Comprehensive Gene Expression Analysis Detects Global Reduction of Proteasome Subunits in Schizophrenia.
Schizophr Bull
; 47(3): 785-795, 2021 04 29.
Article
en En
| MEDLINE
| ID: mdl-33141894
ABSTRACT
BACKGROUND:
The main challenge in the study of schizophrenia is its high heterogeneity. While it is generally accepted that there exist several biological mechanisms that may define distinct schizophrenia subtypes, they have not been identified yet. We performed comprehensive gene expression analysis to search for molecular signals that differentiate schizophrenia patients from healthy controls and examined whether an identified signal was concentrated in a subgroup of the patients.METHODS:
Transcriptome sequencing of 14 superior temporal gyrus (STG) samples of subjects with schizophrenia and 15 matched controls from the Stanley Medical Research Institute (SMRI) was performed. Differential expression and pathway enrichment analysis results were compared to an independent cohort. Replicability was tested on 6 additional independent datasets.RESULTS:
The 2 STG cohorts showed high replicability. Pathway enrichment analysis of the down-regulated genes pointed to proteasome-related pathways. Meta-analysis of differential expression identified down-regulation of 12 of 39 proteasome subunit genes in schizophrenia. The signal of proteasome subunits down-regulation was replicated in 6 additional datasets (overall 8 cohorts with 267 schizophrenia and 266 control samples, from 5 brain regions). The signal was concentrated in a subgroup of patients with schizophrenia.CONCLUSIONS:
We detected global down-regulation of proteasome subunits in a subgroup of patients with schizophrenia. We hypothesize that the down-regulation of proteasome subunits leads to proteasome dysfunction that causes accumulation of ubiquitinated proteins, which has been recently detected in a subgroup of schizophrenia patients. Thus, down-regulation of proteasome subunits might define a biological subtype of schizophrenia.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Esquizofrenia
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Encéfalo
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Perfilación de la Expresión Génica
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Complejo de la Endopetidasa Proteasomal
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Transcriptoma
Tipo de estudio:
Diagnostic_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Schizophr Bull
Año:
2021
Tipo del documento:
Article
País de afiliación:
Israel