Classification of Psychoses Based on Immunological Features: A Machine Learning Study in a Large Cohort of First-Episode and Chronic Patients

Enrico, Paolo; Delvecchio, Giuseppe; Turtulici, Nunzio; Pigoni, Alessandro; Villa, Filippo Maria; Perlini, Cinzia; Rossetti, Maria Gloria; Lasalvia, Antonio; Bonetto, Chiara; Scocco, Paolo; D’Agostino, Armando; Torresani, Stefano; Imbesi, Massimiliano; Bellini, F.; Veronese, Angela; Bocchio-Chiavetto, Luisella; Gennarelli, Massimo; Balestrieri, Matteo; Colombo, Gualtiero I.; Finardi, Annamaria; Ruggeri, Mirella; Furlan, Roberto; Brambilla, Paolo

doi:10.1093/schbul/sbaa190

Cited by 13 publications

(7 citation statements)

References 62 publications

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“…There are studies using inflammation-profiling approaches to stratify patients by level of inflammation ( 204 , 207 – 210 ). For example, a recent study showed that using data on mRNA transcript levels of 56 immune genes using machine learning algorithms can distinguish between people with first-episode psychosis, chronic psychosis, and controls with >80% accuracy ( 210 ). The OPTiMiSE cohort study showed that uncontrolled clustering allowed the identification of clinical subtypes of first-episode psychosis patients ( 207 ).…”

Section: Usefulness Of Immunological Data In Psychiatric Clinical Pra...mentioning

confidence: 99%

Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

et al. 2022

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The immune system is generally known to be the primary defense mechanism against pathogens. Any pathological conditions are reflected in anomalies in the immune system parameters. Increasing evidence suggests the involvement of immune dysregulation and neuroinflammation in the pathogenesis of schizophrenia. In this systematic review, we summarized the available evidence of abnormalities in the immune system in schizophrenia. We analyzed impairments in all immune system components and assessed the level of bias in the available evidence. It has been shown that schizophrenia is associated with abnormalities in all immune system components: from innate to adaptive immunity and from humoral to cellular immunity. Abnormalities in the immune organs have also been observed in schizophrenia. Evidence of increased C-reactive protein, dysregulation of cytokines and chemokines, elevated levels of neutrophils and autoantibodies, and microbiota dysregulation in schizophrenia have the lowest risk of bias. Peripheral immune abnormalities contribute to neuroinflammation, which is associated with cognitive and neuroanatomical alterations and contributes to the pathogenesis of schizophrenia. However, signs of severe inflammation are observed in only about 1/3 of patients with schizophrenia. Immunological parameters may help identify subgroups of individuals with signs of inflammation who well respond to anti-inflammatory therapy. Our integrative approach also identified gaps in knowledge about immune abnormalities in schizophrenia, and new horizons for the research are proposed.

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Section: Usefulness Of Immunological Data In Psychiatric Clinical Pra...mentioning

confidence: 99%

Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

et al. 2022

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“…A large number of investigations have reported biochemical alterations of the immune system in patients with schizophrenia (SZ), providing support of the immune/inflammatory hypothesis for SZ as a putative pathophysiological mechanism increasing the vulnerability to the illness [ 1 – 3 ]. Similarly, dysregulated immune/inflammatory responses and differential expression of immune-related genes have been observed in individuals with first-episode of psychosis (FEP) [ 4 – 7 ], indicating that immune aberrations may exist even at the early stages of psychosis, further corroborating the view that underlying immunological deficiencies could play a role in the development or progression of psychotic disorders [ 8 , 9 ]. In line with the above notion, genetic evidence has also emerged highlighting the involvement of genes coding for immune system components in SZ pathology [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 95%

Deregulation of complement components C4A and CSMD1 peripheral expression in first-episode psychosis and links to cognitive ability

Hatzimanolis

Foteli

Stefanatou

et al. 2022

Eur Arch Psychiatry Clin Neurosci

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Up-regulation of the complement component 4A (C4A) in the brain has been associated with excessive synaptic pruning and increased schizophrenia (SZ) susceptibility. Over-expression of C4A has been observed in SZ postmortem brain tissue, and the gene encoding for a protein inhibitor of C4A activity, CUB and Sushi multiple domains 1 (CSMD1) gene, has been implicated in SZ risk and cognitive ability. Herein, we examined C4A and CSMD1 mRNA expression in peripheral blood from antipsychotic-naive individuals with first-episode psychosis (FEP; n = 73) and mentally healthy volunteers (n = 48). Imputed C4 locus structural alleles and C4A serum protein levels were investigated. Associations with symptom severity and cognitive domains performance were explored. A significant decrease in CSMD1 expression levels was noted among FEP patients compared to healthy volunteers, further indicating a positive correlation between C4A and CSMD1 mRNA levels in healthy volunteers but not in FEP cases. In addition, C4 copy number variants previously associated with SZ risk correlated with higher C4A mRNA levels in FEP cases, which confirms the regulatory effect of C4 structural variants on gene expression. Evidence also emerged for markedly elevated C4A serum concentrations in FEP cases. Within the FEP patient group, higher C4A mRNA levels correlated with more severe general psychopathology symptoms and lower CSMD1 mRNA levels predicted worse working memory performance. Overall, these findings suggest C4A complement pathway perturbations in individuals with FEP and corroborate the involvement of CSMD1 in prefrontal-mediated cognitive functioning.

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“…Interestingly, three out of the four SMAD genes we detected as up‐regulated in schizophrenia, were found to be up‐regulated also in “Type 2”: SMAD4, SMAD5 and SMAD7 (Bowen et al, 2019). In addition, the literature suggests to classify schizophrenia into subtypes according to immunological and inflammatory features (Bishop et al, 2022; Enrico et al, 2021; Lin et al, 2016). Thus, the up‐regulation we detected might characterize only a subgroup of the patients.…”

Section: Discussionmentioning

confidence: 99%

SMAD genes are up‐regulated in brain and blood samples of individuals with schizophrenia

Wolf

Yitzhaky

Hertzberg

2023

J of Neuroscience Research

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Schizophrenia is a severe psychiatric disorder, with heritability around 80%, but a not fully understood pathophysiology. Signal transduction through the mothers against decapentaplegic (SMADs) are eight different proteins involved in the regulation of inflammatory processes, cell cycle, and tissue patterning. The literature is not consistent regarding the differential expression of SMAD genes among subjects with schizophrenia. In this article, we performed a systematic meta‐analysis of the expression of SMAD genes in 423 brain samples (211 schizophrenia vs. 212 healthy controls), integrating 10 datasets from two public repositories, following the PRISMA guidelines. We found a statistically significant up‐regulation of SMAD1, SMAD4, SMAD5, and SMAD7, and a tendency for up‐regulation of SMAD3 and SMAD9 in brain samples of patients with schizophrenia. Overall, six of the eight genes showed a tendency for up‐regulation, and none of them was found to have a tendency for down‐regulation. SMAD1 and SMAD4 were up‐regulated also in blood samples of 13 individuals with schizophrenia versus eight healthy controls, suggesting the SMAD genes' potential role as biomarkers of schizophrenia. Furthermore, SMAD genes' expression levels were significantly correlated with those of Sphingosine‐1‐phosphate receptor‐1 (S1PR1), which is known to regulate inflammatory processes. Our meta‐analysis supports the involvement of SMAD genes in the pathophysiology of schizophrenia through their role in inflammatory processes, as well as demonstrates the importance of gene expression meta‐analysis for improving our understanding of psychiatric diseases.

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Classification of Psychoses Based on Immunological Features: A Machine Learning Study in a Large Cohort of First-Episode and Chronic Patients

Cited by 13 publications

References 62 publications

Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

Deregulation of complement components C4A and CSMD1 peripheral expression in first-episode psychosis and links to cognitive ability

SMAD genes are up‐regulated in brain and blood samples of individuals with schizophrenia

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