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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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.
© 2023 Elsevier Ltd
- Excitation/inhibition imbalance
- Gene expression
ASJC Scopus subject areas
- Psychiatry and Mental health
- Biological Psychiatry