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. 2019 Jul-Sep;9(3):286-293.
doi: 10.1016/j.jobcr.2019.06.009. Epub 2019 Jun 15.

Salivary Flow Alteration in Patients Undergoing Treatment for Schizophrenia: Disease-Drug-Target Gene/Protein Association Study for Side-effects

Anusa Arunachalam Mohandoss  1 , Rooban Thavarajah  2
Affiliations

Salivary Flow Alteration in Patients Undergoing Treatment for Schizophrenia: Disease-Drug-Target Gene/Protein Association Study for Side-effects

Anusa Arunachalam Mohandoss et al. J Oral Biol Craniofac Res. 2019 Jul-Sep.

Abstract

Background: Salivary flow alteration (SA), is a known unwarranted effect of schizophrenic medications. It manifest either as reduced (xerostomia) or increased (sialorrhea) SA, among treated schizophrenic patients. It is believed that the SA is due to action of the drugs/disease process involving the muscarinic receptor-3 to process acetyl choline, the common neurotransmitter. The genetic mediation behind the SA in such patients remains largely unexplored. We aimed to address the same by using curated literary databases to identify such relationship, if any existed.

Material and methods: Curated databases of Gene-Disease Association, www.DisGeNet.org and www.networkanalyst.ca were effectively used to identify the probable genes, strength of association and the drug-genes pathway that could be possibly be involved. The genes associated with schizophrenia and SA were analyzed in detail. Protein-Protein interaction (PPI) network proven experimentally in humans were used to identify the missing or unreported links.

Results: In all 28 genes associated with schizophrenia were linked to SA. The genetic network of schizophrenia and xerostomia involved FGFR2 gene prominently and network module was statistically significant (P = 9.87*10-8) was achieved that had xerostomia as a node, while schizophrenia (P = 0.025) had statistical significance. Sialorrhea had no statistical significance (P = 0.555). When schizophrenia and sialorrhea connections were analyzed for genetic interaction, only gene GCH1 emerged. On combining the three disease entities, the association of TAC1 gene with sialorrhea was also identified. Using PPI, the coordination of CHRM3, TAC1 and GPRASP1 gene were identified. This network involved several genes that has significant influence on calcium signaling pathway (P = 7.74*10-16), cholingeric synapse(P = 6 × 10-4), salivary secretion(P = 4.38*10-3), endocytosis(P = 8.23*10-4), TGFβ signaling pathway(P = 0.0031), gap junction (P = 4.08*10-3) and glutamergic synapse(P = 6.4*10-3). The involvement of G-receptor signaling protein product, GNAQ was established.

Discussion and conclusion: The possible genetic pathway of SA in schizophrenic patients are discussed in light of pharmacotherapeutics. Using the knowledge effectively would help to increase the quality of life of schizophrenic besides increasing the understanding to use saliva as a biomarker of prognosis of schizophrenia and its drug effects.

Keywords: Antipsychotic drugs; Genes; Protein-protein interaction; Schizophrenia; Sialorrhea; Xerostomia.

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Figures

Fig. 1
Fig. 1
Schizophrenia-Salivary Flow Alternation Genes-Disease Association network, Blue - Strong nodes from seed, Red - Identified nodes.
Fig. 2
Fig. 2
Close look of the Schizophrenia, Xerostomia and Sialorrhea from figure- 1 network.
Fig. 3
Fig. 3
Modules in the network. For color legend see text.
Fig. 4
Fig. 4
Focused network of the salivary alteration and schizophrenia related genes.
Fig. 5
Fig. 5
Genes and Drugs interaction.
Fig. 6
Fig. 6
Pathway analysis of Salivary flow alteration and Schizophrenia related genes.
See this image and copyright information in PMC

References

    1. Nascimento J.M., Martins-de-Souza D. The proteome of schizophrenia. NPJ Schizophr. 2015;1 Article number 14003. - PMC - PubMed
    1. Hattori S., Suda A., Kishida I. Association between dysfunction of autonomic nervous system activity and mortality in schizophrenia. Compr Psychiatr. 2018;86:19–22. - PubMed
    1. Essali A., Rihawi A., Altujjar M., Alhafez B., Tarboush A., Alhaj Hasan N. Anticholinergic medication for non-clozapine neuroleptic-induced hypersalivation in people with schizophrenia. Cochrane Database Syst Rev. 2013:CD009546. - PMC - PubMed
    1. Salzmann-Erikson M., Sjodin M. A narrative meta-synthesis of how people with schizophrenia experience facilitators and barriers in using antipsychotic medication: implications for healthcare professionals. Int J Nurs Stud. 2018;85:7–18. - PubMed
    1. Maher S., Cunningham A., O'Callaghan N. Clozapine-induced hypersalivation: an estimate of prevalence, severity and impact on quality of life. Ther Adv Psychopharmacol. 2016;6:178–184. - PMC - PubMed