Serum proteomics in schizophrenia
Ontology highlight
ABSTRACT:
INSTRUMENT(S): none
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
DongDong Qi
PROVIDER: MSV000095241 | MassIVE | Wed Jul 03 23:13:00 BST 2024
SECONDARY ACCESSION(S): PXD053629
REPOSITORIES: MassIVE
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Project description:Schizophrenia is best considered a “two-hit” disease, with a neurodevelopment impairment followed by an additional process in early adulthood. Both are regulated by hormonal (like thyroid and retinols) and signal transduction pathways (like WNT), which in turn have been previously identified in post-mortem brain studies of schizophrenic individuals. While brain studies are fitted for pathology assessment, there are not suitable for searches of a “diagnostic signature” of schizophrenia. In contrast, peripheral blood is easily accessible, and can be used for the study of disease pathways and potentially diagnosis markers. Blood from twenty eight males with DSM-IV schizophrenia under three drug regimens (clozapine, risperidone or haloperidol), and from 10 healthy controls was studied in a microarray platform with 1364 genes belonging to hormonal and signal transduction pathways. Seven genes were differentially expressed between controls and patients with different treatments, and 28 between healthy controls and specific treatments, with four (CTNNA1, GSTM3, HOXA-13 and KRT18) altered in all analyses. While none of these genes has been previously reported in schizophrenia brain studies, many belong to pathways altered in schizophrenia, belonging to chromosomal loci linked to the disease, which warrants additional replication studies to be performed in larger samples.
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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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