15-deoxyprostaglandin-j2 and Schizophrenia

Many hypotheses have been proposed for the development of schizophrenia, including the one proposing that exogenous and endogenous factors are linked to inflammatory processes. There is strong evidence about the immunological and inflammatory dysfunction in schizophrenia. In this study, we aimed to measure serum 15-deoxy-delta(12,14)-prostaglandin J (15d-PGJ), peroxisome proliferator-activated receptor gamma(PPARγ), prostaglandin E2 (PGE2) and C-reactive protein (CRP) levels. Forty-four patients and 39 healthy volunteers were included in the study. Serum PGE2, 15d-PGJ, PPARγ and CRP levels were measured in both the groups. Demographic data forms were filled out for the patient group, and the Positive and Negative Syndrome Scale, Clinical Global Impression-Severity scale and Calgary Depression scale were used to assess patients' clinical status. Serum PGE2, 15d-PGJ and PPARγ levels were found to be significantly lower in patients with schizophrenia than in healthy controls. There was no significant relationship between the serum PGE2, 15d-PGJ and PPARγ levels and CRP levels.In this study, the evidence of systemic inflammatory conditions in patients with schizophrenia was found. The duration of the disease has been found to be the only variable that independently affects all three biomarker levels in the patients with schizophrenia.

Topics: Adult; Biomarkers; C-Reactive Protein; Dinoprostone; Female; Humans; Inflammation; Male; Middle Aged; PPAR gamma; Prostaglandin D2; Schizophrenia

Immune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear.. To identify potential differential intra-/intercellular biochemical pathways controlling immune-inflammatory response and their oxidative-nitrosative impact on SCH patients, compared with bipolar disorder (BD) patients and healthy controls (HC).. Cross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)].. ANCOVA (or Quade test) controlling for age and gender when comparing the three groups, and controlling for age, gender, length of illness, cigarettes per day, and body mass index (BMI) when comparing SCH and BD.. Pro-inflammatory biomarkers: Expression of COX-1 was statistically higher in SCH and BD than HC (P<0.0001; P<0.0001); NFκB and PGE2 were statistically higher in SCH compared with BD (P=0.001; P<0.0001) and HC (P=0.003; P<0.0001); NLRP3 was higher in BD than HC (P=0.005); and CPR showed a gradient among the three groups. Anti-inflammatory biomarkers: BD patients had lower PPARγ and higher 15d-PGJ2 levels than SCH (P=0.005; P=0.008) and HC (P=0.001; P=0.001). Differences between SCH and BD: previous markers of SCH (NFκB and PGE2) and BD (PPARγ and 15d-PGJ2) remained statistically significant and, interestingly, iNOS and COX-2 (pro-inflammatory biomarkers) levels were statistically higher in SCH than BD (P=0.019; P=0.040).. This study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.

Topics: Adult; Biomarkers; Bipolar Disorder; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Inflammation; Male; Middle Aged; PPAR gamma; Prostaglandin D2; Schizophrenia; Schizophrenic Psychology; Young Adult

Schizophrenia is a chronic syndrome of unknown etiology, predominantly defined by signs of psychosis. The onset of the disorder occurs typically in late adolescence or early adulthood. Efforts to study pathophysiological mechanisms in early stages of the disease are crucial in order to prompt intervention.. Case-control study of first-episode psychotic (FEP) patients and matched controls. We recruited 117 patients during the first year after their FEP according to the DSM-IV criteria and recruited 106 gender-, race-, and age-matched controls between September 2010 and June 2011.. Biochemical studies carried out in peripheral mononuclear blood cells (PMBC) and plasma evidence a significant increase in intracellular components of a main proinflammatory pathway, along with a significant decrease in the anti-inflammatory ones. Multivariate logistic regression analyses identified the expression of inducible isoforms of nitric oxide synthase and cyclooxygenase in PMBC and homocysteine plasma levels as the most reliable potential risk factors and the inhibitor of the inflammatory transcription factor NFκB, IκBα, and the anti-inflammatory prostaglandin 15d-PGJ2 as potential protection factors.. Taken as a whole, the results of this study indicate robust phenotypical differences at the cellular machinery level in PMBC of patients with FEP. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways including the activity of nuclear receptors has interesting potential as biological markers and potential risk/protective factors for FEP. Due to its soluble nature, a notable finding in this study is that the anti-inflammatory mediator 15d-PGJ2 might be used as plasmatic biomarker for first episodes of psychosis.

Topics: Adolescent; Adult; Biomarkers; Case-Control Studies; Female; Humans; Immunity, Cellular; Inflammation; Male; Phenotype; Prostaglandin D2; Psychotic Disorders; Risk Factors; Schizophrenia; Time Factors; Young Adult

A number of findings suggest that inflammation plays a role in the pathophysiology of schizophrenia. Taking into account a physiological balance between pro- and anti-inflammatory mediators, we measured the plasma levels of cyclooxygenase-derived mediators and other key pro- and anti-inflammatory transcription factors in peripheral blood mononuclear cells (PBMC). Forty healthy subjects and 46 treated chronic schizophrenic patients with an acutely exacerbated condition who met DSM-IV criteria were included. COX by-products prostaglandin E2 (PGE2) and 15d-prostaglandin J2 (15d-PGJ2) plasma levels were measured by EIA. Peroxisome proliferator-activated receptor gamma (PPARγ) as well as nuclear factor kappaB (NFκB) activity in nuclear extracts from PBMC and expression of its inhibitory subunit IκBα in cytosolic extracts were determined using ELISA-based kits. Schizophrenic patients showed higher plasma levels of pro-inflammatory PGE2 than age-matched controls (p=0.043). On the contrary, levels of anti-inflammatory 15-d-PGJ2 were lower (p=0.004), correlating with a lower expression of its nuclear target, PPARγ in nuclear extracts from PBMC (p=0.001). Although no changes in NFκB activity were observed between patients and healthy controls, the expression of its inhibitory protein IκBα was lower in the patients compared to the controls (p=0.027). These findings suggest that schizophrenia is associated with a systemic imbalance in the plasma levels of pro-inflammatory/anti-inflammatory prostaglandins in favor of the former. Furthermore, the expression and activity of anti-inflammatory PPARγ are diminished in PBMC, which indicates a state of inflammation and blunted anti-inflammatory counterbalancing mechanisms at systemic level in these patients.

Topics: Adolescent; Adult; Dinoprostone; Female; Humans; Immunoenzyme Techniques; Leukocytes, Mononuclear; Male; Middle Aged; NF-kappa B; PPAR gamma; Prostaglandin D2; Psychiatric Status Rating Scales; Schizophrenia; Young Adult