| Title: | Multimodal fusion of brain imaging and proteomics reveals a brain-body pathway linking depression and metabolic dysfunction |
| Journal: | Psychological Medicine |
| Published: | 13 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42124391/ |
| DOI: | https://doi.org/10.1017/s003329172610436x |
| URL: | ~Ehttps://www.cambridge.org/core/services/aop-cambridge-core/content/view/3099497C4193C8E008EA395F9CFF61C6/S003329172610436Xa.pdf/div-class-title-multimodal-fusion-of-brain-imaging-and-proteomics-reveals-a-brain-body-pathway-linking-depression-and-metabolic-dysfunction-div.pdf~ |
Publication 20080
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Abstract
BACKGROUND: Depression is associated with pathological dysregulations affecting both the brain and the body, with the latter being reflected in plasma proteins. While plasma protein signatures of depression have been increasingly recognized, a holistic examination of interactions with brain features is lacking.</p>
METHODS: Leveraging data from 3,966 UK Biobank participants, we identified a multimodal neuroimaging-plasma protein component of depression (NeuroPro-Dep) by integrating plasma proteins and five brain modalities via an ICD-10 diagnosis-constrained multimodal fusion approach.</p>
RESULTS: Notably, NeuroPro-Dep demonstrates detectable associations with depression symptoms across datasets from diverse populations, underscoring its clinical potential. This capability is anchored in its five brain modalities alterations, including hippocampal atrophy, reduced cortical sensorimotor network functional connectivity, and impaired internetwork structural connectivity of the frontoparietal network. The multimodal neuroimaging-derived plasma protein modality of NeuroPro-Dep is enriched in metabolic pathways, as further supported by association analysis linking this modality to body mass index (BMI), type 2 diabetes, and other metabolic indicators. Crucially, two-step Mendelian randomization analysis revealed that the NeuroPro-Dep plasma protein modality exerts a causal effect on depression through BMI (plasma protein to BMI: or=0.28, p=0.035; BMI to depression: or=1.14, p=4.37×10-11).</p>
CONCLUSIONS: Overall, this study underscores metabolic dysfunction as a bridge between brain changes, depression, and physical diseases, while providing a novel multimodal biological signature and valuable insights that may inform future treatment strategies.</p>
17 Keywords
- Adult
- Aged
- Blood Proteins
- Body Mass Index
- Brain
- Depression
- Diabetes Mellitus, Type 2
- Female
- Humans
- Magnetic Resonance Imaging
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Multimodal Imaging
- Neuroimaging
- Proteomics
- United Kingdom
17 Authors
- Zhengxu Lian
- Zhaowen Liu
- Huaxin Fan
- Jiazheng Wang
- Kai Zhang
- Yu Liu
- Nanyu Kuang
- Gechang Yu
- Wei Cheng
- Benjamin Becker
- Barbara J. Sahakian
- Trevor W. Robbins
- Vince D. Calhoun
- Jing Sui
- Xinran Wu
- Jie Zhang
- Jianfeng Feng
1 Application
| Application ID | Title |
|---|---|
| 19542 | Identifying multi-level biomarkers and disease mechanisms for major mental disorders |
Enabling scientific discoveries that improve human health