Elevated Serum Purine Levels in Schizophrenia: A Reverse Translational Study to Identify Novel Inflammatory Biomarkers.
Biomarkers
P2X7 receptor
neuroinflammation
purinergic signaling
schizophrenia
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
16 08 2022
16 08 2022
Historique:
received:
09
12
2021
revised:
15
02
2022
accepted:
14
04
2022
pubmed:
21
4
2022
medline:
19
8
2022
entrez:
20
4
2022
Statut:
ppublish
Résumé
Immunological markers and related signaling molecules in the blood are altered in schizophrenia mouse models, in acutely relapsed patients with schizophrenia, and in persons at a clinically high risk for subsequently developing psychosis, highlighting their potential as prognostic and theranostic biomarkers. Therefore, we herein aimed to identify novel potential biomarkers in the serum that are associated with purinergic signaling. To our knowledge, this is the first study to assess the correlations among the levels of human serum adenine nucleotides (ATP, ADP), adenosine, P2X7 receptor, and disease activity in patients hospitalized due to an acute relapse of schizophrenia (n = 53) and healthy controls (n = 47). In addition, to validate these findings using a reverse translational approach, we examined the same parameters in an acute phencyclidine-induced schizophrenia mouse model. We found consistently elevated levels of ATP, ADP, interleukin (IL)-6, and IL-10 in both schizophrenia groups compared with the controls. The levels of adenosine, IL-1β, IL-12, and C-reactive protein were also increased in the human patient samples. Moreover, ATP and ADP were significantly positively correlated with the Positive and Negative Symptom Scale item "lack of judgment and insight"; IL-1β, IL-12, and tumour necrosis factor alpha were significantly positively correlated with "tension" and "depression"; and "disorientation" and "poor attention" were correlated significantly with IL-6 and IL-8. Our study suggests the promising potential of blood purines and inflammatory markers as future prognostic tools.
Sections du résumé
BACKGROUND
Immunological markers and related signaling molecules in the blood are altered in schizophrenia mouse models, in acutely relapsed patients with schizophrenia, and in persons at a clinically high risk for subsequently developing psychosis, highlighting their potential as prognostic and theranostic biomarkers. Therefore, we herein aimed to identify novel potential biomarkers in the serum that are associated with purinergic signaling.
METHODS
To our knowledge, this is the first study to assess the correlations among the levels of human serum adenine nucleotides (ATP, ADP), adenosine, P2X7 receptor, and disease activity in patients hospitalized due to an acute relapse of schizophrenia (n = 53) and healthy controls (n = 47). In addition, to validate these findings using a reverse translational approach, we examined the same parameters in an acute phencyclidine-induced schizophrenia mouse model.
RESULTS
We found consistently elevated levels of ATP, ADP, interleukin (IL)-6, and IL-10 in both schizophrenia groups compared with the controls. The levels of adenosine, IL-1β, IL-12, and C-reactive protein were also increased in the human patient samples. Moreover, ATP and ADP were significantly positively correlated with the Positive and Negative Symptom Scale item "lack of judgment and insight"; IL-1β, IL-12, and tumour necrosis factor alpha were significantly positively correlated with "tension" and "depression"; and "disorientation" and "poor attention" were correlated significantly with IL-6 and IL-8.
CONCLUSIONS
Our study suggests the promising potential of blood purines and inflammatory markers as future prognostic tools.
Identifiants
pubmed: 35443035
pii: 6571515
doi: 10.1093/ijnp/pyac026
pmc: PMC9380717
doi:
Substances chimiques
Biomarkers
0
Interleukin-1beta
0
Interleukin-6
0
Purines
0
Interleukin-12
187348-17-0
Adenosine Diphosphate
61D2G4IYVH
Adenosine Triphosphate
8L70Q75FXE
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
645-659Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.
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