Quantitative proteomic analysis of plasma in major mental disorders
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive Plus
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Dohyun Han
PROVIDER: MSV000098376 | MassIVE | Sun Jun 29 19:50:00 BST 2025
SECONDARY ACCESSION(S): PXD028841
REPOSITORIES: MassIVE
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Project description:Emerging high-throughput proteomic technologies have recently been considered as a powerful means of identifying substrates involved in mood disorders. We performed proteomic profiling using liquid chromatography-tandem mass spectrometry to identify dysregulated proteins in plasma samples of 44, 49, and 50 patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia , respectively, in comparison to 51 healthy controls (HCs).
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Project description:This dataset includes PRM-based plasma proteomics from adolescent patients diagnosed with Major Depressive Disorder (MDD), Bipolar Disorder (BD), and Schizophrenia (SZ), as well as healthy controls. The study aims to identify differentially expressed proteins and potential circulating biomarkers across psychiatric conditions, enabling evaluation of disease-specific molecular signatures and contributing to the understanding of adolescent psychiatric disorder pathophysiology.
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Project description:Genome wide association studies of schizophrenia encompassing the major histocompatibility locus (MHC) were highly significant following genome wide correction. This broad region implicates many genes including the MHC complex class II. Within this interval we examined the expression of two MHC II genes (HLA-DPA1 and HLA-DRB1) in brain from individual subjects with schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and controls by differential gene expression methods. A third MHC II mRNA, CD74, was studied outside of the MHC II locus, as it interacts within the same immune complex. HLA-DPA1 and CD74 were both reduced in hippocampus, amygdala, and dorsolateral prefrontal cortex regions in SZ and BD compared to controls by specific qPCR assay. We found several novel HLA-DPA1 mRNA variants spanning HLA-DPA1 exons 2-3-4 as suggested by an exon microarray study. The intronic rs9277341 SNP was a significant cis expression quantitative trait locus (eQTL) that was associated with the total expression of HLA-DPA1 in five brain regions. A biomarker study of MHC II mRNAs was conducted in SZ, BD, MDD, and control lymphoblastic cell lines (LCL) by qPCR assay of 87 subjects. There was significantly decreased expression of HLA-DPA1 and CD74 in BD, and trends for reductions in SZ in LCLs. The discovery of multiple splicing variants in brain for HLA-DPA1 is important as the HLA-DPA1 gene is highly conserved, there are no reported splicing variants, and the functions in brain are unknown. Future work on the function and localization of MHC Class II proteins in brain will help to understand the role of alterations in neuropsychiatric disorders. The HLA-DPA1 eQTL is located within a large linkage disequilibrium block that has an irrefutable association with schizophrenia. Future tests in a larger cohort are needed to determine the significance of this eQTL association with schizophrenia. Our findings support the long held hypothesis that alterations in immune function are associated with the pathophysiology of psychiatric disorders. There were 20 anterior cingulate postmortem brain samples that were extracted for total RNA, and analyzed using Affymetrix Exon Array (bipolar disorder subjects n = 9, controls n = 11).
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Project description:We conducted proteomic profiling of plasma, identifying both overlapping and unique differential proteins in adolescent patients diagnosed with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Our results showed that the protein signatures of adolescent psychiatric disorders differ significantly from those of adults. We propose potential targets for drug development aimed at the prevention or precision therapy of these psychiatric disorders. These findings enhance our understanding of the molecular etiology of adolescent psychiatric disorders. The specific biomolecular signatures of MDD, BD, and SZ could potentially serve as targets for the development of novel interventions aimed at prevention, early diagnosis, and treatment of these mental health conditions.
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Project description:Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions, with a lifetime prevalence of about 1%. Both disorders have a neurodevelopment component, with onset of symptoms occurring most frequently during late adolescence or early adulthood. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. These gene expression profiles were used to identify the molecular mechanisms that differentiate SZ and BP from healthy controls but also that distinguish both from healthy individuals. They were also used to expand an analysis from an experiment that searched molecular alterations in human induced pluripotent stem cells derived from fibroblasts from control subject and individual with schizophrenia and further differentiated to neuron to identify genes relevant for the development of schizophrenia (GSE62105). Brain tissue (frontal cortex) from 30 healthy controls, 29 bipolar disorder patients and 29 schizophrenia patients were analyzed. The reference is an in-house pool of RNA extracted from 15 human cell lines.
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Project description:Purpose of study is revealing significant differences in serum proteomes in schizophrenia, bipolar disorder (BD), and matched healthy controls. The sample preparation included affinity removing of six major proteins, separation by 1D electrophoresis, in-gel tryptic hydrolysis, and LC-MS/MS peptide analysis using LTQ Orbitrap Velos mass spectrometer. When comparing proteome profiles, different unique protein sets were revealed (absent in other groups): 22 proteins typical for schizophrenia, and 20 – for BD. Protein set in schizophrenia was mostly associated with nucleic acid and protein metabolism, immune response, cell communication, and cell growth and maintenance. Protein set in BD was mostly associated with cell growth and maintenance, nucleic acid metabolism regulation, immune response, protein metabolism, transport and cell communication. Concentrations of ankyrin repeat domain-containing protein 12 (ANKRD12), coagulation factor XIII, and cadherin 5 in serum samples were determined by ELISA. Significant difference between three groups was revealed in ANKRD12 concentration (p=0.02), with maximum elevation of ANKRD12 concentration (median level) in schizophrenia followed by BD. Cadherin 5 concentration differed significantly (p=0.035) between schizophrenic patients with prevailing positive symptoms (4.78 [2.71;7.12] ng/ml) and those with prevailing negative symptoms (1.86 [0.001;4.11] ng/ml). Our results are presumably useful for discovering the new pathways involved in endogenous psychotic disorders.
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Project description:Genome wide association studies of schizophrenia encompassing the major histocompatibility locus (MHC) were highly significant following genome wide correction. This broad region implicates many genes including the MHC complex class II. Within this interval we examined the expression of two MHC II genes (HLA-DPA1 and HLA-DRB1) in brain from individual subjects with schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and controls by differential gene expression methods. A third MHC II mRNA, CD74, was studied outside of the MHC II locus, as it interacts within the same immune complex. HLA-DPA1 and CD74 were both reduced in hippocampus, amygdala, and dorsolateral prefrontal cortex regions in SZ and BD compared to controls by specific qPCR assay. We found several novel HLA-DPA1 mRNA variants spanning HLA-DPA1 exons 2-3-4 as suggested by an exon microarray study. The intronic rs9277341 SNP was a significant cis expression quantitative trait locus (eQTL) that was associated with the total expression of HLA-DPA1 in five brain regions. A biomarker study of MHC II mRNAs was conducted in SZ, BD, MDD, and control lymphoblastic cell lines (LCL) by qPCR assay of 87 subjects. There was significantly decreased expression of HLA-DPA1 and CD74 in BD, and trends for reductions in SZ in LCLs. The discovery of multiple splicing variants in brain for HLA-DPA1 is important as the HLA-DPA1 gene is highly conserved, there are no reported splicing variants, and the functions in brain are unknown. Future work on the function and localization of MHC Class II proteins in brain will help to understand the role of alterations in neuropsychiatric disorders. The HLA-DPA1 eQTL is located within a large linkage disequilibrium block that has an irrefutable association with schizophrenia. Future tests in a larger cohort are needed to determine the significance of this eQTL association with schizophrenia. Our findings support the long held hypothesis that alterations in immune function are associated with the pathophysiology of psychiatric disorders.
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