Association of Intrinsic Brain Architecture With Changes in Attentional and Mood Symptoms During Development

Question  Can brain imaging predict future psychiatric symptoms in children?

Findings  In this 4-year longitudinal cohort study, distinct patterns of resting-state functional connectivity in healthy children predicted changes in psychiatric symptoms. Weaker positive dorsolateral prefrontal connectivity with medial prefrontal cortex predicted a better developmental trajectory for attentional symptoms, whereas weaker positive dorsolateral prefrontal connectivity with subgenual anterior cingulate cortex predicted a worse trajectory for internalizing symptoms (eg, anxiety/depression).

Meaning  Brain imaging measures can contribute to early identification of children at risk for common psychiatric disorders and thus identify children in need of preventive treatments.

Importance  Understanding the neurodevelopmental trajectory of psychiatric symptoms is important for improving early identification, intervention, and prevention of mental disorders.

Objective  To test whether the strength of the coupling of activation between specific brain regions, as measured by resting-state functional magnetic resonance imaging (fMRI), predicted individual children’s developmental trajectories in terms of attentional problems characteristic of attention-deficit/hyperactivity disorder and internalizing problems characteristics of major depressive disorder (MDD).

Design, Setting, and Participants  A community cohort of 94 children was recruited from Vanderbilt University between 2010 and 2013. They were followed up longitudinally for 4 years and the data were analyzed from 2016 to 2019. Based on preregistered hypotheses and an analytic plan, we examined whether specific brain connectivity patterns would be associated with longitudinal changes in scores on the Child Behavior Checklist (CBCL), a parental-report assessment used to screen for emotional, behavioral, and social problems and to predict psychiatric illnesses.^1,2

Main Outcomes and Measures  We used the strength of resting-state fMRI connectivity at age 7 years to predict subsequent changes in CBCL measures 4 years later and investigated the mechanisms of change by associating brain connectivity changes with changes in the CBCL.

Results  We analyzed data from a longitudinal brain development study involving children assessed at age 7 years (n = 94; 41 girls [43.6%]) and 11 years (n = 54; 32 girls [59.3%]). As predicted, less positive coupling at age 7 years between the medial prefrontal cortex and dorsolateral prefrontal cortex (DLPFC) was associated with a decrease in attentional symptoms by age 11 years (t₄₉ = 2.38; P = .01; β = 0.32). By contrast, a less positive coupling between a region implicated in mood, the subgenual anterior cingulate cortex (sgACC), and DLPFC at age 7 years was associated with an increase in internalizing (eg, anxiety/depression) behaviors by age 11 years (t₄₉ = −2.4; P = .01; β = −0.30). Logistic regression analyses revealed that sgACC-DLPFC connectivity was a more accurate predictor than baseline CBCL measures for progression to a subclinical score on internalization (t₅₀ = −2.61; P = .01; β = −0.29). We then replicated and extended the sgACC-DLPFC result in an independent sample of children with (n = 25) or without (n = 18) familial risk for MDD.

Conclusions and Relevance  These resting-state fMRI metrics are promising biomarkers for the early identification of children at risk of developing MDD or attention-deficit/hyperactivity disorder.