Reduced levels of circulating adhesion molecules in adolescents with early-onset psychosis

Wedervang‐Resell, Kirsten; Ueland, Thor; Aukrust, Pål; Friis, Svein; Holven, Kirsten B.; Johannessen, Cecilie; Lekva, Tove; Lonning, Vera; Smelror, Runar; Szabó, Attila; Andreassen, Ole A.; Myhre, Anne Margrethe; Agartz, Ingrid

doi:10.1038/s41537-020-00112-5

Cited by 12 publications

(5 citation statements)

References 67 publications

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“…Additionally, we found no differences between subgroups for AAO or DOI, which could suggest a common cognitive and inflammatory/immune activation pattern independent of illness stage. This supports findings of cognitive deficits and increased inflammation in both first-episode psychosis and chronic illness [41,99]. Notably, differences across studies based on the selection bias of inflammatory/immune markers and cognitive outcomes could contribute to differing observations from subgroup-studies.…”

Section: Discussionsupporting

confidence: 81%

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

et al. 2022

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A potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate relationships between peripheral inflammatory/immune-related markers and cognitive domains are unclear, and many studies do not account for inter-individual variance in both cognitive functioning and inflammatory/immune status. This study aimed to investigate covariance patterns between inflammatory/immune-related markers and cognitive domains and further elucidate heterogeneity in a large SMI and healthy control (HC) cohort (SZ = 343, BD = 289, HC = 770). We applied canonical correlation analysis (CCA) to identify modes of maximum covariation between a comprehensive selection of cognitive domains and inflammatory/immune markers. We found that poor verbal learning and psychomotor processing speed was associated with higher levels of interleukin-18 system cytokines and beta defensin 2, reflecting enhanced activation of innate immunity, a pattern augmented in SMI compared to HC. Applying hierarchical clustering on covariance patterns identified by the CCA revealed a high cognition—low immune dysregulation subgroup with predominantly HC (24% SZ, 45% BD, 74% HC) and a low cognition—high immune dysregulation subgroup predominantly consisting of SMI patients (76% SZ, 55% BD, 26% HC). These subgroups differed in IQ, years of education, age, CRP, BMI (all groups), level of functioning, symptoms and defined daily dose (DDD) of antipsychotics (SMI cohort). Our findings suggest a link between cognitive impairment and innate immune dysregulation in a subset of individuals with severe mental illness.

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Section: Discussionsupporting

confidence: 81%

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

et al. 2022

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“…There is conflicting evidence of VCAM-1 ( Futtrup et al, 2020 ; Nguyen et al, 2018 ; Stefanovic et al, 2016 ); however, both ICAM-1 and VCAM-1 may be related to manic episodes ( Turan et al, 2014 ). In a study from our centre of adolescent participants with early-onset psychosis ( Wedervang-Resell et al, 2020 ), reduced levels of PSEL and VCAM-1 and no significant alterations of ICAM-1, MadCAM-1, JAMA or NCAD, were found. While both studies suggest involvement of CAMs in SMD pathophysiology, differences indicate the need of examining temporal patterns as well as potential variations between subgroups.…”

Section: Discussionmentioning

confidence: 94%

Composite immune marker scores associated with severe mental disorders and illness course

Ormerod¹,

Ueland²,

Werner³

et al. 2022

Brain, Behavior, & Immunity - Health

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“…Abnormalities of these elements have been reported in schizophrenia: reduced focal adhesion in patient-derived cells [64], negative correlation between expression of tight junction mRNAs and disease duration [65], and loss of adherens junctions in human iPSC-derived neural progenitors carrying a risk variant [66]. Altered levels of immune cell adhesion molecules in the plasma of schizophrenia patients also suggested the link of disrupted cell adhesion to abnormal immunomodulation in the disorder as discussed previously [67,68].…”

Section: Discussionmentioning

confidence: 72%

Network-based drug repurposing for schizophrenia

Truong,

Liu,

Panizzutti

et al. 2024

Neuropsychopharmacol.

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Despite recent progress, the challenges in drug discovery for schizophrenia persist. However, computational drug repurposing has gained popularity as it leverages the wealth of expanding biomedical databases. Network analyses provide a comprehensive understanding of transcription factor (TF) regulatory effects through gene regulatory networks, which capture the interactions between TFs and target genes by integrating various lines of evidence. Using the PANDA algorithm, we examined the topological variances in TF-gene regulatory networks between individuals with schizophrenia and healthy controls. This algorithm incorporates binding motifs, protein interactions, and gene co-expression data. To identify these differences, we subtracted the edge weights of the healthy control network from those of the schizophrenia network. The resulting differential network was then analysed using the CLUEreg tool in the GRAND database. This tool employs differential network signatures to identify drugs that potentially target the gene signature associated with the disease. Our analysis utilised a large RNA-seq dataset comprising 532 post-mortem brain samples from the CommonMind project. We constructed co-expression gene regulatory networks for both schizophrenia cases and healthy control subjects, incorporating 15,831 genes and 413 overlapping TFs. Through drug repurposing, we identified 18 promising candidates for repurposing as potential treatments for schizophrenia. The analysis of TF-gene regulatory networks revealed that the TFs in schizophrenia predominantly regulate pathways associated with energy metabolism, immune response, cell adhesion, and thyroid hormone signalling. These pathways represent significant targets for therapeutic intervention. The identified drug repurposing candidates likely act through TF-targeted pathways. These promising candidates, particularly those with preclinical evidence such as rimonabant and kaempferol, warrant further investigation into their potential mechanisms of action and efficacy in alleviating the symptoms of schizophrenia.

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Reduced levels of circulating adhesion molecules in adolescents with early-onset psychosis

Cited by 12 publications

References 67 publications

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

Composite immune marker scores associated with severe mental disorders and illness course

Network-based drug repurposing for schizophrenia

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