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

Little 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. © 2021, The Author(s)

The polygenic basis of relapse after a first episode of schizophrenia

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11–0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse

PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis

RATIONALE: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. OBJECTIVE: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. METHODS AND RESULTS: A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, β=0.40, P=1.70×10-9). CONCLUSIONS: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci

Geogaceta.

Ponencia presentada en la 34a Sesión Científica de la Sociedad Geológica de España, celebrada en la Facultad de Ciencias de la Universidad del País Vasco, Campus de Leioa (Bilbao) el día 30 de mayo de 200

Geogaceta.

Ponencia presentada en la 34a Sesión Científica de la Sociedad Geológica de España, celebrada en la Facultad de Ciencias de la Universidad del País Vasco, Campus de Leioa (Bilbao) el día 30 de mayo de 200

Diagenesis of the inoceramid shells from the Castro Island (latest Coniacian-lower Santonian, Basque-Cantabrian Basin): petrological and isotopic evidences

Pétrographie and isotopic (á!80 and a13C) analyses have been carried out on inoceramid shells from shallow-marine limestone-marl couplets at the Castro Island section (latest Coniacian-lower Santonian, Basque-Cantabrian Basin), in order to determine their diagenetic alteration. Results show that the prismatic microstructure of the shells was mainly affected by silica replacement during diagenesis, but very little compaction, cementation and recrystallization occurred. However, these changes do not seem to have modified largely the isotopic composition of the inoceramids, as supported by the low luminescence intensity that show all the shells. In addition, à780 and al3C mean values from inoceramids included in limestones are heavier than those from inocermids in marls, which confirms that the isotopic values were influenced by a paleoceanographic circulation model with estuarine and anti-estuarine regimen

Diagenetic modifications from microstructure of inoceramid shells (Bivalvia) of the Plentzia Formation (Santonian, Basque Arc)

noceramid shells, from the Santonian of the Basque Arc, have been tested to determine the preservation of their original prismatic microstructure formed by low magnesium calcite (LMC). Petrography and cathodoluminescence (CL) show, although they have good aspect, shells underwent a clear burial diagenesis. They suffered replacement by fibrous silica; strong compaction with pressure solution; and a final stage of cementation. Under CL the prisms show yellow to red luminescence with an evident cationic modification, and in addition, it allows to see the advance of the diagenetic fluids through prismatic boundaries, and to establish the chronology of the diagenetic processes, which altered selectively their original microstructure and compositio

Palaeoceanographic data provided by the foraminifers of the Barrika section (Santonian of the Rasque Arc)

Analyses carried out on benthonic foraminiferal assemblages of the Barrika section (Basque Arc) are part of a multidisciplinary research with the main subject of understanding the palaeoceanographic events that took place at the end of the Cretaceous within the Basque Basin. The Barrika section has been dated as uppermost early Santonian-upper Santonian by means of the planktonic species Dicarinella concavata and Dicarinella asymetrica. It is additionally confirmed by the detection of benthonic species such as Eponides concinna, Vemeuilina muensteri, Tritaxia capitosa, and Reussella szajnochae praecursor. A total of 130 benthonic species have been identified, which clearly correspond to deep marine water microfauna, except that from shallow waters at the top of the section. In this context, some of the aspects about the palaeoenvironmental variations detected in Barrika section are crucially provided by qualitative and quantitative changes of the foraminiferal assemblages, specific diversity changes of the microfauna, and both the rate between different kinds of benthonic wall structures, and the ratio between benthonics and planktonics. Thus, the dominant foraminiferal assemblages, the great percentage of agglutinated tests, and the high values of the oceanicity index suggest a cool well-oxygenated bathyal waters palaeoenvironment for most of the section. However, the top of the section is particularly marked by a relative sea-level fall, that could reach its maximum at the end of the Santonian, producing a dramatic change to an internal platform palaeoenvironment. This event may have probably been the response to the global regression occurred at 85 M.a

Geochemical and micropalaeontologic signals as palaeoceanographic event markers from the Santonian of the Basque Arc

Comparative study of micropalaeontologic (planktonic and benthic foraminifers) and isotopic (8,80 and 5'3C values from inoceramids and whole rock) data from the Santonian of the Barrika section (Basque Arc, northern Spain) shows the existence of four events, each one with different biotic and geochemical signals. Diagenetic alteration of isotopic profiles (5,eO and 8I3C) have not been so severe to delete completely the geochemical signals from inoceramids and whole rock. As a consequence, events 1st, 2nd and 3rd show a 5lsO positive excursion (cooling) and sea level falls; however the 4th event marks a global regression at 85 m.y., that could have caused strong local alteration of the planktonic and benthic foraminifer assemblages. In this case, the eustatic fall shows a S'0O negative excursion, that could be related to meteoric cementation, due to sea level lowstan