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Clinical depression commonly emerges in adolescence, which is also a time of developing cognitive ability and related large-scale functional brain networks implicated in depression. In depressed adults, abnormalities in the dynamic functioning of frontoinsular networks, in particular, have been observed and linked to negative rumination. Thus, network dynamics may provide new insight into teen pathophysiology. Here, adolescents (n = 45, ages 13-19) with varying severity of depressive symptoms completed a resting-state functional MRI scan. Functional networks were evaluated using co-activation pattern analysis to identify whole-brain states of spatial co-activation that recurred across participants and time. Measures included: dwell time (proportion of scan spent in that network state), persistence (volume-to-volume maintenance of a network state), and transitions (frequency of moving from state A to state B). Analyses tested associations between depression or trait rumination and dynamics of network states involving frontoinsular and default network systems. Results indicated that adolescents showing increased dwell time in, and persistence of, a frontoinsular-default network state involving insula, dorsolateral and medial prefrontal cortex, and posterior regions of default network, reported more severe symptoms of depression. Further, adolescents who transitioned more frequently between the frontoinsular-default state and a prototypical default network state reported higher depression. Increased dominance and transition frequency of frontoinsular-default network states were also associated with higher rumination, and rumination mediated the associations between network dynamics and depression. Findings support a model in which abnormal frontoinsular dynamics confer vulnerability to maladaptive introspection, which in turn contributes to symptoms of adolescent depression.

Background: Adolescence is a developmental period in which depression and related mood syndromes often emerge, but few objective markers exist to guide diagnosis or predict symptoms. One potential mood marker is the functioning of frontoinsular networks, which undergo substantial development in adolescence and have been implicated in adult depression. To test this hypothesis, we used task-based neuroimaging to evaluate whether frontoinsular network dysfunction was linked to current and prospective mood health in adolescents., Methods: Adolescents (n = 40, 13-19 years of age) reporting varying levels of depressive symptom severity performed an emotional working memory task with neuroimaging. Next, teens completed a 2-week follow-up consisting of a daily diary report of negative affect and final report of depressive symptoms (n = 28 adherent). Analyses tested associations between task-related functional connectivity in frontoinsular networks and baseline or prospective measures of mood health over 2-week follow-up., Results: Frontoinsular task response was associated with higher current depression severity (p = .049, η p 2  = .12), increases in future depression severity (p = .018, η p 2  = .23), and more intense and labile negative affect in daily life (ps = .015 to .040, η p 2  = .22 to .30). In particular, hypoconnectivity between insula and lateral prefrontal regions of the frontoparietal network was related to both baseline and prospective mood health, and hyperconnectivity between insula and midline or temporal regions of the default network was related to prospective mood health., Conclusions: These findings indicate that frontoinsular imbalances are related to both current depression and changes in mood health in the near future and suggest that frontoinsular markers may hold promise as translational tools for risk prediction., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)