Combining MRI and clinical data to detect high relapse risk after the first episode of psychosis

Detecting patients at high relapse risk after the first episode of psychosis (HRR-FEP) could help the clinician adjust the preventive treatment. To develop a tool to detect patients at HRR using their baseline clinical and structural MRI, we followed 227 patients with FEP for 18–24 months and applied MRIPredict. We previously optimized the MRI-based machine-learning parameters (combining unmodulated and modulated gray and white matter and using voxel-based ensemble) in two independent datasets. Patients estimated to be at HRR-FEP showed a substantially increased risk of relapse (hazard ratio = 4.58, P < 0.05). Accuracy was poorer when we only used clinical or MRI data. We thus show the potential of combining clinical and MRI data to detect which individuals are more likely to relapse, who may benefit from increased frequency of visits, and which are unlikely, who may be currently receiving unnecessary prophylactic treatments. We also provide an updated version of the MRIPredict software

Pro/anti-inflammatory disregulation in early psychosis: results from a longitudinal, case-control study

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

Pro-/Anti-inflammatory Dysregulation in Patients With First Episode of Psychosis: Toward an Integrative Inflammatory Hypothesis of Schizophrenia

BACKGROUND: 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. METHODS: 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. RESULTS: 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-PGJ(2) as potential protection factors. DISCUSSION: 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-PGJ(2) might be used as plasmatic biomarker for first episodes of psychosis

Pro/anti-inflammatory disregulation in early psychosis: results from a longitudinal, case-control study

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

Elevated Extracellular Free-Water in a Multicentric First-Episode Psychosis Sample, Decrease During the First 2 Years of Illness.

Recent diffusion imaging studies using free-water (FW) elimination have shown increased FW in gray matter (GM) and white matter (WM) in first-episode psychosis (FEP) and lower corrected fractional anisotropy (FAt) in WM in chronic schizophrenia. However, little is known about the longitudinal stability and clinical significance of these findings. To determine tissue-specific FW and FAt abnormalities in FEP, as part of a multicenter Spanish study, 132 FEP and 108 healthy controls (HC) were clinically characterized and underwent structural and diffusion-weighted MRI scanning. FEP subjects were classified as schizophrenia spectrum disorder (SSD) or non-SSD. Of these subjects, 45 FEP and 41 HC were longitudinally assessed and rescanned after 2 years. FA and FW tissue-specific measurements were cross-sectional and longitudinally compared between groups using voxel-wise analyses in the skeletonized WM and vertex-wise analyses in the GM surface. SSD and non-SSD subjects showed (a) higher baseline FW in temporal regions and in whole GM average (P.adj(SSD vs HC) = .003, P.adj(Non-SSD vs HC) = .040) and (b) lower baseline FAt in several WM tracts. SSD, but not non-SSD, showed (a) higher FW in several WM tracts and in whole WM (P.adj(SSD vs HC)= .049) and (b) a significant FW decrease over time in temporal cortical regions and in whole GM average (P.adj = .011). Increased extracellular FW in the brain is a reliable finding in FEP, and in SSD appears to decrease over the early course of the illness. FAt abnormalities are stable during the first years of psychosis