Cerebrospinal Fluid Inflammatory Cytokine Levels in Patients With Major Psychiatric Disorders: A Multiplex Immunoassay Study.

Shinsuke Hidese,Hiroshi Kunugi,Junko Matsuo,Ryo Matsumura,Miho Ota,Yuuki Yokota,Takuya Tsumagari,Daimei Sasayama,Sumiko Yoshida,Kotaro Hattori,Ikki Ishida,Tomoko Miyakawa

doi:10.3389/fphar.2020.594394

Abstract

Aim: Accumulating evidence suggests that neural inflammation plays an important role in psychiatric disorders. We aimed to identify inflammatory cytokines involved in the pathophysiology of such disorders by quantifying them in cerebrospinal fluid (CSF) samples from a large sample of patients with major psychiatric disorders and healthy controls. Methods: The subjects included 94 patients with schizophrenia, 68 with bipolar disorder, 104 with major depressive disorder, and 118 healthy controls, matched for age, sex, and ethnicity (Japanese). Lumbar puncture was performed to collect these CSF samples. A multiplex immunoassay was then performed to measure CSF cytokine levels using magnetic on-bead antibody conjugation for 19 inflammatory cytokines. Results: CSF interferon-β level was significantly higher in total psychiatric patients than in healthy controls (corrected p = 0.000029). In diagnostic group comparisons, CSF interferon-β level was significantly higher in patients with schizophrenia, or bipolar disorder (corrected p = 0.000047 or 0.0034) than in healthy controls. Conclusion: We present novel evidence that CSF IFN-β level showed prominent statistical differences between psychiatric groups and healthy controls. This suggests IFN-β as the most important player among the 19 cytokines tested here in the inflammation-related pathophysiology of major psychiatric disorders.

Highlights

There were no significant differences in the distributions of age and sex, while body mass index (BMI) and education level were significantly higher and lower, respectively, in patients with schizophrenia than in healthy controls
Correlations between Cerebrospinal fluid (CSF) cytokine levels and clinical variables in patients with schizophrenia, bipolar disorder (BD), or major depressive disorder (MDD) and healthy controls are shown in Supplementary Tables S1–S4, respectively
Even when comparing across all four diagnostic groups, we found that CSF IFN-β level was higher in patients with schizophrenia and in those with BD, in this order, than in healthy controls

Summary

Introduction

Inflammation has been suggested to play a key role in the pathogenesis and pathophysiology of psychiatric disorders (Khandaker et al, 2017; Bauer and Teixeira, 2018), including schizophrenia (Horvath and Mirnics, 2014; Na et al, 2014; Muller et al, 2015; Khandaker and Dantzer, 2016; Muller, 2018), bipolar disorder (BD) (Rosenblat and McIntyre, 2015; Walther et al, 2017), and major depressive disorder (MDD) (SpernerUnterweger et al, 2014; Kunugi et al, 2015; Adzic et al, 2018; Misiak et al, 2018). In the pathophysiology of these disorders, a bidirectional interplay between the brain and the immune system has been suggested (Dantzer, 2018). Our research group has reported elevations in inflammation-related molecules in the CSF of patients with schizophrenia, BD, or MDD using the enzymelinked immunosorbent assays (Sasayama et al, 2013; Hattori et al, 2015; Ishii et al, 2018). There are many other candidate molecules related to inflammation

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Discussion

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