontoparietal (FPN) networks. However, it is unclear whether changes in these networks occur prior to onset in youth at high familial risk for MDD or are a consequence of MDD. Moreover, studies examining premorbid MDD vulnerability markers have focused on static rather than dynamic network properties, which could further elucidate DMN-FPN imbalances linked to MDD risk.

Methods: Eighty-nine unaffected 12-14-year-old adolescents both with ( = 27) and without ( = 62) a maternal history of MDD completed a resting state functional magnetic resonance imaging scan and self-report assessments of depressive symptoms and perceived stress at baseline and every three months across a two-year span. A coactivation pattern (CAP) analysis was conducted to examine functional network dynamic properties, including time spent in each CAP (total number of volumes), CAP persistence (number of consecutive volumes in each CAP), and number of transitions between posterior DMN-FPN and canonical DMN CAPs. Multilevel models estimated whether DMN-FPN dynamic properties predicted future depressive symptoms and stress sensitivity.

Results: High-risk adolescents spent more time and exhibited a longer persistence in a posterior DMN-FPN CAP. DMN-FPN CAP persistence predicted future perceived stress, but only among high-risk adolescents. High-risk adolescents characterized by high DMN-FPN persistence reported greater future perceived stress, whereas those showing low DMN-FPN persistence had reduced perceived stress over time. Unexpectedly, DMN-FPN dynamics did not predict future depressive symptoms.

Conclusions: Altered DMN-FPN CAP properties among high-risk adolescents mirror alterations among individuals with MDD, suggesting that DMN-FPN dynamics may be a risk marker rather than consequence of MDD. Furthermore, longer DMN-FPN CAP persistence increases vulnerability in high-risk adolescents by predicting greater future stress sensitivity, a well-known catalyst for MDD. Replication in a larger sample is warranted.