Disclosing common biological signatures and predicting new therapeutic targets in schizophrenia and obsessive–compulsive disorder by integrated bioinformatics analysis

Abstract

Schizophrenia (SCZ) is a severe mental illness mainly characterized by a number of psychiatric symptoms. Obsessive–compulsive disorder (OCD) is a long-lasting and devastating mental disorder. SCZ has high co-occurrence with OCD resulting in the emergence of a concept entitled “schizo-obsessive disorder” as a new specific clinical entity with more severe psychiatric symptoms. Many studies have been done on SCZ and OCD, but the common pathogenesis between them is not clear yet. Therefore, this study aimed to identify shared genetic basis, potential biomarkers and therapeutic targets between these two disorders. Gene sets were extracted from the Geneweaver and Harmonizome databases for each disorder. Interestingly, the combination of both sets revealed 89 common genes between SCZ and OCD, the most important of which were BDNF, SLC6A4, GAD1, HTR2A, GRIN2B, DRD2, SLC6A3, COMT, TH and DLG4. Then, we conducted a comprehensive bioinformatics analysis of the common genes. Receptor activity as the molecular functions, neuron projection and synapse as the cellular components as well as serotonergic synapse, dopaminergic synapse and alcoholism as the pathways were the most significant commonalities in enrichment analyses. In addition, transcription factor (TFs) analysis predicted significant TFs such as HMGA1, MAPK14, HINFP and TEAD2. Hsa-miR-3121-3p and hsa-miR-495-3p were the most important microRNAs (miRNAs) associated with both disorders. Finally, our study predicted 19 existing drugs (importantly, Haloperidol, Fluoxetine and Melatonin) that may have a potential influence on this co-occurrence. To summarize, this study may help us to better understand and handle the co-occurrence of SCZ and OCD by identifying potential biomarkers and therapeutic targets.

Inhibition of autotaxin alleviates pathological features of hepatic encephalopathy at the level of gut–liver–brain axis: an experimental and bioinformatic study

“…To predict the microRNAs associated with each gene set and IL-1β, we used miRDB. All analyses were performed using the ToppFun section of ToppGene ( https://toppgene.cchmc.org/ ) with a cutoff value of P < 0.05 [ 40 ]. Finally, the results were presented in heat map charts and bar plots generated using GraphPad Prism software.…”

Potential biomarkers and therapeutic targets for obsessive compulsive disorder

“…As such, multiple studies have linked its dysregulated expression to different types of psychiatric disorders ( 22 ). For these reasons, BDNF may be demarcated as a potent biomarker involved in the pathology of psychiatric disorders such as schizophrenia and OCD ( 23 ). In particular, the Val-66-Met (rs6265) SNP, located in the terminal exon of the BDNF gene is an interesting candidate, and has often been found to be associated with the pathology of neuropsychiatric conditions such as OCD ( 24 ).…”

Establishing an OCD Model in BALB/c Mice Using RU24969: A Molecular and Behavioural Study of Optimal Dose Selection

“…Many studies provided strong evidence that the transmission of OCD is consistent with genetic transmission through specific brain chemical expression. These brain chemicals, such as serotonin, glutamate, and brain-derived neurotrophic factor, are involved in the severity of OCD symptoms [2][3][4][5]. Another factor, which is the environment, can affect the initiation and/or magnitude of OCD symptoms.…”