Exploring low grade inflammation by soluble urokinase plasminogen activator receptor levels in schizophrenia: a sex-dependent association with depressive symptoms

Therese Torgersen Bigseth,Morten Lindberg,Jon Mordal,Nils Eiel Steen,Thor Ueland,Ragnhild Sørum Falk,Ole Andreas Andreassen,Tom Langerud Holmen,Jens Egeland,Jimmi Nielsen,Gry Bang-Kittilsen,Torkel Vang,John Abel Engh,Mats Fredriksen,Eivind Andersen

doi:10.1186/s12888-021-03522-6

Abstract

BackgroundThere is evidence of increased low grade inflammation (LGI) in schizophrenia patients. However, the inter-individual variation is large and the association with demographic, somatic and psychiatric factors remains unclear. Our aim was to explore whether levels of the novel LGI marker soluble urokinase plasminogen activator receptor (suPAR) were associated with clinical factors in schizophrenia and if such associations were sex-dependent.MethodIn this observational study a total of 187 participants with schizophrenia (108 males, 79 females) underwent physical examination and assessment with clinical interviews (Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Alcohol Use Disorder Identification Test (AUDIT), and Drug Use Disorder Identification Test (DUDIT)). Blood levels of suPAR, glucose, lipids, and high sensitivity C-reactive protein (hsCRP) were determined and body mass index (BMI) calculated. Multivariable linear regression analyses were used adjusting for confounders, and sex interaction tested in significant variables.ResultsAdjusting for sex, age, current tobacco smoking and BMI, we found that levels of hsCRP and depressive symptoms (CDSS) were positively associated with levels of suPAR (p < 0.001). The association between suPAR and CDSS score was significant in females (p < 0.001) but not in males. Immune activation measured by hsCRP was not associated with depressive symptoms after adjusting for BMI.ConclusionOur findings indicate that increased suPAR levels are associated with depressive symptoms in females with schizophrenia, suggesting aberrant immune activation in this subgroup. Our results warrant further studies, including longitudinal follow-up of suPAR levels in schizophrenia and experimental studies of mechanisms.

Highlights

There is evidence of increased low grade inflammation (LGI) in schizophrenia patients
Adjusting for sex, age, current tobacco smoking and body mass index (BMI), we found that levels of high sensitivity C-reactive protein (hsCRP) and depressive symptoms (CDSS) were positively associated with levels of soluble urokinase plasminogen activator receptor (suPAR) (p < 0.001)
Our findings indicate that increased suPAR levels are associated with depressive symptoms in females with schizophrenia, suggesting aberrant immune activation in this subgroup

Summary

Introduction

There is evidence of increased low grade inflammation (LGI) in schizophrenia patients. Involvement of the immune system in the pathogenesis of schizophrenia has been investigated for several decades [1]. In this regard, immune-mediated mechanisms seem to be relevant in the prenatal stage and through childhood and in adolescence and adulthood [2, 3]. Immune-mediated mechanisms seem to be relevant in the prenatal stage and through childhood and in adolescence and adulthood [2, 3] Immune disorders such as nonneurological autoimmune diseases are associated with increased risk of psychosis [4]. Analyses of postmortem endothelial cells from schizophrenia patients with increased inflammatory burden have revealed transcriptional alterations associated with endothelial cell dysregulation [10]

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