Irritable Bowel Syndrome Is Associated With Brain Health by Neuroimaging, Behavioral, Biochemical, and Genetic Analyses

Zeyu Li; Qing Ma; Yueting Deng; Edmund T Rolls; Chun Shen; Yuzhu Li; Wei Zhang; Shitong Xiang; Christelle Langley; Barbara J Sahakian; Trevor W Robbins; Jin-Tai Yu; Jianfeng Feng; Wei Cheng

doi:10.1016/j.biopsych.2023.12.024

Irritable Bowel Syndrome Is Associated With Brain Health by Neuroimaging, Behavioral, Biochemical, and Genetic Analyses

Biol Psychiatry. 2024 Jan 8:S0006-3223(24)00027-1. doi: 10.1016/j.biopsych.2023.12.024. Online ahead of print.

Authors

Affiliations

¹ Institute of Science and Technology for Brain-Inspired Intelligence, Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
² Institute of Science and Technology for Brain-Inspired Intelligence, Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China; Department of Computer Science, University of Warwick, Coventry, United Kingdom; Oxford Centre for Computational Neuroscience, Oxford, United Kingdom. Electronic address: Edmund.Rolls@oxcns.org.
³ Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
⁴ Institute of Science and Technology for Brain-Inspired Intelligence, Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
⁵ Institute of Science and Technology for Brain-Inspired Intelligence, Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China; Department of Psychology, University of Cambridge, Cambridge, United Kingdom.
⁶ Institute of Science and Technology for Brain-Inspired Intelligence, Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China; Department of Computer Science, University of Warwick, Coventry, United Kingdom; Fudan ISTBI-ZJNU Algorithm Centre for Brain-inspired Intelligence, Zhejiang Normal University, Jinhua, China. Electronic address: jianfeng64@gmail.com.
⁷ Institute of Science and Technology for Brain-Inspired Intelligence, Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China; Fudan ISTBI-ZJNU Algorithm Centre for Brain-inspired Intelligence, Zhejiang Normal University, Jinhua, China. Electronic address: wcheng@fudan.edu.cn.

PMID: 38199582
DOI: 10.1016/j.biopsych.2023.12.024

Abstract

Background: Irritable bowel syndrome (IBS) interacts with psychopathology in a complex way; however, little is known about the underlying brain, biochemical, and genetic mechanisms.

Methods: To clarify the phenotypic and genetic associations between IBS and brain health, we performed a comprehensive retrospective cohort study on a large population. Our study included 171,104 participants from the UK Biobank who underwent a thorough assessment of IBS, with the majority also providing neuroimaging, behavioral, biochemical, and genetic information. Multistage linked analyses were conducted, including phenome-wide association analysis, polygenic risk score calculation, and 2-sample Mendelian randomization analysis.

Results: The phenome-wide association analysis showed that IBS was linked to brain health problems, including anxiety and depression, and poor cognitive performance. Significantly lower brain volumes associated with more severe IBS were found in key areas related to emotional regulation and higher-order cognition, including the medial orbitofrontal cortex/ventromedial prefrontal cortex, anterior insula, anterior and mid-cingulate cortices, dorsolateral prefrontal cortex, and hippocampus. Higher triglycerides, lower high-intensity lipoprotein, and lower platelets were also related (p < 1 × 10^-10) to more severe IBS. Finally, Mendelian randomization analyses demonstrated potential causal relationships between IBS and brain health and indicated possible mediating effects of dyslipidemia and inflammation.

Conclusions: For the first time, this study provides a comprehensive understanding of the relationship between IBS and brain health phenotypes, integrating perspectives from neuroimaging, behavioral performance, biochemical factors, and genetics, which is of great significance for clinical applications to potentially address brain health impairments in patients with IBS.

Keywords: Brain health; Depression; Irritable bowel syndrome; Mendelian randomization; Neuroimaging; UK Biobank.