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

Abstract

Background 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. Method 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. Results 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. Conclusion 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.

Identification of Key Genes and Underlying Mechanisms in Cystic Fibrosis and its Associated Complications Based on Bioinformatics Analysis of Next Generation Sequencing Data Analysis

“…Previous studies had shown that pathways include neutrophil degranulation [74], immune system [75], extracellular matrix organization [76], toll-like receptor cascades [77], cytokine signaling in immune system [78], metabolism of RNA [79] and gene expression [80] were involved in the progression of CF. NTRK3 [81], MMP9 [82], IGF2 [83], SOCS3 [84], IGFBP2 [85], SLC1A3 [86], NOS1AP [87], HP (haptoglobin) [88], TLR5 [89], ARG1 [90], NRG1 [91], RGS5 [92], LCN2 [93], TSPO (translocator protein) [94], PLAU (plasminogen activator, urokinase) [95], MME (membrane metalloendopeptidase) [96], BST1 [97], NR6A1 [98], TLR4 [99], NRN1 [100], ABCA13 [101], CTSD (cathepsin D) [102], NCAM1 [103], SIGMAR1 [104], CNR2 [105], CCR4 [106], ABCB1 [107], TIMELESS (timeless circadian regulator) [108], IRF8 [109], TXNIP (thioredoxin interacting protein) [110], SUV39H1 [111], CRY1 [112], CRY2 [113], PDCD4 [114] and MGAT5 [115] played an important role in depression and anxiety. Accumulating evidence has demonstrated that MMP9 [116], S100A12 [117], HP (haptoglobin) [118], TLR5 [119], NRG1 [120], PLAU (plasminogen activator, urokinase) [121], SLC11A1 [122], AQP9 [123], CHIT1 [124], TLR4 [125], SLC26A8 [126], CTSD (cathepsin D) [127], SERPINB1 [128], FASLG (Fas ligand) [129], SLC4A4 [130], AQP3 [131] and IRF8 [132] appears to be constitutively associated with CF .…”

Alterations in inflammatory markers after a 12-week exercise program in individuals with schizophrenia—a randomized controlled trial

“…The current study is a part of the Effect of Physical Activity on Psychosis Study (EPHAPS), approved by the Regional Committees for Medical and Health Research Ethics (trial number 2014/372), and is examining LGI and factors influencing LGI in a physical exercise intervention RCT with observer-blinded parallel group design ( 33 ). The current sample has been studied as a part of a larger cross-sectional sample ( 6 , 16 ), and in an RCT setting with a physical exercise intervention investigating effect on CRF, cognition and symptoms ( 34 – 36 ).…”

“…Inflammation is considered a cause of non-communicable diseases, such as cardiovascular disease (CVD) and type II diabetes, and is associated with schizophrenia, depression, reduced quality of life and reduced motivation (4,(6)(7)(8)(9). Thus, inflammation may represent a possible link between schizophrenia and increased risk of somatic and psychiatric comorbidity.…”

“…Recently, increased levels of suPAR have been demonstrated in individuals with schizophrenia (16,17), while a smaller study showed no difference compared to healthy controls (18). Notably, suPAR levels correlated with depressive symptoms in individuals with and without schizophrenia, making suPAR-reducing interventions interesting to pursue (6,(19)(20)(21).…”

Potential Inflammatory Biomarker in Patients with Attention Deficit Hyperactivity Disorder

“…Individual relationships of these markers with various mental disorders in perinatal and offspring outcomes, chronic states, and pre/post-treatment have been examined based on cytokines, C-reactive protein, hormones, neurotrophins, and so on. Some commonly investigated cytokine measures are summarized in Table 1 [ 12 , 40 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. When interpreting reports of individual studies, it is crucial to consider the extent to which other factors affecting peripheral cytokines are accounted for in specific analyses.…”