Reduced network connectivity in healthy children with maternal history of depression in the ABCD cohort

Major Depressive Disorder (MDD) is a leading cause of disability worldwide and affects up to twenty percent of children and adolescents. Having a mother with Major Depressive Disorder is one of the strongest predictors of depression in late adolescence and early adulthood. Neuroimaging studies consistently report MDD associated dysfunction within the frontal-parietal cognitive control network, default mode network, and salience network. However, it is unclear whether alterations in these networks are due to current symptomatology or are evident prior to symptom onset. We leverage maternal history of depression (MHD) as a model for assessing neural contributions to MDD risk. To investigate this, we used the network based statistic, a graph theory based approach to explore differences in resting state network connectivity among 2,185 healthy adolescents, ages 9-10 yrs in the ABCD study (abcdstudy.org) with and without a maternal history of depression. Results show reduced network connectivity in healthy children with MHD, which was primarily driven by reduced connectivity in female children with MHD. Further we identify sex specific differences in the frontal-parietal cognitive control network, default mode network, and salience network and sex by MHD interaction effects in these neural networks. This work reaffirms the neural mechanisms underlying depression vulnerability, an effort that, ultimately, may facilitate interventions aimed at preventing the consequences of adolescent depression in this high-risk population.