Emotion-dependent functional connectivity of the default mode network in adolescent depression
Open accessAbstract
Background Functional magnetic resonance imaging research suggests that major depressive disorder (MDD) in both adults and adolescents is marked by aberrant connectivity of the default mode network (DMN) during resting state. However, emotional dysregulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in individuals with depression with short disease histories could provide insight into the etiology of MDD.Methods We collected functional magnetic resonance imaging data during an emotion identification task and during resting state from 26 medication-free adolescents (13-17 years old) with MDD and 37 well-matched healthy control subjects. We examined between-group differences in blood oxygenation level-dependent task responses and emotion-dependent and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset.Results Relative to healthy control subjects, unmedicated adolescents with MDD demonstrated reduced medial prefrontal cortex and PCC emotion-related deactivation and greater medial prefrontal cortex and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. The PCC-subcallosal cingulate connectivity remained inflexibly elevated in the subjects with MDD versus healthy control subjects during resting state. Stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset.Conclusions Adolescent depression is associated with inflexibly elevated DMN connections. Given more recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely affects normal development of functional brain networks.
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The default mode network (DMN) has been found to be significantly altered in fMRI studies of depressed adolescents.
“The second target in TARA is practicing the ability to shift neural activation away from the DMN, which has been found to be significantly altered in fMRI studies of depressed adolescents (34).”
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- Authors
- Ho, T. C., Connolly, C. G., Henje Blom, E., LeWinn, K. Z., Strigo, I. A., Paulus, M. P., Frank, G., Max, J. E., Wu, J., Chan, M., Tapert, S. F., Simmons, A. N., & Yang, T. T.
- Affiliations
- University of California, San Francisco (US)
- University of California San Diego (US)
- VA San Diego Healthcare System (US)
- University of Colorado Denver (US)
- University of Washington (US)
- Corresponding author
- Ho, Tiffany C.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 78
- Issue
- 9
- Pages
- 635-646
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4362932
- OpenAlex
- W1970348155
- Cited by
- 227
- References
- 128
- Citations by year
- 2026: 20 · 2025: 28 · 2024: 30 · 2023: 17 · 2022: 18 · 2021: 29 · 2020: 12 · 2019: 22 · 2018: 15 · 2017: 13 · 2016: 13 · 2015: 9 · 2013: 1
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH085734, R01MH085734-02S1, R01MH085734-05S1, K01MH097978)
- Swedish Research Council (350-2012-303 to EHB)
- Swedish Society of Medicine (SLS-244671 to EHB)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- adolescent depression, major depressive disorder, default mode network, functional connectivity, resting-state functional connectivity, medial prefrontal cortex, posterior cingulate cortex, subcallosal cingulate, precuneus, emotional dysregulation, depression severity
- MeSH terms
- Facial Recognition, Adolescent, Psychology, Adolescent, Brain, Brain Mapping, Major Depressive Disorder, Emotions, Female, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Neuropsychological Tests, Oxygen, Photic Stimulation, Psychoacoustics, Rest, Severity of Illness Index
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