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Lateralization of the sgACC‐Based Neural Network in Treatment‐Resistant Depression.

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Title: Lateralization of the sgACC‐Based Neural Network in Treatment‐Resistant Depression.
Authors: Zhao, Xinyu (AUTHOR), Xia, Shiyu (AUTHOR), Yu, Xiaohui (AUTHOR), Kang, Yukun (AUTHOR), Long, Jiang (AUTHOR), Liu, Fang (AUTHOR), Hu, Xiao (AUTHOR), Xu, Jianqin (AUTHOR), Roberts, Neil (AUTHOR), Xing, Haoyang (AUTHOR), Cheng, Bochao (AUTHOR), Bose, Chandra (AUTHOR)
Source: Depression & Anxiety (1091-4269). 3/20/2026, Vol. 2026, p1-14. 14p.
Subjects: Functional connectivity, Mental depression, Neural circuitry, Neuromodulation, Functional magnetic resonance imaging, Lateral dominance, Cingulate cortex
Abstract: Background: While the left subgenual anterior cingulate cortex (sgACC) is a validated target for treating major depressive disorder (MDD) (e.g., with rTMS), the therapeutic relevance of the right sgACC is unknown. Given emerging evidence that treatment‐resistant depression (TRD) and non‐TRD (nTRD) may involve distinct neural circuits, a more precise, circuit‐based understanding is needed. This study, therefore, sought to determine the degree of sgACC functional lateralization and to elucidate TRD‐specific neural mechanisms, thereby informing the development of targeted neuromodulation therapies. Methods: Resting‐state fMRI (rs‐fMRI) data were acquired for 20 patients with TRD, 53 patients with nTRD, and 51 healthy controls (HCs). Analysis was performed to compare the static functional connectivity (sFC), dynamic functional connectivity (dFC), and effective connectivity via Granger causality analysis (GCA) of left and right sgACC between the three groups, followed by clinical correlation analyses. Results: Group analysis revealed significant sFC and dFC between left sgACC and temporal pole (TP), fusiform gyrus (FG), parahippocampal gyrus (PHG), and orbitofrontal cortex (OFC), and between right sgACC and cerebellum posterior lobule (CPL) and right dorsolateral prefrontal cortex (DLPFC.R). Furthermore, GCA showed increased effective connectivity between bilateral sgACC and left caudate (CAU.L), left thalamus (THA.L), right postcentral gyrus (PoCG.R), and DLPFC.L. Compared to the nTRD group the TRD group showed decreased sFC and dFC between sgACC and DLPFC and cerebellum, along with decreased effective connectivity between sgACC and CAU and DLPFC, indicating disrupted fronto‐limbic and cerebellar circuits in TRD. Conclusion: The distinct sgACC‐centered connectivity profiles of TRD and nTRD delineate a neurobiological continuum across MDD subtypes, pinpointing the sgACC, DLPFC, CAU, and cerebellum as key circuit targets for individualized neuromodulation in TRD. [ABSTRACT FROM AUTHOR]
Copyright of Depression & Anxiety (1091-4269) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Label: Title
  Group: Ti
  Data: Lateralization of the sgACC‐Based Neural Network in Treatment‐Resistant Depression.
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  Data: <searchLink fieldCode="AR" term="%22Zhao%2C+Xinyu%22">Zhao, Xinyu</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xia%2C+Shiyu%22">Xia, Shiyu</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yu%2C+Xiaohui%22">Yu, Xiaohui</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kang%2C+Yukun%22">Kang, Yukun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Long%2C+Jiang%22">Long, Jiang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Fang%22">Liu, Fang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hu%2C+Xiao%22">Hu, Xiao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xu%2C+Jianqin%22">Xu, Jianqin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Roberts%2C+Neil%22">Roberts, Neil</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xing%2C+Haoyang%22">Xing, Haoyang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cheng%2C+Bochao%22">Cheng, Bochao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bose%2C+Chandra%22">Bose, Chandra</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Depression+%26+Anxiety+%281091-4269%29%22">Depression & Anxiety (1091-4269)</searchLink>. 3/20/2026, Vol. 2026, p1-14. 14p.
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  Data: <searchLink fieldCode="DE" term="%22Functional+connectivity%22">Functional connectivity</searchLink><br /><searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Neural+circuitry%22">Neural circuitry</searchLink><br /><searchLink fieldCode="DE" term="%22Neuromodulation%22">Neuromodulation</searchLink><br /><searchLink fieldCode="DE" term="%22Functional+magnetic+resonance+imaging%22">Functional magnetic resonance imaging</searchLink><br /><searchLink fieldCode="DE" term="%22Lateral+dominance%22">Lateral dominance</searchLink><br /><searchLink fieldCode="DE" term="%22Cingulate+cortex%22">Cingulate cortex</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: While the left subgenual anterior cingulate cortex (sgACC) is a validated target for treating major depressive disorder (MDD) (e.g., with rTMS), the therapeutic relevance of the right sgACC is unknown. Given emerging evidence that treatment‐resistant depression (TRD) and non‐TRD (nTRD) may involve distinct neural circuits, a more precise, circuit‐based understanding is needed. This study, therefore, sought to determine the degree of sgACC functional lateralization and to elucidate TRD‐specific neural mechanisms, thereby informing the development of targeted neuromodulation therapies. Methods: Resting‐state fMRI (rs‐fMRI) data were acquired for 20 patients with TRD, 53 patients with nTRD, and 51 healthy controls (HCs). Analysis was performed to compare the static functional connectivity (sFC), dynamic functional connectivity (dFC), and effective connectivity via Granger causality analysis (GCA) of left and right sgACC between the three groups, followed by clinical correlation analyses. Results: Group analysis revealed significant sFC and dFC between left sgACC and temporal pole (TP), fusiform gyrus (FG), parahippocampal gyrus (PHG), and orbitofrontal cortex (OFC), and between right sgACC and cerebellum posterior lobule (CPL) and right dorsolateral prefrontal cortex (DLPFC.R). Furthermore, GCA showed increased effective connectivity between bilateral sgACC and left caudate (CAU.L), left thalamus (THA.L), right postcentral gyrus (PoCG.R), and DLPFC.L. Compared to the nTRD group the TRD group showed decreased sFC and dFC between sgACC and DLPFC and cerebellum, along with decreased effective connectivity between sgACC and CAU and DLPFC, indicating disrupted fronto‐limbic and cerebellar circuits in TRD. Conclusion: The distinct sgACC‐centered connectivity profiles of TRD and nTRD delineate a neurobiological continuum across MDD subtypes, pinpointing the sgACC, DLPFC, CAU, and cerebellum as key circuit targets for individualized neuromodulation in TRD. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Depression & Anxiety (1091-4269) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1155/da/8863773
    Languages:
      – Code: eng
        Text: English
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        PageCount: 14
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    Subjects:
      – SubjectFull: Functional connectivity
        Type: general
      – SubjectFull: Mental depression
        Type: general
      – SubjectFull: Neural circuitry
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      – SubjectFull: Neuromodulation
        Type: general
      – SubjectFull: Functional magnetic resonance imaging
        Type: general
      – SubjectFull: Lateral dominance
        Type: general
      – SubjectFull: Cingulate cortex
        Type: general
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      – TitleFull: Lateralization of the sgACC‐Based Neural Network in Treatment‐Resistant Depression.
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              Text: 3/20/2026
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              Y: 2026
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