Abstract
Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.
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Acknowledgements
This study was supported by NSF Integrative Graduate Education and Research Traineeship (IGERT) Recipient Award 0801700 to MDS; NSF Graduate Research Fellowship Program (GRFP) DGE-1147470 to MDS; NIMH Neuroscience Research Training Award T32 MH020016 to MDS; NIMH 7R01MH085734, 3R01MH085734-02S1 and R01MH085734-05S1 to TTY; by the Brain and Behavior Research Foundation (formerly NARSAD) to TTY; by the American Foundation for Suicide Prevention PDF-1-064-13 to TCH; by the Swedish Research Council 350-2012-303 to EHB; by the Center of Excellence in Stress and Mental Health; and by a Veteran’s Affairs Merit Grant to ANS. We are grateful to Nisreen Mobayed, Jing Wu, Mary Luna, and Audrey Fortezzo for help with data collection and data management.
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Sacchet, M., Ho, T., Connolly, C. et al. Large-Scale Hypoconnectivity Between Resting-State Functional Networks in Unmedicated Adolescent Major Depressive Disorder. Neuropsychopharmacol 41, 2951–2960 (2016). https://doi.org/10.1038/npp.2016.76
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DOI: https://doi.org/10.1038/npp.2016.76
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