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Aberrant intrinsic hippocampal and orbitofrontal connectivity in drug-naive adolescent patients with major depressive disorder

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Abstract

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study is supported by grants from the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Grant No. ZYJC21041), the Clinical and Translational Research Fund of Chinese Academy of Medical Sciences (Grant No. 2021-I2M-C&T-B-097), and the Natural Science Foundation of Sichuan Province (Grant No. 2022NSFSC0052).

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  1. Zilin Zhou and Yingxue Gao contributed equally to this work.

Authors and Affiliations

  1. Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, Department of Radiology, West China Hospital of Sichuan University, Chengdu, China

    Zilin Zhou, Yingxue Gao, Ruohan Feng, Weijie Bao, Kaili Liang, Hui Qiu, Lingxiao Cao, Mengyue Tang, Hailong Li, Lianqing Zhang & Xiaoqi Huang

  2. Psychoradiology Research Unit, Chinese Academy of Medical Science, West China Hospital of Sichuan University, Chengdu, China

    Xiaoqi Huang

  3. Department of Radiology, Sichuan Mental Health Center, The Third Hospital of Mianyang, Mianyang, China

    Ruohan Feng & Lihua Zhuo

  4. Department of Psychiatry, Sichuan Mental Health Center, The Third Hospital of Mianyang, Mianyang, China

    Guoping Huang

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  1. Zilin Zhou
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Contributions

ZZ and YG conceived and designed the study. XH and GH supervised the conduct of the study. RF and LZ are responsible for data acquisition. ZZ, WB, and YG analyzed the neuroimaging and clinical data. KL and LC performed the statistical analysis. ZZ, HQ and MT assisted with related literature search. ZZ and YG drafted the initial manuscript, and HL, LZ XH and GH reviewed and revised the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Xiaoqi Huang.

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This research was approved by the Ethics Committee of the Third People's Hospital of Mianyang, and it is all done in accordance with the ethical standards set out in the 1964 Declaration of Helsinki and its subsequent amendments.

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Zhou, Z., Gao, Y., Feng, R. et al. Aberrant intrinsic hippocampal and orbitofrontal connectivity in drug-naive adolescent patients with major depressive disorder. Eur Child Adolesc Psychiatry 32, 2363–2374 (2023). https://doi.org/10.1007/s00787-022-02086-4

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