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Frontolimbic network topology associated with risk and presence of depression in adolescents: A study using a composite risk score in Brazil

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Leehyun Yoon, Fernanda Rohrsetzer, Lucas Battel, Mauricio Anes, Pedro H. Manfro, Luis A. Rohde, Anna Viduani, Zuzanna Zajkowska, Valeria Mondelli, Christian Kieling, Johnna R. Swartz

Original languageEnglish
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Early online date28 Mar 2022
DOIs
Accepted/In press20 Mar 2022
E-pub ahead of print28 Mar 2022

Bibliographical note

Funding Information: We are extremely grateful to the schools and individuals who participated in this study, and to all members of the IDEA team for their dedication, hard work, and insights. The IDEA project, to which this research belongs, is supported by the MQ Brighter Futures Programme (Grant No. MQBF/1 IDEA [to VM, CK, and JRS]), Medical Research Council (Grant No. MC_PC_MR/R019460/1 [to CK and VM]), and Academy of Medical Sciences (Grant No. GCRFNG∖100281 [to CK]) under the Global Challenges Research Fund. This work was also supported by research grants from the Brazilian public funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (Grant Nos. 477129/2012-9 and 445828/2014-5 [to CK and LAR]), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Grant No. 62/2014 [to CK]), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grant No. 17/2551-0001009-4 [to CK]). CK is a Conselho Nacional de Desenvolvimento Científico e Tecnológico researcher and an Academy of Medical Sciences Newton Advanced Fellow. VM is supported by the Medical Research Foundation (Grant No. MRF-160-0005-ELPMONDE) and National Institute for Health Research Mental Health Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the National Health Service, National Institute for Health Research, or Department of Health and Social Care. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. LY had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. LY, VM, CK, and JRS were responsible for study concept and design. All authors were responsible for acquisition, analysis, and interpretation of data. LY drafted the original manuscript. All authors critically revised the manuscript for important intellectual content. LY performed statistical analysis. LAR, VM, CK, and JRS obtained funding. The sociodemographic and self-reported measures were used and reported in another article (50) that detailed the protocol for the larger IDEA-RiSCo study. A subset of resting-state functional MRI data (i.e. 29 adolescents in the MDD group) was used and reported in another article (69), which was a preliminary study that examined the feasibility of MRI research in adolescents in Brazil. Task-based functional MRI data and sociodemographic and self-reported measures from this cohort of participants have been reported in another article (51). VM has received research funding from Johnson & Johnson, a pharmaceutical company interested in the development of anti-inflammatory strategies for depression, but the research described in this article is unrelated to this funding. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: We are extremely grateful to the schools and individuals who participated in this study, and to all members of the IDEA team for their dedication, hard work, and insights. The IDEA project, to which this research belongs, is supported by the MQ Brighter Futures Programme (Grant No. MQBF/1 IDEA [to VM, CK, and JRS]), Medical Research Council (Grant No. MC_PC_MR/R019460/1 [to CK and VM]), and Academy of Medical Sciences (Grant No. GCRFNG∖100281 [to CK]) under the Global Challenges Research Fund. This work was also supported by research grants from the Brazilian public funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (Grant Nos. 477129/2012-9 and 445828/2014-5 [to CK and LAR]), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Grant No. 62/2014 [to CK]), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grant No. 17/2551-0001009-4 [to CK]). CK is a Conselho Nacional de Desenvolvimento Científico e Tecnológico researcher and an Academy of Medical Sciences Newton Advanced Fellow. VM is supported by the Medical Research Foundation (Grant No. MRF-160-0005-ELPMONDE ) and National Institute for Health Research Mental Health Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the National Health Service, National Institute for Health Research, or Department of Health and Social Care. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2022 Society of Biological Psychiatry

King's Authors

Abstract

Background: There have been significant challenges in understanding functional brain connectivity associated with adolescent depression, including the need for a more comprehensive approach to defining risk, the lack of representation of participants from low- and middle-income countries, and the need for network-based approaches to model connectivity. The current study aimed to address these challenges by examining resting-state functional connectivity of frontolimbic circuitry associated with the risk and presence of depression in adolescents in Brazil. Methods: Adolescents in Brazil ages 14 to 16 years were classified into low-risk, high-risk, and depressed groups using a clinical assessment and composite risk score that integrates 11 sociodemographic risk variables. After excluding participants with excessive head movement, resting-state functional magnetic resonance imaging data of 126 adolescents were analyzed. We compared group differences in frontolimbic network connectivity using region of interest–to–region of interest, graph theory, and seed-based connectivity analyses. Associations between self-reported depressive symptoms and brain connectivity were also explored. Results: Adolescents with depression showed greater dorsal anterior cingulate cortex (ACC) connectivity with the orbitofrontal cortex compared with the 2 risk groups and greater dorsal ACC global efficiency than the low-risk group. Adolescents with depression also showed reduced local efficiency and a lower clustering coefficient of the subgenual ACC compared with the 2 risk groups. The high-risk group also showed a lower subgenual ACC clustering coefficient relative to the low-risk group. Conclusions: These findings highlight altered connectivity and topology of the ACC within frontolimbic circuitry as potential neural correlates and risk factors of developing depression in adolescents in Brazil. This study broadens our understanding of the neural connectivity associated with adolescent depression in a global context.

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