Pro-/Antiinflammatory Dysregulation in Early Psychosis: Results from a 1-Year Follow-Up Study

Abstract

Background:Previous studies indicated a systemic deregulation of the pro-/antiinflammatory balance in subjects after 6 months of a first psychotic episode. This disruption was reexamined 12 months after diagnosis to identify potential risk/protective factors and associations with symptom severity.Methods:Eighty-five subjects were followed during 12 months and the determination of the same pro-/antiinflammatory mediators was carried out in plasma and peripheral blood mononuclear cells. Multivariate logistic regression analyses were used to identify risk/protective factors. 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.Results:This study suggests a more severe systemic pro-/antiinflammatory deregulation than in earlier pathological stages in first psychotic episode, because not only were intracellular components of the inflammatory response increased but also the majority of soluble elements. Nitrite plasma levels and cyclooxygenase-2 expression in peripheral blood mononuclear cells are reliable potential risk factors and 15d-prostaglandin-J2 plasma levels a protection biomarker. An interesting relationship exists between antipsychotic dose and the levels of prostaglandin-E2 (inverse) and 15d-prostaglandin-J2 (direct). An inverse relationship between the Global Assessment of Functioning scale and lipid peroxidation is also present.Conclusions: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.

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia

“…[13][14][15] A significant increase in intracellular components of the NF-κB-dependent main proinflammatory pathway (iNOS, COX-2 expression, and NO 2 and MDA levels), along with a significant decrease in the anti-inflammatory receptor PPARγ, have been reported in patients with FEPS and chronic schizophrenia. However, in our PFC samples, these proinflammatory parameters remained unaltered, and the expression of PPARγ increased.…”

“…Recently, a peripheral imbalance of these pro-/antiinflammatory pathways was reported in patients with firstepisode psychosis (FEP) and in patients with chronic schizophrenia with an acutely exacerbated condition. [13][14][15] However, only a few studies report altered TLR expression or response to immune stimuli in patients with schizophrenia. 16,17 A recent update reviews the randomized controlled trials of the efficacy of anti-inflammatory compounds in patients with schizophrenia.…”

Effects of electroconvulsive therapy in the systemic inflammatory balance of patients with severe mental disorder

“…These studies included nearly 400 subjects with schizophrenia‐related disorders, 674 with BD, 148 with major depressive disorder (MDD), and 643 healthy subjects. In particular, patients in an early phase of a psychotic disorder showed increased levels of pro‐inflammatory NFκB, iNOS, and COX‐2, while the anti‐inflammatory inhibitory subunit of NFκB, 15d‐PGJ 2 , and PPARγ expression and transcriptional activity were lower . In patients with established schizophrenia, NFκB, iNOS, COX‐1, COX‐2, TLR4, and PGE2 expression were found to be elevated, while the anti‐inflammatory prostaglandin 15d‐PGJ 2 and its nuclear receptor PPARγ were decreased .…”

“…Following this hypothesis, a successful treatment would help to normalize the inflammatory imbalance that some of these individuals present …”

The effect of excess weight on circulating inflammatory cytokines in drug-naïve first-episode psychosis individuals

“…In addition, a proinflammatory state has been repeatedly associated with first-episode psychosis (FEP) [5,11,12,15], especially in women, overweight patients, and tobacco users [9,10]. However, no previous study has addressed the direct effect of BMI on basal serum cytokines in FEP individuals.…”