iTRAQ-Based Serum Proteomic Analysis Reveals Multifactorial Cellular Function Impairment and Aggravated Systematic Inflammation in Drug-free Obsessive-Compulsive Disorders

Obsessive-compulsive disorder (OCD) is a debilitating
mental disorder
with obvious difficulties in treatment. Its pathogenesis has not been
fully elucidated. Further understanding of etiology and mechanism
needs to be explored further. We employed the isobaric tag for relative
and absolute quantitation (iTRAQ)-based proteomic analysis to compare
serum proteome profile between OCD patients and healthy controls,
in order to find out the possible mechanism of OCD in the downstream
biological process. Eighty-one drug-free OCD patients and 78 healthy
controls were enrolled. A total of 475 proteins were identified. Totally,
80 proteins with p < 0.05 were selected for gene
set enrichment analysis (GSEA), and only those with a fold change
≥1.2 and q value <0.2 between groups were
accepted as differentially expressed proteins (DEPs). We observed
a significant enrichment of immuno-inflammation-related pathways,
along with intriguing expression trends that immuno-inflammation-related
proteins were upregulated in GSEA. After that, 2 up-regulated proteins
and 13 down-regulated ones were accepted as DEP. According to the
available literature, most of the DEPs have not been reported in OCD.
These DEPs were enriched in 121 gene ontology (GO) terms, including
hepatocyte growth factor receptor activity, angiogenin-PRI complex,
and so on. DEPs were enriched in pathways including adherens junction
in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alterations
in DEPs including STXBP5L, GRN, and ANG were validated in OCD animal
models. Our study suggested that OCD patients manifested multifactorial
impairment in neuronal or non-neuronal cellular function under the
inflammatory background. Further research employing larger sample
sizes, longitudinal design, stratified analysis, and multiomics methodology
will be needed. Experiments in laboratories were essential in illuminating
the mechanism.