Contributions from resting state functional connectivity and familial risk to early adolescent-onset MDD: Results from the Adolescent Brain Cognitive Development study

Background: Family history of Major Depressive Disorder (MDD) is a robust predictor of MDD onset, especially in early adolescence. We examined the relationships between familial risk for depression and alterations to resting state functional connectivity (rsFC) within the default mode network (wDMN) and between the DMN and the left/right hippocampus (DMN-LHIPP/DMN-RHIPP) to the risk for early adolescent MDD onset. Methods: We examined 9403 youth aged nine to eleven from the Adolescent Brain Cognitive Development study. Depressive symptoms were measured with the parent-reported Child Behavior Checklist. Both youth and their parents completed the Kiddie Schedule for Affective Disorders and Schizophrenia, which provided MDD diagnoses. A family history screen was administered to determine familial risk for depression. Youth underwent a resting state functional magnetic resonance imaging scan, providing us with rsFC data. Results: Negative wDMN rsFC was associated with child-reported current depression, both child-and parent reported past depression, and parent-reported current depressive symptoms. No difference was found in wDMN, DMN-LHIPP or DMN-RHIPP rsFC in children with or without familial risk for depression. Familial risk for depression interacted with wDMN rsFC in association with child-reported past MDD diagnosis and parent reported current depressive symptoms. Limitations: Information such as length of depressive episodes and age of onset of depression was not collected. Conclusions: Altered wDMN rsFC in youth at familial risk for depression may be associated with increased risk for MDD onset in adolescence, but longitudinal studies are needed to test this hypothesis.

Automated summary

Family history of Major Depressive Disorder (MDD) is a strong predictor of MDD onset in early adolescence. Negative wDMN rsFC is associated with current depression in children and current depressive symptoms in parents. Familial risk for depression interacts with wDMN rsFC in association with past MDD diagnosis in children and current depressive symptoms in parents.