PPARD May Play a Protective Role against the Development of Schizophrenia.

Xinrong Li,Yong Xu,Sha Liu,Karan Kapoor

doi:10.1155/2020/3480412

Abstract

PPARD has been suggested to contribute to the etiology of schizophrenia (SCZ) with the underlying mechanisms largely unknown. Here, we first collected and analyzed the PPARD expression profile from three groups: (1) 18 healthy control (HC) subjects, (2) 14 clinical high-risk (CHR) patients, and (3) 19 early onset of SCZ (EOS) patients. After that, we conducted a systematical pathway analysis to explore the potential mechanisms involved in PPARD exerting influence on the pathological development of SCZ. Compared to the HC group, the expression of PPARD was slightly decreased in the EOS group (LFC = −0.34; p = 0.23) and increased in the CHR group (LFC = 0.65; p = 0.20). However, there was a significant difference between the EOS group and the CHR group (LFC = −0.99; p = 0.015), reflecting the amount of variation in PPARD expression before and after the onset of SCZ. Pathway analysis suggested that overexpression of PPARD may regulate ten proteins or molecules to inhibit the pathological development of SCZ, including the deactivation of eight SCZ promoters and stimulation of two SCZ inhibitors. Our results support the association between PPARD and SCZ. The pathways identified may help in the understanding of the potential mechanisms by which PPARD contributes to the etiology of SCZ.

Highlights

Schizophrenia (SCZ) is a common and often disabling mental illness characterized by a varied group of clinical symptoms [1], but wide-ranging deficits in neurocognitive and neurophysiological functions [2, 3]
To explore the relationship between PPARD and SCZ, we studied the expression changes of PPARD in both clinical high-risk (CHR) and Early-onset SCZ (EOS) groups and compared that to the healthy control (HC) group
The changes were milder in terms of the statistical p value (p value = 0.23 and 0.20 for EOS vs HC and CHR vs HC, respectively)

Summary

Introduction

Schizophrenia (SCZ) is a common and often disabling mental illness characterized by a varied group of clinical symptoms [1], but wide-ranging deficits in neurocognitive and neurophysiological functions [2, 3]. The prodromal period is thought to have a high risk of clinical symptoms and precedes illness onset by 1 to 6 years [4, 5]. Subjects with these characteristics are called clinical high-risk (CHR) patients, with about one-third developing SCZ and twothird recovering to normal [4, 5] (PMID: 8782291; PMID: 1571314). PPARD is a nuclear hormone receptor that governs a variety of biological processes [9] This gene has been suggested to play roles in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer [10]. The underlying mechanism regarding the PPARD-SCZ association is largely unknown

Methods

Results

Conclusion