Dynamic Functional Connectivity, Major Depression, and Suicidal Ideation in Children

Abstract

There is an urgent need to advance understanding of the neural underpinnings of depression, especially early in the life span. Examination of neural dynamics using resting-state functional magnetic resonance imaging (fMRI) data can provide indices of neural flexibility, which may provide important new insights for the neurobiology of pediatric depression. Here we applied Hidden Markov Modeling (HMM) to resting-state fMRI data to investigate neural flexibility in relation to depression and suicidal thinking in children. We utilized data from the Adolescent Brain Cognitive Development℠ Study (ABCD Study), and included data from 10,763 children (9-10 years) who completed two 5-min resting state fMRI scans at the baseline visit. After applying the NeuroMark framework to the data, HMM was applied with a varying number of states; a six-state model was selected from candidate models based on between-scan reliability. We applied linear mixed-effect modeling to test the relationship between two clinical predictors: current major depressive disorder (MDD) diagnosis and presence of suicidal ideation (SI) with our primary outcome for neural flexibility: the frequency of transitions between HMM-derived states ("state-switching"), while including sex, age, and other socio-demographic variables as covariates. Analyses were conducted both with and without correction for head motion. We also explored relationships with total time and dwell time in each state of the six states. Lower state-switching during rest was associated with both MDD and SI, although these findings were no longer significant after correcting for head motion. Notably, state-switching was inversely related to head motion and was higher in females than males. Exploratory analysis showed that MDD was associated with shorter dwell time in one state and longer dwell time in another, suggesting altered temporal persistence of specific neural configurations. Tentative evidence supported our hypothesis that lower state-switching in children with MDD and SI may reflect a reduction in brain flexibility, potentially contributing to a tendency to become "stuck" in negative patterns of thinking and feeling. However, the relatively low frequency of these problems in late childhood reduced statistical power after correcting for motion. Future research is needed to assess these relationships at later adolescent time points, when higher prevalence of depression and SI and lower prevalence of head motion will allow more powerful tests of these associations.

Keywords: depression; dynamic functional network connectivity; fMRI; hidden Markov model; resting state; suicidal ideation.