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Prefrontal Structural Asymmetry Mediates Body Mass Index and Treatment Response in Major Depressive Disorder.

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Title: Prefrontal Structural Asymmetry Mediates Body Mass Index and Treatment Response in Major Depressive Disorder.
Authors: Qiao, Kaini (AUTHOR), Zang, Zhenxiang (AUTHOR), Wang, Yun (AUTHOR), Chen, Xiongying (AUTHOR), Liu, Ke (AUTHOR), Zhang, Zhifang (AUTHOR), Liu, Rui (AUTHOR), Li, Dong (AUTHOR), Luo, Yanting (AUTHOR), Xiao, Le (AUTHOR), Zhu, Xuequan (AUTHOR), Zhou, Jingjing (AUTHOR), Yang, Zhi (AUTHOR), Wang, Gang (AUTHOR), Stoyanov, Drozdstoy (AUTHOR)
Source: Depression & Anxiety (1091-4269). 5/25/2026, Vol. 2026, p1-14. 14p.
Subjects: Body mass index, Prefrontal cortex, Mental depression, Antidepressants, Brain cortical thickness, Gender differences (Psychology), Treatment effectiveness, Computer-assisted image analysis (Medicine)
Abstract: Background: Elevated body mass index (BMI) predicts poor treatment response in major depressive disorder (MDD), yet the neurobiological mechanisms underlying this association remain poorly understood. Cortical thickness asymmetry has been proposed as a structural correlate of affective regulation and may represent a pathway through which metabolic factors influence treatment outcomes. We investigated whether BMI‐related alterations in prefrontal cortical asymmetry mediate antidepressant treatment resistance in MDD. Methods: We analyzed baseline structural MRI (sMRI) and 12‐week clinical outcome data from 312 adults with MDD across a discovery cohort (n = 107) and an independent replication cohort (n = 205). Treatment response was operationalized as absolute reduction in Hamilton depression rating scale (HAMD‐17) scores. Cortical thickness asymmetry indices were derived from regional parcellations. Associations between BMI and asymmetry were examined using linear regression models; mediation analyses tested whether BMI‐related asymmetry statistically mediates the link between higher BMI and reduced treatment response. Sex‐stratified analyses were conducted to identify divergent pathways. Results: Across both cohorts, higher BMI was consistently associated with greater leftward cortical thickness asymmetry in the prefrontal cortex (PFC). This structural asymmetry significantly mediated the relationship between BMI and poorer treatment response. Sex‐stratified analyses revealed additional female‐specific mediation through prefrontal opercular regions, with no corresponding effect in males. Transcriptomic annotation of implicated regions identified enrichment for genes involved in metabolic and cytoplasmic signaling pathways. Conclusions: BMI‐associated leftward prefrontal asymmetry statistically mediates antidepressant resistance in MDD via both a sex‐shared structural pathway and a female‐specific opercular circuit. These findings suggest that metabolic factors may influence treatment outcomes partly through hemispheric structural imbalance in prefrontal regions and position cortical thickness asymmetry as a candidate neuroimaging biomarker for patient stratification in precision psychiatry. [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: Prefrontal Structural Asymmetry Mediates Body Mass Index and Treatment Response in Major Depressive Disorder.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Qiao%2C+Kaini%22">Qiao, Kaini</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zang%2C+Zhenxiang%22">Zang, Zhenxiang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Yun%22">Wang, Yun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Xiongying%22">Chen, Xiongying</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Ke%22">Liu, Ke</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Zhifang%22">Zhang, Zhifang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Rui%22">Liu, Rui</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Dong%22">Li, Dong</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Luo%2C+Yanting%22">Luo, Yanting</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xiao%2C+Le%22">Xiao, Le</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhu%2C+Xuequan%22">Zhu, Xuequan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhou%2C+Jingjing%22">Zhou, Jingjing</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yang%2C+Zhi%22">Yang, Zhi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Gang%22">Wang, Gang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Stoyanov%2C+Drozdstoy%22">Stoyanov, Drozdstoy</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Depression+%26+Anxiety+%281091-4269%29%22">Depression & Anxiety (1091-4269)</searchLink>. 5/25/2026, Vol. 2026, p1-14. 14p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Body+mass+index%22">Body mass index</searchLink><br /><searchLink fieldCode="DE" term="%22Prefrontal+cortex%22">Prefrontal cortex</searchLink><br /><searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Antidepressants%22">Antidepressants</searchLink><br /><searchLink fieldCode="DE" term="%22Brain+cortical+thickness%22">Brain cortical thickness</searchLink><br /><searchLink fieldCode="DE" term="%22Gender+differences+%28Psychology%29%22">Gender differences (Psychology)</searchLink><br /><searchLink fieldCode="DE" term="%22Treatment+effectiveness%22">Treatment effectiveness</searchLink><br /><searchLink fieldCode="DE" term="%22Computer-assisted+image+analysis+%28Medicine%29%22">Computer-assisted image analysis (Medicine)</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Elevated body mass index (BMI) predicts poor treatment response in major depressive disorder (MDD), yet the neurobiological mechanisms underlying this association remain poorly understood. Cortical thickness asymmetry has been proposed as a structural correlate of affective regulation and may represent a pathway through which metabolic factors influence treatment outcomes. We investigated whether BMI‐related alterations in prefrontal cortical asymmetry mediate antidepressant treatment resistance in MDD. Methods: We analyzed baseline structural MRI (sMRI) and 12‐week clinical outcome data from 312 adults with MDD across a discovery cohort (n = 107) and an independent replication cohort (n = 205). Treatment response was operationalized as absolute reduction in Hamilton depression rating scale (HAMD‐17) scores. Cortical thickness asymmetry indices were derived from regional parcellations. Associations between BMI and asymmetry were examined using linear regression models; mediation analyses tested whether BMI‐related asymmetry statistically mediates the link between higher BMI and reduced treatment response. Sex‐stratified analyses were conducted to identify divergent pathways. Results: Across both cohorts, higher BMI was consistently associated with greater leftward cortical thickness asymmetry in the prefrontal cortex (PFC). This structural asymmetry significantly mediated the relationship between BMI and poorer treatment response. Sex‐stratified analyses revealed additional female‐specific mediation through prefrontal opercular regions, with no corresponding effect in males. Transcriptomic annotation of implicated regions identified enrichment for genes involved in metabolic and cytoplasmic signaling pathways. Conclusions: BMI‐associated leftward prefrontal asymmetry statistically mediates antidepressant resistance in MDD via both a sex‐shared structural pathway and a female‐specific opercular circuit. These findings suggest that metabolic factors may influence treatment outcomes partly through hemispheric structural imbalance in prefrontal regions and position cortical thickness asymmetry as a candidate neuroimaging biomarker for patient stratification in precision psychiatry. [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.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=194014803
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1155/da/9924894
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 14
        StartPage: 1
    Subjects:
      – SubjectFull: Body mass index
        Type: general
      – SubjectFull: Prefrontal cortex
        Type: general
      – SubjectFull: Mental depression
        Type: general
      – SubjectFull: Antidepressants
        Type: general
      – SubjectFull: Brain cortical thickness
        Type: general
      – SubjectFull: Gender differences (Psychology)
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      – SubjectFull: Treatment effectiveness
        Type: general
      – SubjectFull: Computer-assisted image analysis (Medicine)
        Type: general
    Titles:
      – TitleFull: Prefrontal Structural Asymmetry Mediates Body Mass Index and Treatment Response in Major Depressive Disorder.
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            – D: 25
              M: 05
              Text: 5/25/2026
              Type: published
              Y: 2026
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