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Pro-/antiinflammatory dysregulation in early psychosis: results from a 1-year follow-up study.

García-Bueno B, Bioque M, MacDowell KS, Santabárbara J, Martínez-Cengotitabengoa M, Moreno C, Sáiz PA, Berrocoso E, Gassó P, Fe Barcones M, González-Pinto A, Parellada M, Bobes J, Micó JA, Bernardo M, Leza JC, FLAMM-PEPs study, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spa - Int. J. Neuropsychopharmacol. (2014)

Bottom Line: Multiple linear regression models were performed to detect the change of each biological marker during follow-up in relation to clinical characteristics and confounding factors.Summing up, pro-/antiinflammatory mediators can be used as risk/protection biomarkers.The inverse association between oxidative/nitrosative damage and the Global Assessment of Functioning scale, and the possibility that one of the targets of antipsychotics could be the restoration of the pro-/antiinflammatory balance support the use of antiinflammatory drugs as coadjuvant to antipsychotics.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, Complutense University, Instituto de Investigación Sanitaria -IIS- Hospital 12 de Octubre (i+12), Madrid, Spain (Drs García-Bueno, MacDowell, and Leza); Unitat d'Esquizofrènia Clínic, Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain (Drs Bioque and Bernardo); Department of Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, Spain (Dr Santabárbara); Hospital Universitario, Alava, EHU/UPV and National Distance Education University, Vitoria, Spain (Drs Martínez-Cengotitabengoa and González-Pinto); Child and Adolescent Psychiatry Department IIS Gregorio Marañón (IISGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain (Drs Moreno and Parellada); Department of Psychiatry, Faculty of Medicine, University of Oviedo, Oviedo, Spain (Drs Sáiz and Bobes); Department of Pharmacology, Faculty of Medicine, University of Cádiz, Cádiz, Spain (Drs Berrocoso and Micó); Department of Pharmacology, Faculty of Medicine, University of Barcelona, Barcelona, Spain (Dr Gassó); Hospital Clínico Universitario, Zaragoza, Spain (Dr Fe Barcones).

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Mean differences (SD) in proinflammatory biomarkers between first episode of psychosis (FEP) and controls (univariate analysis). (a) Nuclear transcription factor κB (NFκB) activity in peripheral blood mononuclear cell (PBMC) nuclear extracts from FEP patients (n = 85) and controls (n = 35). (b) Western-blot analysis of isoform 2 of cyclooxygenase (COX2) protein (patients n = 85, controls, n = 88); (c) Inducible nitric oxide synthase (iNOS) in PBMC cytosolic extracts from FEP patients (n = 85) and controls (n = 88); and (d) PGE2 (patients, n = 85; controls, n = 104). (e) Plasma levels of nitrites (NO−2) (patients, n = 85; controls, n = 61). (f) Thiobarbituric acid reactive substances (TBARS) (patients, n = 85; controls, n = 104). AU, arbitrary units. Two-tailed nonparametric Mann-Whitney U test was used. ° represents an atypical value and * an extreme value.
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Figure 1: Mean differences (SD) in proinflammatory biomarkers between first episode of psychosis (FEP) and controls (univariate analysis). (a) Nuclear transcription factor κB (NFκB) activity in peripheral blood mononuclear cell (PBMC) nuclear extracts from FEP patients (n = 85) and controls (n = 35). (b) Western-blot analysis of isoform 2 of cyclooxygenase (COX2) protein (patients n = 85, controls, n = 88); (c) Inducible nitric oxide synthase (iNOS) in PBMC cytosolic extracts from FEP patients (n = 85) and controls (n = 88); and (d) PGE2 (patients, n = 85; controls, n = 104). (e) Plasma levels of nitrites (NO−2) (patients, n = 85; controls, n = 61). (f) Thiobarbituric acid reactive substances (TBARS) (patients, n = 85; controls, n = 104). AU, arbitrary units. Two-tailed nonparametric Mann-Whitney U test was used. ° represents an atypical value and * an extreme value.

Mentions: Figure 1 shows mean differences (SD) in inflammatory and oxidative/nitrosative stress markers in control and FEP patients. NFκB is a master regulator of the inflammatory and oxidative/nitrosative status of a cell. In nuclear extracts from PMBCs, its activity is increased in FEP samples (supplementary Material 2 and Figure 1a). Similarly, COX2 expression was significantly higher in FEP subjects, although the expression of iNOS was not different between groups (supplementary Material 2 and Figure 1b-c). At this particular stage of the disease, the plasma levels of PGE2, NO−2, and TBARS were increased in FEP (supplementary Material 2 and Figure 1d-f, respectively). The numerical data for WB analysis from all subjects have been included in supplementary Table S3.


Pro-/antiinflammatory dysregulation in early psychosis: results from a 1-year follow-up study.

García-Bueno B, Bioque M, MacDowell KS, Santabárbara J, Martínez-Cengotitabengoa M, Moreno C, Sáiz PA, Berrocoso E, Gassó P, Fe Barcones M, González-Pinto A, Parellada M, Bobes J, Micó JA, Bernardo M, Leza JC, FLAMM-PEPs study, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spa - Int. J. Neuropsychopharmacol. (2014)

Mean differences (SD) in proinflammatory biomarkers between first episode of psychosis (FEP) and controls (univariate analysis). (a) Nuclear transcription factor κB (NFκB) activity in peripheral blood mononuclear cell (PBMC) nuclear extracts from FEP patients (n = 85) and controls (n = 35). (b) Western-blot analysis of isoform 2 of cyclooxygenase (COX2) protein (patients n = 85, controls, n = 88); (c) Inducible nitric oxide synthase (iNOS) in PBMC cytosolic extracts from FEP patients (n = 85) and controls (n = 88); and (d) PGE2 (patients, n = 85; controls, n = 104). (e) Plasma levels of nitrites (NO−2) (patients, n = 85; controls, n = 61). (f) Thiobarbituric acid reactive substances (TBARS) (patients, n = 85; controls, n = 104). AU, arbitrary units. Two-tailed nonparametric Mann-Whitney U test was used. ° represents an atypical value and * an extreme value.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368893&req=5

Figure 1: Mean differences (SD) in proinflammatory biomarkers between first episode of psychosis (FEP) and controls (univariate analysis). (a) Nuclear transcription factor κB (NFκB) activity in peripheral blood mononuclear cell (PBMC) nuclear extracts from FEP patients (n = 85) and controls (n = 35). (b) Western-blot analysis of isoform 2 of cyclooxygenase (COX2) protein (patients n = 85, controls, n = 88); (c) Inducible nitric oxide synthase (iNOS) in PBMC cytosolic extracts from FEP patients (n = 85) and controls (n = 88); and (d) PGE2 (patients, n = 85; controls, n = 104). (e) Plasma levels of nitrites (NO−2) (patients, n = 85; controls, n = 61). (f) Thiobarbituric acid reactive substances (TBARS) (patients, n = 85; controls, n = 104). AU, arbitrary units. Two-tailed nonparametric Mann-Whitney U test was used. ° represents an atypical value and * an extreme value.
Mentions: Figure 1 shows mean differences (SD) in inflammatory and oxidative/nitrosative stress markers in control and FEP patients. NFκB is a master regulator of the inflammatory and oxidative/nitrosative status of a cell. In nuclear extracts from PMBCs, its activity is increased in FEP samples (supplementary Material 2 and Figure 1a). Similarly, COX2 expression was significantly higher in FEP subjects, although the expression of iNOS was not different between groups (supplementary Material 2 and Figure 1b-c). At this particular stage of the disease, the plasma levels of PGE2, NO−2, and TBARS were increased in FEP (supplementary Material 2 and Figure 1d-f, respectively). The numerical data for WB analysis from all subjects have been included in supplementary Table S3.

Bottom Line: Multiple linear regression models were performed to detect the change of each biological marker during follow-up in relation to clinical characteristics and confounding factors.Summing up, pro-/antiinflammatory mediators can be used as risk/protection biomarkers.The inverse association between oxidative/nitrosative damage and the Global Assessment of Functioning scale, and the possibility that one of the targets of antipsychotics could be the restoration of the pro-/antiinflammatory balance support the use of antiinflammatory drugs as coadjuvant to antipsychotics.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, Complutense University, Instituto de Investigación Sanitaria -IIS- Hospital 12 de Octubre (i+12), Madrid, Spain (Drs García-Bueno, MacDowell, and Leza); Unitat d'Esquizofrènia Clínic, Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain (Drs Bioque and Bernardo); Department of Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, Spain (Dr Santabárbara); Hospital Universitario, Alava, EHU/UPV and National Distance Education University, Vitoria, Spain (Drs Martínez-Cengotitabengoa and González-Pinto); Child and Adolescent Psychiatry Department IIS Gregorio Marañón (IISGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain (Drs Moreno and Parellada); Department of Psychiatry, Faculty of Medicine, University of Oviedo, Oviedo, Spain (Drs Sáiz and Bobes); Department of Pharmacology, Faculty of Medicine, University of Cádiz, Cádiz, Spain (Drs Berrocoso and Micó); Department of Pharmacology, Faculty of Medicine, University of Barcelona, Barcelona, Spain (Dr Gassó); Hospital Clínico Universitario, Zaragoza, Spain (Dr Fe Barcones).

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Related in: MedlinePlus