Papiol, Sergi

[["dc.bibliographiccitation.firstpage","879"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Archives of General Psychiatry"],["dc.bibliographiccitation.lastpage","888"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Malzahn, Dörte"],["dc.contributor.author","Krampe, Henning"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Radyushkin, Konstantin"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Hannke, Kathrin"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Schwerdtfeger, Dayana"],["dc.contributor.author","Thanhäuser, Ivonne"],["dc.contributor.author","Gerchen, Martin Fungisai"],["dc.contributor.author","Ghorbani, Mohammed"],["dc.contributor.author","Gutwinski, Stefan"],["dc.contributor.author","Hilmes, Constanze"],["dc.contributor.author","Leppert, Richard"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Sowislo, Julia"],["dc.contributor.author","Stawicki, Sabina"],["dc.contributor.author","Stödtke, Maren"],["dc.contributor.author","Szuszies, Christoph"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Riggert, Joachim"],["dc.contributor.author","Eckstein, Fritz"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:57Z"],["dc.date.available","2017-09-07T11:46:57Z"],["dc.date.issued","2010"],["dc.description.abstract","Context: Schizophrenia is the collective term for a heterogeneous group of mental disorders with a still obscure biological basis. In particular, the specific contribution of risk or candidate gene variants to the complex schizophrenic phenotype is largely unknown. Objective: To prepare the ground for a novel “phenomics” approach, a unique schizophrenia patient database was established by GRAS (Göttingen Research Association for Schizophrenia), designed to allow association of genetic information with quantifiable phenotypes. Because synaptic dysfunction plays a key role in schizophrenia, the complexin 2 gene (CPLX2) was examined in the first phenotype-based genetic association study (PGAS) of GRAS. Design: Subsequent to a classic case-control approach, we analyzed the contribution of CPLX2 polymorphisms to discrete cognitive domains within the schizophrenic population. To gain mechanistic insight into how certain CPLX2 variants influence gene expression and function, peripheral blood mononuclear cells of patients, Cplxnull mutantmice, and transfected cells were investigated.Setting: Coordinating research center (Max Planck Institute of Experimental Medicine) and 23 collaboratingpsychiatric centers all over Germany.Participants: One thousand seventy-one patients with schizophrenia (DSM-IV) examined by an invariant investigator team, resulting in the GRAS database with more than 3000 phenotypic data points per patient, and 1079 healthy control subjects of comparable ethnicity.Main Outcome Measure: Cognitive performance including executive functioning, reasoning, and verbal learning/memory. Results: Six single-nucleotide polymorphisms, distributed over the whole CPLX2 gene, were found to be highly associated with current cognition of schizophrenic subjects but only marginally with premorbid intelligence. Correspondingly, in Cplx2-null mutant mice, prominent cognitive loss of function was obtained only in combination with a minor brain lesion applied during puberty, modeling a clinically relevant environmental risk (“second hit”) for schizophrenia. In the human CPLX2 gene, 1 of the identified 6 cognition-relevant single-nucleotide polymorphisms, rs3822674 in the 3´ untranslated region, was detected to influence microRNA-498 binding and gene expression. The same marker was associated with differential expression of CPLX2 in peripheral blood mononuclear cells. Conclusions: The PGAS allows identification of markerassociated clinical/biological traits. Current cognitive performance in schizophrenic patients is modified by CPLX2 variants modulating posttranscriptional gene expression"],["dc.identifier.doi","10.1001/archgenpsychiatry.2010.107"],["dc.identifier.fs","577608"],["dc.identifier.gro","3150567"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6097"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7343"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","final"],["dc.rights.access","closedAccess"],["dc.subject","Schizophrenia"],["dc.subject.ddc","610"],["dc.title","Modification of cognitive performance in schizophrenia by complexin 2 gene polymorphisms"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","309"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","319"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Gerchen, Martin F."],["dc.contributor.author","Adamcio, Bartosz"],["dc.contributor.author","Pardo, Luis A."],["dc.contributor.author","Martin, Sabine"],["dc.contributor.author","Malzahn, Dörthe"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Radyushkin, Konstantin A."],["dc.contributor.author","Müller, Michael"],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Riggert, Joachim"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Stühmer, Walter"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:44:13Z"],["dc.date.available","2017-09-07T11:44:13Z"],["dc.date.issued","2011"],["dc.description.abstract","KCNN3, encoding the small conductance calcium-activated potassium channel SK3, harbours a polymorphic CAG repeat in the amino-terminal coding region with yet unproven function. Hypothesizing that KCNN3 genotypes do not influence susceptibility to schizophrenia but modify its phenotype, we explored their contribution to specific schizophrenic symptoms. Using the Gottingen Research Association for Schizophrenia (GRAS) data collection of schizophrenic patients (n=1074), we performed a phenotype-based genetic association study (PGAS) of KCNN3. We show that long CAG repeats in the schizophrenic sample are specifically associated with better performance in higher cognitive tasks, comprising the capacity to discriminate, select and execute (p<0.0001). Long repeats reduce SK3 channel function, as we demonstrate by patch-clamping of transfected HEK293 cells. In contrast, modelling the opposite in mice, i.e. KCNN3 overexpression/channel hyperfunction, leads to selective deficits in higher brain functions comparable to those influenced by SK3 conductance in humans. To conclude, KCNN3 genotypes modify cognitive performance, shown here in a large sample of schizophrenic patients. Reduction of SK3 function may constitute a pharmacological target to improve cognition in schizophrenia and other conditions with cognitive impairment."],["dc.identifier.doi","10.1002/emmm.201100135"],["dc.identifier.gro","3142723"],["dc.identifier.isi","000292277600003"],["dc.identifier.pmid","21433290"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8179"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/159"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1757-4676"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","A CAG repeat polymorphism of KCNN3 predicts SK3 channel function and cognitive performance in schizophrenia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Popovic, David"],["dc.contributor.author","Schmitt, Andrea"],["dc.contributor.author","Kaurani, Lalit"],["dc.contributor.author","Senner, Fanny"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Malchow, Berend"],["dc.contributor.author","Schulze, Thomas G."],["dc.contributor.author","Koutsouleris, Nikolaos"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Fischer, André"],["dc.date.accessioned","2020-12-10T18:44:34Z"],["dc.date.available","2020-12-10T18:44:34Z"],["dc.date.issued","2019"],["dc.description.abstract","Schizophrenia is a severe neuropsychiatric disorder with persistence of symptoms throughout adult life in most of the affected patients. This unfavorable course is associated with multiple episodes and residual symptoms, mainly negative symptoms and cognitive deficits. The neural diathesis-stress model proposes that psychosocial stress acts on a pre-existing vulnerability and thus triggers the symptoms of schizophrenia. Childhood trauma is a severe form of stress that renders individuals more vulnerable to developing schizophrenia; neurobiological effects of such trauma on the endocrine system and epigenetic mechanisms are discussed. Childhood trauma is associated with impaired working memory, executive function, verbal learning, and attention in schizophrenia patients, including those at ultra-high risk to develop psychosis. In these patients, higher levels of childhood trauma were correlated with higher levels of attenuated positive symptoms, general symptoms, and depressive symptoms; lower levels of global functioning; and poorer cognitive performance in visual episodic memory end executive functions. In this review, we discuss effects of specific gene variants that interact with childhood trauma in patients with schizophrenia and describe new findings on the brain structural and functional level. Additive effects between childhood trauma and brain-derived neurotrophic factor methionine carriers on volume loss of the hippocampal subregions cornu ammonis (CA)4/dentate gyrus and CA2/3 have been reported in schizophrenia patients. A functional magnetic resonance imaging study showed that childhood trauma exposure resulted in aberrant function of parietal areas involved in working memory and of visual cortical areas involved in attention. In a theory of mind task reflecting social cognition, childhood trauma was associated with activation of the posterior cingulate gyrus, precuneus, and dorsomedial prefrontal cortex in patients with schizophrenia. In addition, decreased connectivity was shown between the posterior cingulate/precuneus region and the amygdala in patients with high levels of physical neglect and sexual abuse during childhood, suggesting that disturbances in specific brain networks underlie cognitive abilities. Finally, we discuss some of the questionnaires that are commonly used to assess childhood trauma and outline possibilities to use recent biostatistical methods, such as machine learning, to analyze the resulting datasets."],["dc.identifier.doi","10.3389/fnins.2019.00274"],["dc.identifier.eissn","1662-453X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78509"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-453X"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","528"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","539"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Hagemeyer, Nora"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Hofer, Sabine"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Gerwig, Ulrike C."],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Wieser, Georg L."],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Gurvich, Artem"],["dc.contributor.author","Heckers, Stephan H."],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-08-25T10:14:17Z"],["dc.date.available","2017-08-25T10:14:17Z"],["dc.date.issued","2012"],["dc.description.abstract","Severe mental illnesses have been linked to white matter abnormalities, documented by postmortem studies. However, cause and effect have remained difficult to distinguish. CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase) is among the oligodendrocyte/myelin-associated genes most robustly reduced on mRNA and protein level in brains of schizophrenic, bipolar or major depressive patients. This suggests that CNP reduction might be critical for a more general disease process and not restricted to a single diagnostic category. We show here that reduced expression of CNP is the primary cause of a distinct behavioural phenotype, seen only upon aging as an additional 'pro-inflammatory hit'. This phenotype is strikingly similar in Cnp heterozygous mice and patients with mental disease carrying the AA genotype at CNP SNP rs2070106. The characteristic features in both species with their partial CNP 'loss-of-function' genotype are best described as 'catatonia-depression' syndrome. As a consequence of perturbed CNP expression, mice show secondary low-grade inflammation/neurodegeneration. Analogously, in man, diffusion tensor imaging points to axonal loss in the frontal corpus callosum. To conclude, subtle white matter abnormalities inducing neurodegenerative changes can cause/amplify psychiatric diseases."],["dc.identifier.doi","10.1002/emmm.201200230"],["dc.identifier.gro","3150560"],["dc.identifier.pmid","22473874"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7776"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7334"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","A myelin gene causative of a catatonia-depression syndrome upon aging"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","47"],["dc.bibliographiccitation.issue","Suppl 9"],["dc.bibliographiccitation.journal","BMC Proceedings"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Yasmeen, Summaira"],["dc.contributor.author","Burger, Patricia"],["dc.contributor.author","Friedrichs, Stefanie"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Bickeböller, Heike"],["dc.date.accessioned","2019-07-09T11:45:54Z"],["dc.date.available","2019-07-09T11:45:54Z"],["dc.date.issued","2018"],["dc.description.abstract","In GAW20, we investigated the association of specific genetic regions of interest (ROIs) with log-transformed triglyceride (TG) levels following lipid-lowering medication using epigenetic and genetic markers. The goal was to incorporate kernels for cytosine-phosphate-guanine (CpG) markers and compare the kernels to a purely parametric model. Post-treatment TG levels were investigated for post-methylation data at CpG sites and region-specific SNPs and adjusted for pre-treatment TG levels and age, in independent individuals only (real data: n = 150; simulated data, replicate 84: n = 111). In both data sets, our single-CpG-marker results using kernels and linear regression were in good agreement. In the real data, we investigated the introns of the CPT1A gene previously reported as associated with TG levels as separate ROIs, and were able to find hints of an association of cg17058475 and cg00574958 with post-treatment TG levels. In the simulated data, we investigated a total of 10 regions, in which the 5 causal and 5 non-causal markers lie, respectively, with increased methylation variances, yielding plausible results for the 3 window sizes. Overall, this indicates that kernels for CpG markers are feasible. An interaction regression model for the causal SNP with the nearest CpG marker identified an effect for the SNPs with the three greatest heritabilities simulated. The simulation model assumed full SNP effect only for unmethylated regions decreasing to zero in the case of full methylation. Thus, in the context of a clear candidate setting, interaction between epigenetic and genetic data may enhance information, albeit nominally, even with small sample sizes. Relieving the burden of multiple testing, developing kernels further to analyze data from multiple omics jointly is well warranted."],["dc.identifier.doi","10.1186/s12919-018-0154-5"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15339"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59332"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Relating drug response to epigenetic and genetic markers using a region-based kernel score test"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","284"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Translational Psychiatry"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Keeser, Daniel"],["dc.contributor.author","Hasan, Alkomiet"],["dc.contributor.author","Schneider-Axmann, Thomas"],["dc.contributor.author","Raabe, Florian"],["dc.contributor.author","Degenhardt, Franziska"],["dc.contributor.author","Rossner, Moritz J."],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Wobrock, Thomas"],["dc.contributor.author","Schmitt, Andrea"],["dc.contributor.author","Malchow, Berend"],["dc.contributor.author","Falkai, Peter Gaston"],["dc.date.accessioned","2019-12-18T14:16:43Z"],["dc.date.available","2019-12-18T14:16:43Z"],["dc.date.issued","2019"],["dc.description.abstract","Hippocampal volume decrease is a structural hallmark of schizophrenia (SCZ), and convergent evidence from postmortem and imaging studies suggests that it may be explained by changes in the cytoarchitecture of the cornu ammonis 4 (CA4) and dentate gyrus (DG) subfields. Increasing evidence indicates that aerobic exercise increases hippocampal volume in CA subfields and improves cognition in SCZ patients. Previous studies showed that the effects of exercise on the hippocampus might be connected to the polygenic burden of SCZ risk variants. However, little is known about cell type-specific genetic contributions to these structural changes. In this secondary analysis, we evaluated the modulatory role of cell type-specific SCZ polygenic risk scores (PRS) on volume changes in the CA1, CA2/3, and CA4/DG subfields over time. We studied 20 multi-episode SCZ patients and 23 healthy controls who performed aerobic exercise, and 21 multi-episode SCZ patients allocated to a control intervention (table soccer) for 3 months. Magnetic resonance imaging-based assessments were performed with FreeSurfer at baseline and after 3 months. The analyses showed that the polygenic burden associated with oligodendrocyte precursor cells (OPC) and radial glia (RG) significantly influenced the volume changes between baseline and 3 months in the CA4/DG subfield in SCZ patients performing aerobic exercise. A higher OPC- or RG-associated genetic risk burden was associated with a less pronounced volume increase or even a decrease in CA4/DG during the exercise intervention. We hypothesize that SCZ cell type-specific polygenic risk modulates the aerobic exercise-induced neuroplastic processes in the hippocampus."],["dc.identifier.doi","10.1038/s41398-019-0618-z"],["dc.identifier.pmid","31712617"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16922"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62762"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2158-3188"],["dc.relation.issn","2158-3188"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Polygenic burden associated to oligodendrocyte precursor cells and radial glia influences the hippocampal volume changes induced by aerobic exercise in schizophrenia patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","91"],["dc.bibliographiccitation.journal","BMC Psychiatry"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Gerchen, Martin Fungisai"],["dc.contributor.author","Ackermann, Verena"],["dc.contributor.author","Tarami, Asieh"],["dc.contributor.author","Treitz, Annika"],["dc.contributor.author","Flögel, Marlene"],["dc.contributor.author","Adler, Lothar"],["dc.contributor.author","Aldenhoff, Josef B."],["dc.contributor.author","Becker-Emner, Marianne"],["dc.contributor.author","Becker, Thomas"],["dc.contributor.author","Czernik, Adelheid"],["dc.contributor.author","Dose, Matthias"],["dc.contributor.author","Folkerts, Here"],["dc.contributor.author","Freese, Roland"],["dc.contributor.author","Guenther, Rolf"],["dc.contributor.author","Herpertz, Sabine"],["dc.contributor.author","Hesse, Dirk"],["dc.contributor.author","Kruse, Gunther"],["dc.contributor.author","Kunze, Heinrich"],["dc.contributor.author","Franz, Michael"],["dc.contributor.author","Lohrer, Frank"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Mielke, Andreas"],["dc.contributor.author","Müller-Isberner, Rüdiger"],["dc.contributor.author","Oestereich, Cornelia"],["dc.contributor.author","Pajonk, Frank-Gerald"],["dc.contributor.author","Pollmächer, Thomas"],["dc.contributor.author","Schneider, Udo"],["dc.contributor.author","Schwarz, Hans-Joachim"],["dc.contributor.author","Kröner-Herwig, Birgit"],["dc.contributor.author","Havemann-Reinecke, Ursula"],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Stühmer, Walter"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:37Z"],["dc.date.available","2017-09-07T11:46:37Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia. Methods: For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected. Results: The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail. Conclusions: The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes."],["dc.format.extent","20"],["dc.identifier.doi","10.1186/1471-244X-10-91"],["dc.identifier.gro","3150558"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5803"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7333"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","The cross-sectional GRAS sample: a comprehensive phenotypical data collection of schizophrenic patients"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","386"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Translational Psychiatry"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Wendel, Bernadette"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Andlauer, Till F. M."],["dc.contributor.author","Zimmermann, Jörg"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Spitzer, Carsten"],["dc.contributor.author","Senner, Fanny"],["dc.contributor.author","Schulte, Eva C."],["dc.contributor.author","Schmauß, Max"],["dc.contributor.author","Heilbronner, Urs"],["dc.date.accessioned","2021-08-12T07:44:54Z"],["dc.date.available","2021-08-12T07:44:54Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Executive functions are metacognitive capabilities that control and coordinate mental processes. In the transdiagnostic PsyCourse Study, comprising patients of the affective-to-psychotic spectrum and controls, we investigated the genetic basis of the time course of two core executive subfunctions: set-shifting (Trail Making Test, part B (TMT-B)) and updating (Verbal Digit Span backwards) in 1338 genotyped individuals. Time course was assessed with four measurement points, each 6 months apart. Compared to the initial assessment, executive performance improved across diagnostic groups. We performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with performance change over time by testing for SNP-by-time interactions using linear mixed models. We identified nine genome-wide significant SNPs for TMT-B in strong linkage disequilibrium with each other on chromosome 5. These were associated with decreased performance on the continuous TMT-B score across time. Variant rs150547358 had the lowest P value = 7.2 × 10 −10 with effect estimate beta = 1.16 (95% c.i.: 1.11, 1.22). Implementing data of the FOR2107 consortium (1795 individuals), we replicated these findings for the SNP rs150547358 ( P value = 0.015), analyzing the difference of the two available measurement points two years apart. In the replication study, rs150547358 exhibited a similar effect estimate beta = 0.85 (95% c.i.: 0.74, 0.97). Our study demonstrates that longitudinally measured phenotypes have the potential to unmask novel associations, adding time as a dimension to the effects of genomics."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.1038/s41398-021-01510-8"],["dc.identifier.pii","1510"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88326"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation.eissn","2158-3188"],["dc.rights","CC BY 4.0"],["dc.title","A genome-wide association study of the longitudinal course of executive functions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e45"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Translational Psychiatry"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Malzahn, Dörte"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Stefansson, Hreinn"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:32Z"],["dc.date.available","2017-09-07T11:46:32Z"],["dc.date.issued","2011"],["dc.description.abstract","Genotype–phenotype correlations of common monogenic diseases revealed that the degree of deviation of mutant genes from wild-type structure and function often predicts disease onset and severity. In complex disorders such as schizophrenia, the overall genetic risk is still often >50% but genotype–phenotype relationships are unclear. Recent genome-wide association studies (GWAS) replicated a risk for several single-nucleotide polymorphisms (SNPs) regarding the endpoint diagnosis of schizophrenia. The biological relevance of these SNPs, however, for phenotypes or severity of schizophrenia has remained obscure. We hypothesized that the GWAS ‘top-10’ should as single markers, but even more so upon their accumulation, display associations with lead features of schizophrenia, namely positive and negative symptoms, cognitive deficits and neurological signs (including catatonia), and/or with age of onset of the disease prodrome as developmental readout and predictor of disease severity. For testing this hypothesis, we took an approach complementary to GWAS, and performed a phenotype-based genetic association study (PGAS). We utilized the to our knowledge worldwide largest phenotypical database of schizophrenic patients (n>1000), the GRAS (Göttingen Research Association for Schizophrenia) Data Collection. We found that the ‘top-10’ GWAS-identified risk SNPs neither as single markers nor when explored in the sense of a cumulative genetic risk, have any predictive value for disease onset or severity in the schizophrenic patients, as demonstrated across all core symptoms. We conclude that GWAS does not extract disease genes of general significance in schizophrenia, but may yield, on a hypothesis-free basis, candidate genes relevant for defining disease subgroups."],["dc.format.extent","6"],["dc.identifier.doi","10.1038/tp.2011.43"],["dc.identifier.gro","3150533"],["dc.identifier.pmid","22833191"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11388"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7305"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.subject","Cambridge neurological inventory; cognition; GWAS; PGAS; positive and negative syndrome scale; prodrome"],["dc.title","Dissociation of accumulated genetic risk and disease severity in patients with schizophrenia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","68"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Bipolar Disorders"],["dc.bibliographiccitation.lastpage","75"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Kalman, Janos L."],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Forstner, Andreas J."],["dc.contributor.author","Heilbronner, Urs"],["dc.contributor.author","Degenhardt, Franziska"],["dc.contributor.author","Strohmaier, Jana"],["dc.contributor.author","Adli, Mazda"],["dc.contributor.author","Adorjan, Kristina"],["dc.contributor.author","Akula, Nirmala"],["dc.contributor.author","Alda, Martin"],["dc.contributor.author","Schulze, Thomas G."],["dc.date.accessioned","2019-07-09T11:50:29Z"],["dc.date.available","2019-07-09T11:50:29Z"],["dc.date.issued","2019"],["dc.description.abstract","OBJECTIVES: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients. METHODS: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models. RESULTS: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. CONCLUSIONS: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype."],["dc.identifier.doi","10.1111/bdi.12659"],["dc.identifier.pmid","29956436"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15948"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59781"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1399-5618"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]