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Association between resting-state functional connectivity of amygdala subregions and peripheral pro-inflammation cytokines levels in bipolar disorder

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Abstract

The pathophysiological mechanisms of bipolar disorder (BD) are not completely known, and systemic inflammation and immune dysregulation are considered as risk factors. Previous neuroimaging studies have proved metabolic, structural and functional abnormalities of the amygdala in BD, suggesting the vital role of amygdala in BD patients. This study aimed to test the underlying neural mechanism of inflammation-induced functional connectivity (FC) in the amygdala subregions of BD patients. Resting-state functional MRI (rs-fMRI) was used to delineate the amygdala FC from two pairs of amygdala seed regions (the bilateral lateral and medial amygdala) in 51 unmedicated BD patients and 69 healthy controls (HCs). The levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured in the serum. The correlation between abnormal levels of pro-inflammatory cytokines and FC values were calculated in BD patients. The BD group exhibited decreased FC between the right medial amygdala and bilateral medial frontal cortex (MFC), and decreased FC between the left medial amygdala and the left temporal pole (TP), right orbital inferior frontal gyrus compared with HCs. The BD patients had higher levels of TNF-α than HCs. Correlation analysis showed negative correlation between the TNF-α level and abnormal FC of the right medial amygdala-bilateral MFC; and negative correlation between TNF-α levels and abnormal FC of the left medial amygdala-left TP in BD group. These findings suggest that dysfunctional and immune dysregulation between the amygdala and the frontotemporal circuitry might play a critical role in the pathogenesis of BD.

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

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Funding

The study was supported by grants from the National Natural Science Foundation of China (81671670, 81971597 and 82102003); Project in Basic Research and Applied Basic Research in General Colleges and Universities of Guangdong, China (2018KZDXM009); National Key Research and Development Project (2020YFC2005700). The funding organizations play no further role in study design, data collection, analysis and interpretation and paper writing.

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Author notes

  1. Jiaying Gong and Guanmao Chen contributed equally to this work.

Authors and Affiliations

  1. Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Jiaying Gong, Guanmao Chen, Feng Chen, Pan Chen, Guixian Tang, Jurong Wang, Zhenye Luo, Zhangzhang Qi, Li Huang & Ying Wang

  2. Department of Radiology, Six Affiliated Hospital of Sun Yat-sen University, 510655, Guangzhou, China

    Jiaying Gong

  3. Institute of Molecular and Functional Imaging, Jinan University, 510630, Guangzhou, China

    Guanmao Chen, Feng Chen, Pan Chen, Guixian Tang, Jurong Wang, Zhenye Luo, Zhangzhang Qi, Li Huang & Ying Wang

  4. Department of Psychiatry, First Affiliated Hospital of Jinan University, 510630, Guangzhou, China

    Shuming Zhong, Shunkai Lai & Yanbin Jia

  5. Biomedical Translational Research Institute, Jinan University, 510630, Guangzhou, China

    Hui Zhong

Authors
  1. Jiaying Gong
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  2. Guanmao Chen
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  3. Feng Chen
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  4. Shuming Zhong
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  5. Pan Chen
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  9. Jurong Wang
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  13. Li Huang
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  14. Ying Wang
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Contributions

Ying Wang designed the study; Jiaying Gong, Ying Wang contributed to data sources and study selection; Jiaying Gong, Guanmao Chen, Feng Chen, Shuming Zhong, Pan Chen, Hui Zhong, Shunkai Lai, Guixian Tang, Jurong Wang, Zhenye Luo, Zhangzhang Qi, Yanbin Jia contributed to data acquisition; Guanmao Chen, Feng Chen contributed to data analysis; Jiaying Gong wrote the manuscript; Pan Chen, Feng Chen, Jiaying Gong, Guanmao Chen, Feng Chen, Hui Zhong, Li Huang, Ying Wang revised the manuscript. All authors contributed to and have approved the final manuscript. We thank all the authors of the included studies who responded to our requests for further information.

Corresponding author

Correspondence to Ying Wang.

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This study was approved by the Ethics Committee of First Affiliated Hospital of Jinan University, Guangzhou, China.

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Gong, J., Chen, G., Chen, F. et al. Association between resting-state functional connectivity of amygdala subregions and peripheral pro-inflammation cytokines levels in bipolar disorder. Brain Imaging and Behavior 16, 1614–1626 (2022). https://doi.org/10.1007/s11682-022-00636-7

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