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  Inflexible functional connectivity of the dorsal anterior cingulate cortex in adolescent major depressive disorder

Ho, T. C., Sacchet, M. D., Connolly, C. G., Margulies, D. S., Tymofiyeva, O., Paulus, M. P., et al. (2017). Inflexible functional connectivity of the dorsal anterior cingulate cortex in adolescent major depressive disorder. Neuropsychopharmacology, 42(12), 2434-2445. doi:10.1038/npp.2017.103.

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 Creators:
Ho, Tiffany C.1, 2, Author
Sacchet, Matthew D.2, 3, Author
Connolly, Colm G.1, Author
Margulies, Daniel S.4, Author              
Tymofiyeva, Olga5, Author
Paulus, Martin P.6, 7, Author
Simmons, Alan N.7, 8, Author
Gotlib, Ian H.2, 9, Author
Yang, Tony T.1, Author
Affiliations:
1Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of California, San Francisco, CA, USA, ou_persistent22              
2Department of Psychology, Stanford University, CA, USA, ou_persistent22              
3Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA, USA, ou_persistent22              
4Max Planck Research Group Neuroanatomy and Connectivity, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_1356546              
5Department of Radiology, University of California, San Francisco, CA, USA, ou_persistent22              
6Laureate Institute for Brain Research, Tulsa, OK, USA, ou_persistent22              
7Department of Psychiatry, University of California, San Francisco, CA, USA, ou_persistent22              
8Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, University of California San Diego, CA, USA, ou_persistent22              
9Neurosciences Program, Stanford University, CA, USA, ou_persistent22              

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 Abstract: Recent evidence suggests that anterior cingulate cortex (ACC) maturation during adolescence contributes to or underlies the development of major depressive disorder (MDD) during this sensitive period. The ACC is a structure that sits at the intersection of several task-positive networks (eg, central executive network, CEN), which are still developing during adolescence. While recent work using seed-based approaches indicate that depressed adolescents show limited task-evoked vs resting-state connectivity (termed ‘inflexibility’) between the ACC and task-negative networks, no study has used network-based approaches to investigate inflexibility of the ACC in task-positive networks to understand adolescent MDD. Here, we used graph theory to compare flexibility of network-level topology in eight subregions of the ACC (spanning three task-positive networks) in 42 unmedicated adolescents with MDD and 53 well-matched healthy controls. All participants underwent fMRI scanning during resting state and a response inhibition task that robustly engages task-positive networks. Relative to controls, depressed adolescents were characterized by inflexibility in local efficiency of a key ACC node in the CEN: right dorsal anterior cingulate cortex/medial frontal gyrus (R dACC/MFG). Furthermore, individual differences in flexibility of local efficiency of R dACC/MFG significantly predicted inhibition performance, consistent with current literature demonstrating that flexible network organization affords successful cognitive control. Finally, reduced local efficiency of dACC/MFG during the task was significantly associated with an earlier age of depression onset, consistent with prior work suggesting that MDD may alter functional network development. Our results support a neurodevelopmental hypothesis of MDD wherein dysfunctional self-regulation is potentially reflected by altered ACC maturation.

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Language(s): eng - English
 Dates: 2017-04-152016-11-292017-05-142017-07-192017-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/npp.2017.103
PMID: 28553837
PMC: PMC5645733
Other: Epub 2017
 Degree: -

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Grant ID : PDF-1-064-13
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Funding organization : American Foundation for Suicide Prevention
Project name : -
Grant ID : 080700
Funding program : IGERT Award
Funding organization : National Science Foundation (NSF)
Project name : -
Grant ID : DGE-1147470
Funding program : Graduate Research Fellowship Award
Funding organization : National Science Foundation (NSF)
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Grant ID : R01MH085734 ; R01MH101495 ; R01HD072074 ; R21AT009173
Funding program : -
Funding organization : National Institutes of Health (NIH)
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Funding organization : UCSF Research Evaluation and Allocation Committee
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Funding program : -
Funding organization : Jacobs Foundation
Project name : -
Grant ID : I-1-CX000715
Funding program : -
Funding organization : Center of Excellence in Stress and Mental Health and Veteran’s Affairs
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Grant ID : -
Funding program : Young Investigator Award
Funding organization : Brain and Behavior Research Foundation

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Title: Neuropsychopharmacology
Source Genre: Journal
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Publ. Info: New York, NY : No longer published by Elsevier
Pages: - Volume / Issue: 42 (12) Sequence Number: - Start / End Page: 2434 - 2445 Identifier: ISSN: 0893-133X
CoNE: https://pure.mpg.de/cone/journals/resource/954925558485