Ribosome subunits are upregulated in brain samples of a subgroup of individuals with schizophrenia: A systematic gene expression meta-analysis

Ori Mekiten; Assif Yitzhaky; Nathaniel Gould; Kobi Rosenblum; Libi Hertzberg

doi:10.1016/j.jpsychires.2023.06.013

Ribosome subunits are upregulated in brain samples of a subgroup of individuals with schizophrenia: A systematic gene expression meta-analysis

Ori Mekiten, Assif Yitzhaky, Nathaniel Gould, Kobi Rosenblum, Libi Hertzberg

Department of Neurobiology

Research output: Contribution to journal › Article › peer-review

Abstract

One of the new theories accounting for the underlying pathophysiology of schizophrenia is excitation/inhibition imbalance. Interestingly, perturbation in protein synthesis machinery as well as oxidative stress can lead to excitation/inhibition imbalance. We thus performed a systematic meta-analysis of the expression of 79 ribosome subunit genes and two oxidative-stress related genes, HIF1A and NQO1, in brain samples of individuals with schizophrenia vs. healthy controls. We integrated 12 gene expression datasets, following the PRISMA guidelines (overall 511 samples, 253 schizophrenia and 258 controls). Five ribosome subunit genes were significantly upregulated in a subgroup of the patients with schizophrenia, while 24 (30%) showed a tendency for upregulation. HIF1A and NQO1 were also found to be significantly upregulated. Moreover, HIF1A and NQO1 showed positive correlation with the expression of the upregulated ribosome subunit genes. Our results, together with previous findings, suggest a possible role for altered mRNA translation in the pathogenesis of schizophrenia, in association with markers of increased oxidative stress in a subgroup of patients. Further studies should define whether the upregulation of ribosome subunits result in altered mRNA translation, which proteins are modulated and how it characterizes a subgroup of the patients with schizophrenia.

Original language	English
Pages (from-to)	372-381
Number of pages	10
Journal	Journal of Psychiatric Research
Volume	164
DOIs	https://doi.org/10.1016/j.jpsychires.2023.06.013
State	Published - Aug 2023

Bibliographical note

Funding Information:
To further validate our results, Pearson correlation coefficients were calculated between each pair of RPL and RPS genes, in each of the 12 datasets separately. RPL18 and RPL24 show significant positive correlation in each of the 12 datasets (Fig. 3; combined data Corr = 0.63, p-value = 7*10−24). Similarly, most of the RPL and RPS genes were positively correlated with each other in each of the datasets included in our meta-analysis (Fig. 4S). Overall, the significant positive correlation coefficient values between the expression patterns of the RPL and RPS genes support the results of our meta-analysis and reduce the likelihood of false positives caused by arbitrary noise.

Publisher Copyright:
© 2023 Elsevier Ltd

Keywords

Excitation/inhibition imbalance
Gene expression
Oxidative-stress
RPL
RPS
Schizophrenia

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jpsychires.2023.06.013

Cite this

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title = "Ribosome subunits are upregulated in brain samples of a subgroup of individuals with schizophrenia: A systematic gene expression meta-analysis",

abstract = "One of the new theories accounting for the underlying pathophysiology of schizophrenia is excitation/inhibition imbalance. Interestingly, perturbation in protein synthesis machinery as well as oxidative stress can lead to excitation/inhibition imbalance. We thus performed a systematic meta-analysis of the expression of 79 ribosome subunit genes and two oxidative-stress related genes, HIF1A and NQO1, in brain samples of individuals with schizophrenia vs. healthy controls. We integrated 12 gene expression datasets, following the PRISMA guidelines (overall 511 samples, 253 schizophrenia and 258 controls). Five ribosome subunit genes were significantly upregulated in a subgroup of the patients with schizophrenia, while 24 (30%) showed a tendency for upregulation. HIF1A and NQO1 were also found to be significantly upregulated. Moreover, HIF1A and NQO1 showed positive correlation with the expression of the upregulated ribosome subunit genes. Our results, together with previous findings, suggest a possible role for altered mRNA translation in the pathogenesis of schizophrenia, in association with markers of increased oxidative stress in a subgroup of patients. Further studies should define whether the upregulation of ribosome subunits result in altered mRNA translation, which proteins are modulated and how it characterizes a subgroup of the patients with schizophrenia.",

keywords = "Excitation/inhibition imbalance, Gene expression, Oxidative-stress, RPL, RPS, Schizophrenia",

author = "Ori Mekiten and Assif Yitzhaky and Nathaniel Gould and Kobi Rosenblum and Libi Hertzberg",

note = "Funding Information: To further validate our results, Pearson correlation coefficients were calculated between each pair of RPL and RPS genes, in each of the 12 datasets separately. RPL18 and RPL24 show significant positive correlation in each of the 12 datasets (Fig. 3; combined data Corr = 0.63, p-value = 7*10−24). Similarly, most of the RPL and RPS genes were positively correlated with each other in each of the datasets included in our meta-analysis (Fig. 4S). Overall, the significant positive correlation coefficient values between the expression patterns of the RPL and RPS genes support the results of our meta-analysis and reduce the likelihood of false positives caused by arbitrary noise. Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",

year = "2023",

month = aug,

doi = "10.1016/j.jpsychires.2023.06.013",

language = "English",

volume = "164",

pages = "372--381",

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AU - Mekiten, Ori

AU - Yitzhaky, Assif

AU - Gould, Nathaniel

AU - Rosenblum, Kobi

AU - Hertzberg, Libi

N1 - Funding Information: To further validate our results, Pearson correlation coefficients were calculated between each pair of RPL and RPS genes, in each of the 12 datasets separately. RPL18 and RPL24 show significant positive correlation in each of the 12 datasets (Fig. 3; combined data Corr = 0.63, p-value = 7*10−24). Similarly, most of the RPL and RPS genes were positively correlated with each other in each of the datasets included in our meta-analysis (Fig. 4S). Overall, the significant positive correlation coefficient values between the expression patterns of the RPL and RPS genes support the results of our meta-analysis and reduce the likelihood of false positives caused by arbitrary noise. Publisher Copyright: © 2023 Elsevier Ltd

PY - 2023/8

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N2 - One of the new theories accounting for the underlying pathophysiology of schizophrenia is excitation/inhibition imbalance. Interestingly, perturbation in protein synthesis machinery as well as oxidative stress can lead to excitation/inhibition imbalance. We thus performed a systematic meta-analysis of the expression of 79 ribosome subunit genes and two oxidative-stress related genes, HIF1A and NQO1, in brain samples of individuals with schizophrenia vs. healthy controls. We integrated 12 gene expression datasets, following the PRISMA guidelines (overall 511 samples, 253 schizophrenia and 258 controls). Five ribosome subunit genes were significantly upregulated in a subgroup of the patients with schizophrenia, while 24 (30%) showed a tendency for upregulation. HIF1A and NQO1 were also found to be significantly upregulated. Moreover, HIF1A and NQO1 showed positive correlation with the expression of the upregulated ribosome subunit genes. Our results, together with previous findings, suggest a possible role for altered mRNA translation in the pathogenesis of schizophrenia, in association with markers of increased oxidative stress in a subgroup of patients. Further studies should define whether the upregulation of ribosome subunits result in altered mRNA translation, which proteins are modulated and how it characterizes a subgroup of the patients with schizophrenia.

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ER -

Ribosome subunits are upregulated in brain samples of a subgroup of individuals with schizophrenia: A systematic gene expression meta-analysis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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