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Plasma Apo-E mediated corticospinal tract abnormalities and suicidality in patients with major depressive disorder

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Abstract

This study aims to explore the link between Apo-E, brain white matter, and suicide in patients with major depressive disorder (MDD) to investigate the potential neuroimmune mechanisms of Apo-E that may lead to suicide. Thirty-nine patients with MDD (22 patients with suicidality) and 57 age, gender, and education-matched healthy controls participated in this study, provided plasma Apo-E samples, and underwent diffusion tensor imaging scans. Plasma Apo-E levels and white matter microstructure were analyzed among the MDD with suicidality, MDD without suicidality, and HC groups using analysis of variance with post hoc Bonferroni correction and tract-based spatial statistics (TBSS) with threshold-free cluster enhancement correction. Mediation analysis investigated the relationship between Apo-E, brain white matter, and suicidality in MDD. The MDD with suicidality subgroup had higher depressive and suicide scores, longer disease course, and lower plasma Apo-E levels than MDD without suicidality. TBSS revealed that the MDD non-suicide subgroup showed significantly increased mean diffusivity in the left corticospinal tract and body of the left corpus callosum, as well as increased axial diffusivity in the left anterior corona radiata and the right posterior thalamic radiation compared to the suicidal MDD group. The main finding was that the increased MD of the left corticospinal tract contributed to the elevated suicide score, with Apo-E mediating the effect. Preliminary result that Apo-E’s mediating role between the left corticospinal tract and the suicide factor suggests the neuroimmune mechanism of suicide in MDD. The study was registered on ClinicalTrials.gov (NCT03790085).

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Data supporting the findings of this study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was financially supported by several organizations, including the Natural Science Foundation of China (Grants 8227050387 and 82101590), the Shanghai Youth Science and Technology Stars and Outstanding Discipline Leaders Program (Grant 20XD1403100), the Western Medicine Guide Project of the Science and Technology Commission of Shanghai Municipality (Grant 19411969300) and the Project of Xuhui District Science Committee (SHXH202014).

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  1. Yi Zhang and Chen Zhang have contributed equally to this work as co-corresponding authors.

Authors and Affiliations

  1. Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Xiaoxia Lei, Xinyu Fang, Juanjuan Ren, Xinyue Teng, Chaoyue Guo, Zenan Wu, Lingfang Yu, Dandan Wang, Yan Chen, Yi Zhang & Chen Zhang

  2. Department of Psychiatry, Huaian No. 3 People’s Hospital, Huaian, Jiangsu, China

    Yunshan Zhou

  3. Department of Psychiatry, Shanghai Xuhui Mental Health Center, Shanghai, China

    Yujie Wu

  4. National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai, 200030, China

    Yi Zhang & Chen Zhang

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  1. Xiaoxia Lei
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Contributions

CZ, YZ and XL were responsible for the study concept and design. XF, JR, XT, CG, ZW, LY, DW, YC, YZ and YW contributed to the data collection. XL analyzed the data and wrote the manuscript. CZ and YZ provided critical revision of the manuscript for important intellectual content. All authors critically reviewed the content and approved the final version for publication.

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Correspondence to Yi Zhang or Chen Zhang.

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The authors declare that they have no conflict of interest.

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The Ethics Committee of the Shanghai Mental Health Center of the School of Medicine of Shanghai Jiao Tong University has approved the research protocol. All subjects were informed of the purpose of the study and provided documented informed consent. All of our investigations were conducted strictly with the Declaration of Helsinki.

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Lei, X., Fang, X., Ren, J. et al. Plasma Apo-E mediated corticospinal tract abnormalities and suicidality in patients with major depressive disorder. Eur Arch Psychiatry Clin Neurosci (2024). https://doi.org/10.1007/s00406-023-01749-w

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