scholarly journals A longitudinal study of gene expression in first-episode schizophrenia; exploring relapse mechanisms by co-expression analysis in peripheral blood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
P. Gassó ◽  
N. Rodríguez ◽  
A. Martínez-Pinteño ◽  
G. Mezquida ◽  
M. Ribeiro ◽  
...  

AbstractLittle is known about the pathophysiological mechanisms of relapse in first-episode schizophrenia, which limits the study of potential biomarkers. To explore relapse mechanisms and identify potential biomarkers for relapse prediction, we analyzed gene expression in peripheral blood in a cohort of first-episode schizophrenia patients with less than 5 years of evolution who had been evaluated over a 3-year follow-up period. A total of 91 participants of the 2EPs project formed the sample for baseline gene expression analysis. Of these, 67 provided biological samples at follow-up (36 after 3 years and 31 at relapse). Gene expression was assessed using the Clariom S Human Array. Weighted gene co-expression network analysis was applied to identify modules of co-expressed genes and to analyze their preservation after 3 years of follow-up or at relapse. Among the 25 modules identified, one module was semi-conserved at relapse (DarkTurquoise) and was enriched with risk genes for schizophrenia, showing a dysregulation of the TCF4 gene network in the module. Two modules were semi-conserved both at relapse and after 3 years of follow-up (DarkRed and DarkGrey) and were found to be biologically associated with protein modification and protein location processes. Higher expression of DarkRed genes was associated with higher risk of suffering a relapse and early appearance of relapse (p = 0.045). Our findings suggest that a dysregulation of the TCF4 network could be an important step in the biological process that leads to relapse and suggest that genes related to the ubiquitin proteosome system could be potential biomarkers of relapse.

2018 ◽  
Vol 189 (5) ◽  
pp. 529-540 ◽  
Author(s):  
Andreas Lamkowski ◽  
Matthias Kreitlow ◽  
Jörg Radunz ◽  
Martin Willenbockel ◽  
Frank Sabath ◽  
...  

2008 ◽  
Vol 38 (8) ◽  
pp. 1141-1146 ◽  
Author(s):  
P. Whitty ◽  
M. Clarke ◽  
O. McTigue ◽  
S. Browne ◽  
M. Kamali ◽  
...  

BackgroundThe outcome of schizophrenia appears to be more favourable than once thought. However, methodological issues, including the reliance on diagnosis at first presentation have limited the validity of outcome studies to date.MethodWe conducted a first-episode follow-up study of 97 patients with DSM-IV schizophrenia over the first 4 years of illness. First presentation and follow-up assessments were compared using paired t tests and a forced-entry regression analysis was used to determine prognostic variables.ResultsThere were significant improvements in positive and negative symptoms and global assessment of functioning between first presentation and follow-up. At first presentation, fewer negative symptoms (t=−3.40, p<0.01), more years spent in education (t=3.25, p<0.01), and a shorter duration of untreated psychosis (DUP) (t=−2.77, p<0.01) significantly predicted a better outcome at follow-up.ConclusionsThe outcome of schizophrenia may not be as pessimistic as once thought and most patients did not display a downward deteriorating course of illness. This study supports the relationship between DUP and outcome beyond the early stages of illness.


1992 ◽  
Vol 161 (4) ◽  
pp. 496-500 ◽  
Author(s):  
Robin G. McCreadie ◽  
David H. Wiles ◽  
Martin G. Livingston ◽  
James A. G. Watt ◽  
J. G. Greene ◽  
...  

Forty-four schizophrenic patients were followed up for five years after their first admission to hospital for a first episode of illness. Thirteen (30%) of 43 patients had not relapsed; 28 of the 30 patients who did relapse did so within the first 42 months. The relapses occurred despite antipsychotic drug therapy. Also, 24% of patients had at least one course of ECT. Only 19% of the patients at five years were in open employment; unemployment was strongly associated with relapse. Eighteen per cent had neither relapses nor schizophrenic symptoms at follow-up. Poor outcome at five years was associated with greater psychological distress among relatives at first admission. At five years 43% of relatives continued to show case level psychological stress.


2017 ◽  
Vol 4 (3) ◽  
pp. e337 ◽  
Author(s):  
Sundararajan Srinivasan ◽  
Marco Di Dario ◽  
Alessandra Russo ◽  
Ramesh Menon ◽  
Elena Brini ◽  
...  

Objective:To perform systematic transcriptomic analysis of multiple sclerosis (MS) risk genes in peripheral blood mononuclear cells (PBMCs) of subjects with distinct MS stages and describe the pathways characterized by dysregulated gene expressions.Methods:We monitored gene expression levels in PBMCs from 3 independent cohorts for a total of 297 cases (including clinically isolated syndromes (CIS), relapsing-remitting MS, primary and secondary progressive MS) and 96 healthy controls by distinct microarray platforms and quantitative PCR. Differential expression and pathway analyses for distinct MS stages were defined and validated by literature mining.Results:Genes located in the vicinity of MS risk variants displayed altered expression in peripheral blood at distinct stages of MS compared with the healthy population. The frequency of dysregulation was significantly higher than expected in CIS and progressive forms of MS. Pathway analysis for each MS stage–specific gene list showed that dysregulated genes contributed to pathogenic processes with scientific evidence in MS.Conclusions:Systematic gene expression analysis in PBMCs highlighted selective dysregulation of MS susceptibility genes playing a role in novel and well-known pathogenic pathways.


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