Inflammation is associated with decreased functional connectivity of insula in unmedicated bipolar disorder

Pan Chen; Feng Chen; Guanmao Chen; Shuming Zhong; JiaYing Gong; Hui Zhong; Tao Ye; Guixian Tang; Jurong Wang; Zhenye Luo; Zhangzhang Qi; Yanbin Jia; Hengwen Yang; Zhinan Yin; Li Huang; Ying Wang

doi:10.1016/j.bbi.2020.07.004

Inflammation is associated with decreased functional connectivity of insula in unmedicated bipolar disorder

Brain Behav Immun. 2020 Oct:89:615-622. doi: 10.1016/j.bbi.2020.07.004. Epub 2020 Jul 17.

Authors

Pan Chen¹, Feng Chen¹, Guanmao Chen¹, Shuming Zhong², JiaYing Gong³, Hui Zhong⁴, Tao Ye⁵, Guixian Tang¹, Jurong Wang¹, Zhenye Luo¹, Zhangzhang Qi¹, Yanbin Jia², Hengwen Yang⁶, Zhinan Yin⁴, Li Huang¹, Ying Wang⁷

Affiliations

¹ Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Institute of Molecular and Functional Imaging, Jinan University, Guangzhou 510630, China.
² Department of Psychiatry, First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
³ Institute of Molecular and Functional Imaging, Jinan University, Guangzhou 510630, China; Department of Radiology, Six Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China.
⁴ Biomedical Translational Research Institute, Jinan University, Guangzhou 510630, China.
⁵ Clinical Laboratory Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
⁶ Biomedical Translational Research Institute, Jinan University, Guangzhou 510630, China; Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai 519000, China.
⁷ Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Institute of Molecular and Functional Imaging, Jinan University, Guangzhou 510630, China. Electronic address: johneil@vip.sina.com.

PMID: 32688026
DOI: 10.1016/j.bbi.2020.07.004

Abstract

Background: Systemic inflammation and immune dysregulation have been considered as risk factors in the pathophysiology of mood disorders including bipolar disorder (BD). Previous neuroimaging studies have demonstrated metabolic, structural and functional abnormalities in the insula in BD, proposed that the insula played an important role in BD. We herein aimed to explore neural mechanisms underlying inflammation-induced in the insular subregions functional connectivity (FC) in patients with BD.

Methods: Brain resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 41 patients with unmedicated BD II (current episode depressed), 68 healthy controls (HCs). Three pairs of insular seed regions were selected: the bilateral anterior insula (AI), the bilateral middle insula (MI) and the bilateral posterior insula (PI), and calculated the whole-brain FC for each subregion. Additionally, the serum levels of pro-inflammatory cytokines in patients and HCs, including IL-6 and TNF-α, were detected. Then the partial correlation coefficients between the abnormal insular subregions FC values and pro-inflammatory cytokines levels in patients with BD II depression were calculated.

Results: The BD II depression group exhibited decreased FC between the right PI and the left postcentral gyrus, and increased FC between the left AI and the bilateral insula (extended to the right putamen) when compared with the HC group. Moreover, the patients with BD II depression showed higher IL-6 and TNF-α levels than HCs, and IL-6 level was negatively correlated with FC of the right PI to the left postcentral gyrus.

Conclusions: Our results demonstrated that abnormal FC between the bilateral insula, and between the insula and sensorimotor areas in BD. Moreover, disrupted FC between the insula and sensorimotor areas was associated with elevated pro-inflammatory cytokine levels of IL-6 in BD.

Keywords: Bipolar disorder; Functional connectivity; Functional magnetic resonance imaging; Inflammation; Insula.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bipolar Disorder* / diagnostic imaging
Cerebral Cortex / diagnostic imaging
Humans
Inflammation / diagnostic imaging
Magnetic Resonance Imaging
Neuroimaging