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

• Published in: BMC psychiatry Vol. 21; no. 1; p. 527
• Main Authors: Bigseth, Therese Torgersen, Engh, John Abel, Egeland, Jens, Andersen, Eivind, Andreassen, Ole Andreas, Bang-Kittilsen, Gry, Falk, Ragnhild Sørum, Holmen, Tom Langerud, Lindberg, Morten, Mordal, Jon, Nielsen, Jimmi, Steen, Nils Eiel, Ueland, Thor, Vang, Torkel, Fredriksen, Mats
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.10.2021; BioMed Central; BMC
• Subjects: Basale medisinske, odontologiske og veterinærmedisinske fag: 710; Basic medical, dental and veterinary science disciplines: 710; Biomarkers; Blood levels; Body mass index; C-reactive protein; C-Reactive Protein - analysis; Complications and side effects; CRP; Demographic aspects; Depression; Depression - complications; Depression, Mental; Development and progression; Female; Females; Gender differences; Genetic aspects; Health aspects; Humans; Immune response; Inflammation; Lipids; Male; Medical disciplines: 700; Medisinske Fag: 700; Mental depression; Mental disorders; Psychiatry; Receptors, Urokinase Plasminogen Activator; Risk factors; Schizophrenia; Schizophrenia - complications; Sex; suPAR; Tissue plasminogen activator; Tobacco smoking; U-Plasminogen activator; Urokinase; VDP; Norway; United States > US; CRP; Urokinase; Biomarker; Sex-difference; Immunesystem; suPAR; Schizophrenia; Depression; Inflammation
• ISSN: 1471-244X; 1471-244X
• DOI: 10.1186/s12888-021-03522-6

There 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. In 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. Adjusting 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. Our 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.