Alteration in the mRNA expression profile of the autophagy-related mTOR pathway in schizophrenia patients treated with olanzapine.
Autophagy
Autophagy-Related Proteins
Humans
Intracellular Signaling Peptides and Proteins
Olanzapine
/ therapeutic use
RNA, Messenger
/ genetics
Rapamycin-Insensitive Companion of mTOR Protein
Regulatory-Associated Protein of mTOR
Schizophrenia
/ drug therapy
Sirolimus
TOR Serine-Threonine Kinases
/ genetics
DEPTOR
Olanzapine
Schizophrenia
mRNA expression
mTOR pathway
Journal
BMC psychiatry
ISSN: 1471-244X
Titre abrégé: BMC Psychiatry
Pays: England
ID NLM: 100968559
Informations de publication
Date de publication:
04 08 2021
04 08 2021
Historique:
received:
18
01
2021
accepted:
26
07
2021
entrez:
5
8
2021
pubmed:
6
8
2021
medline:
10
8
2021
Statut:
epublish
Résumé
The mammalian target of rapamycin protein (mTOR) signaling pathway is involved in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions to antipsychotic drugs, which might be mediated by an mTOR-dependent autophagy impairment. This study aimed to examine the expression of mTOR pathway genes in patients with schizophrenia treated with olanzapine, which is considered an mTOR inhibitor and autophagy inducer. Thirty-two patients with acute schizophrenia who had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d) and 32 healthy volunteers were recruited. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of patients with schizophrenia, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RAPTOR, and DEPTOR, were detected in fasting venous blood samples from all subjects using real-time quantitative PCR. The MTOR and RICTOR mRNA expression levels in patients with acute schizophrenia were significantly decreased compared with those of healthy controls and further significantly decreased after four weeks of olanzapine treatment. The DEPTOR mRNA expression levels in patients with acute schizophrenia were not significantly different from those of healthy controls but were significantly increased after treatment. The expression levels of the RAPTOR mRNA were not significantly different among the three groups. The pairwise correlations of MTOR, DEPTOR, RAPTOR, and RICTOR mRNA expression levels in patients with acute schizophrenia and healthy controls were significant. After olanzapine treatment, the correlations between the expression levels of the DEPTOR and MTOR mRNAs and between the DEPTOR and RICTOR mRNAs disappeared. Abnormalities in the mTOR pathway, especially DEPTOR and mTORC2, might play important roles in the autophagy mechanism underlying the pathophysiology of schizophrenia and effects of olanzapine treatment.
Sections du résumé
BACKGROUND
The mammalian target of rapamycin protein (mTOR) signaling pathway is involved in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions to antipsychotic drugs, which might be mediated by an mTOR-dependent autophagy impairment. This study aimed to examine the expression of mTOR pathway genes in patients with schizophrenia treated with olanzapine, which is considered an mTOR inhibitor and autophagy inducer.
METHODS
Thirty-two patients with acute schizophrenia who had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d) and 32 healthy volunteers were recruited. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of patients with schizophrenia, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RAPTOR, and DEPTOR, were detected in fasting venous blood samples from all subjects using real-time quantitative PCR.
RESULTS
The MTOR and RICTOR mRNA expression levels in patients with acute schizophrenia were significantly decreased compared with those of healthy controls and further significantly decreased after four weeks of olanzapine treatment. The DEPTOR mRNA expression levels in patients with acute schizophrenia were not significantly different from those of healthy controls but were significantly increased after treatment. The expression levels of the RAPTOR mRNA were not significantly different among the three groups. The pairwise correlations of MTOR, DEPTOR, RAPTOR, and RICTOR mRNA expression levels in patients with acute schizophrenia and healthy controls were significant. After olanzapine treatment, the correlations between the expression levels of the DEPTOR and MTOR mRNAs and between the DEPTOR and RICTOR mRNAs disappeared.
CONCLUSIONS
Abnormalities in the mTOR pathway, especially DEPTOR and mTORC2, might play important roles in the autophagy mechanism underlying the pathophysiology of schizophrenia and effects of olanzapine treatment.
Identifiants
pubmed: 34348681
doi: 10.1186/s12888-021-03394-w
pii: 10.1186/s12888-021-03394-w
pmc: PMC8335969
doi:
Substances chimiques
Autophagy-Related Proteins
0
Intracellular Signaling Peptides and Proteins
0
RICTOR protein, human
0
RNA, Messenger
0
RPTOR protein, human
0
Rapamycin-Insensitive Companion of mTOR Protein
0
Regulatory-Associated Protein of mTOR
0
DEPTOR protein, human
EC 2.7.1.1
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Olanzapine
N7U69T4SZR
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
388Subventions
Organisme : Medical Young Talents Programme in the Provincial Science and Education of Health Project of the Jiangsu Provincial Health Commission
ID : QNRC2016176
Organisme : General Programof the Jiangsu Provincial Health Commission
ID : Z2017014
Organisme : Top Talent Support Program for young and middle-aged people of the Wuxi Health Committee
ID : BJ2020084
Organisme : General Program of the Wuxi Health Committee
ID : M202013
Informations de copyright
© 2021. The Author(s).
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