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Peripheral inflammatory markers associated with brain volume reduction in patients with bipolar I disorder

Published online by Cambridge University Press:  20 December 2021

Shang-Ying Tsai*
Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
Martha Sajatovic
Department of Psychiatry, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
Jung-Lung Hsu
Department of Neurology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City, Taiwan Graduate Institute of Humanities in Medicine and Research Center for Brain and Consciousness, College of Humanities And Social Sciences, Taipei Medical University, Taipei, Taiwan
Kuo-Hsuan Chung
Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
Pao-Huan Chen
Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
Yu-Jui Huang
Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
Author for correspondence: Shang-Ying Tsai, Email:



Neuroinflammation and brain structural abnormalities are found in bipolar disorder (BD). Elevated levels of cytokines and chemokines have been detected in the serum and cerebrospinal fluid of patients with BD. This study investigated the association between peripheral inflammatory markers and brain subregion volumes in BD patients.


Euthymic patients with bipolar I disorder (BD-I) aged 20–45 years underwent whole-brain magnetic resonance imaging. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), chitinase-3-like protein 1 (also known as YKL-40), fractalkine (FKN), soluble tumour necrosis factor receptor-1 (sTNF-R1), interleukin-1β, and transforming growth factor-β1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others.


We recruited 31 patients with a mean age of 29.5 years. In multivariate regression analysis, plasma level YKL-40, a chemokine, was the most common inflammatory marker among these measurements displaying significantly negative association with the volume of various brain subareas across the frontal, temporal, and parietal lobes. Higher YKL-40 and sTNF-R1 levels were both significantly associated with lower volumes of the left anterior cingulum, left frontal lobe, right superior temporal gyrus, and supramarginal gyrus. A greater number of total lifetime mood episodes were also associated with smaller volumes of the right caudate nucleus and bilateral frontal lobes.


The volume of brain regions known to be relevant to BD-I may be diminished in relation to higher plasma level of YKL-40, sTNF-R1, and more lifetime mood episodes. Macrophage and macrophage-like cells may be involved in brain volume reduction among BD-I patients.

Original Article
© The Author(s), 2021. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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