Identification of Common Pathogenetic Processes between Schizophrenia and Diabetes Mellitus by Systems Biology Analysis.

Md Rezanur Rahman,Bashair M Mussa,Esra Gov,Md Rafiqul Islam,Paolo Fagone,Mohammad Ali Moni,Manuela Pennisi,Tania Islam,Alessia Bramanti,Ferdinando Nicoletti,Maria Cristina Petralia,Rosella Ciurleo,Talip Yasir Demirtas,Francesco Fisicaro

doi:10.3390/genes12020237

Abstract

Schizophrenia (SCZ) is a psychiatric disorder characterized by both positive symptoms (i.e., psychosis) and negative symptoms (such as apathy, anhedonia, and poverty of speech). Epidemiological data show a high likelihood of early onset of type 2 diabetes mellitus (T2DM) in SCZ patients. However, the molecular processes that could explain the epidemiological association between SCZ and T2DM have not yet been characterized. Therefore, in the present study, we aimed to identify underlying common molecular pathogenetic processes and pathways between SCZ and T2DM. To this aim, we analyzed peripheral blood mononuclear cell (PBMC) transcriptomic data from SCZ and T2DM patients, and we detected 28 differentially expressed genes (DEGs) commonly modulated between SCZ and T2DM. Inflammatory-associated processes and membrane trafficking pathways as common biological processes were found to be in common between SCZ and T2DM. Analysis of the putative transcription factors involved in the regulation of the DEGs revealed that STAT1 (Signal Transducer and Activator of Transcription 1), RELA (v-rel reticuloendotheliosis viral oncogene homolog A (avian)), NFKB1 (Nuclear Factor Kappa B Subunit 1), and ERG (ETS-related gene) are involved in the expression of common DEGs in SCZ and T2DM. In conclusion, we provide core molecular signatures and pathways that are shared between SCZ and T2DM, which may contribute to the epidemiological association between them.

Highlights

Schizophrenia (SCZ) is a psychiatric disorder characterized by psychotic events in a continuous and/or relapsing mode
We performed a transcriptomic meta-analysis of two SCZ peripheral blood mononuclear cell (PBMC) datasets obtained from the Gene Expression Omnibus (GEO) database
This study aimed to provide novel molecular signatures and pathways that may underlie both SCZ and type 2 diabetes mellitus (T2DM) pathogenesis

Summary

Introduction

Schizophrenia (SCZ) is a psychiatric disorder characterized by psychotic events in a continuous and/or relapsing mode. Compared to the general population, SCZ patients are reported with a 1.5–2 times higher risk of type 2 diabetes (T2DM) [1]. People with serious psychiatric disorders live sedentary lives and smoke more often than the general population, which are considered as risk factors of T2DM [4]. Multiple reports have demonstrated a link between antipsychotic medications and the likelihood of developing T2DM [6,7,8], but this still needs further confirmation [4]. Multiple etiopathogenetic mechanisms seem to be involved in the association between SCZ and T2DM. Genetic predispositions are recognized, it is believed that environmental, neurological, and metabolic processes may contribute to the increased risk of developing T2DM by SCZ patients. The pathogenetic mechanisms of nongenetic variants of SCZ and T2DM still need to be explored

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