| 1. |
- Just, David, et al.
(författare)
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Exploring autoantibody signatures in brain tissue from patients with severe mental illness
- 2020
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, studies have shown higher prevalence of autoantibodies in patients with schizophrenia compared to healthy individuals. This study applies an untargeted and a targeted affinity proteomics approach to explore and characterize the autoantibody repertoire in brain tissues from 73 subjects diagnosed with schizophrenia and 52 control subjects with no psychiatric or neurological disorders. Selected brain tissue lysates were first explored for IgG reactivity on planar microarrays composed of 11,520 protein fragments representing 10,820 unique proteins. Based on these results of ours and other previous studies of autoantibodies related to psychosis, we selected 226 fragments with an average length of 80 amino acids, representing 127 unique proteins. Tissue-based analysis of IgG reactivities using antigen suspension bead arrays was performed in a multiplex and parallel fashion for all 125 subjects. Among the detected autoantigens, higher IgG reactivity in subjects with schizophrenia, as compared to psychiatrically healthy subjects, was found against the glutamate ionotropic receptor NMDA type subunit 2D (anti-GluN2D). In a separate cohort with serum samples from 395 young adults with a wider spectrum of psychiatric disorders, higher levels of serum autoantibodies targeting GluN2D were found when compared to 102 control individuals. By further validating GluN2D and additional potential autoantigens, we will seek insights into how these are associated with severe mental illnesses.
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| 2. |
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| 3. |
- Lindholm Carlström, Eva, et al.
(författare)
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Transcriptome analysis of post-mortem brain tissue reveals up-regulation of the complement cascade in a subgroup of schizophrenia patients
- 2021
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Ingår i: Genes. - : MDPI. - 2073-4425. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a genetically complex neuropsychiatric disorder with largely unresolved mechanisms of pathology. Identification of genes and pathways associated with schizophrenia is important for understanding the development, progression and treatment of schizophrenia. In this study, pathways associated with schizophrenia were explored at the level of gene expression. The study included post-mortem brain tissue samples from 68 schizophrenia patients and 44 age and sex-matched control subjects. Whole transcriptome poly-A selected paired-end RNA sequencing was performed on tissue from the prefrontal cortex and orbitofrontal cortex. RNA expression differences were detected between case and control individuals, focusing both on single genes and pathways. The results were validated with RT-qPCR. Significant differential expression between patient and controls groups was found for 71 genes. Gene ontology analysis of differentially expressed genes revealed an up-regulation of multiple genes in immune response among the patients (corrected p-value = 0.004). Several genes in the category belong to the complement system, including C1R, C1S, C7, FCN3, SERPING1, C4A and CFI. The increased complement expression is primarily driven by a subgroup of patients with increased expression of immune/inflammatory response genes, pointing to important differences in disease etiology within the patient group. Weighted gene co-expression network analysis highlighted networks associated with both synaptic transmission and activation of the immune response. Our results demonstrate the importance of immune-related pathways in schizophrenia and provide evidence for elevated expression of the complement cascade as an important pathway in schizophrenia pathology.
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| 4. |
- Moghadam, Behrooz Torabi, et al.
(författare)
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Analyzing DNA methylation patterns in subjects diagnosed with schizophrenia using machine learning methods
- 2019
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Ingår i: Journal of Psychiatric Research. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0022-3956 .- 1879-1379. ; 114, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common mental disorder with high heritability. It is genetically complex and to date more than a hundred risk loci have been identified. Association of environmental factors and schizophrenia has also been reported, while epigenetic analyses have yielded ambiguous and sometimes conflicting results. Here, we analyzed fresh frozen post-mortem brain tissue from a cohort of 73 subjects diagnosed with schizophrenia and 52 control samples, using the Illumina Infinium HumanMethylation450 Bead Chip, to investigate genome-wide DNA methylation patterns in the two groups. Analysis of differential methylation was performed with the Bioconductor Minfi package and modern machine-learning and visualization techniques, which were shown previously to be successful in detecting and highlighting differentially methylated patterns in case-control studies. In this dataset, however, these methods did not uncover any significant signals discerning the patient group and healthy controls, suggesting that if there are methylation changes associated with schizophrenia, they are heterogeneous and complex with small effect.
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