Benseler, Fritz

[["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","340"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part B: Neuropsychiatric Genetics"],["dc.bibliographiccitation.lastpage","345"],["dc.bibliographiccitation.volume","156B"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Schwab, Markus H."],["dc.contributor.author","Jahn, Henriette"],["dc.contributor.author","Gunkel, Stefan"],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:36Z"],["dc.date.available","2017-09-07T11:46:36Z"],["dc.date.issued","2011"],["dc.description.abstract","By pure endpoint diagnosis of the disease, the risk of developing schizophrenia has been repeatedly associated with specific variants of the neuregulin1 (NRG1) gene. However, the role of NRG1 in the etiology of schizophrenia has remained unclear. Since Nrg1 serves vital functions in early brain development of mice, we hypothesized that human NRG1 alleles codetermine developmentally influenced readouts of the disease: age of onset and positive symptom severity. We analyzed 1,071 comprehensively phenotyped schizophrenic/schizoaffective patients, diagnosed according to DSM-IV-TR, from the GRAS (Göttingen Research Association for Schizophrenia) Data Collection for genetic variability in the Icelandic region of risk in the NRG1 gene. For the case-control analysis part of the study, we included 1,056 healthy individuals with comparable ethnicity. The phenotype-based genetic association study (PGAS) was performed on the GRAS sample. Instead of a risk constellation, we detected that several haplotypic variants of NRG1 were, unexpectedly, less frequent in the schizophrenic than in the control sample (mean OR=0.78, range between 0.68 and 0.85). In the PGAS we found that these \"protective\" NRG1 variants are specifically underrepresented in subgroups of schizophrenic subjects with early age of onset and high positive symptom load. The GRAS Data Collection as a prerequisite for PGAS has enabled us to associate protective NRG1 genotypes with later onset and milder course of schizophrenia."],["dc.identifier.doi","10.1002/ajmg.b.31168"],["dc.identifier.gro","3150547"],["dc.identifier.pmid","21234898"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7321"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","A phenotype-based genetic association study reveals the contribution of neuregulin1 gene variants to age of onset and positive symptom severity in schizophrenia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["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.firstpage","1565"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","1579"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Kastner, Anne"],["dc.contributor.author","Poggi, Giulia"],["dc.contributor.author","Mitjans, Marina"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Hartmann, Annette M."],["dc.contributor.author","Van der Auwera, Sandra"],["dc.contributor.author","Sananbenesi, Farahnaz"],["dc.contributor.author","Krueger-Burg, Dilja"],["dc.contributor.author","Matuszko, Gabriela"],["dc.contributor.author","Brosi, Cornelia"],["dc.contributor.author","Homuth, Georg"],["dc.contributor.author","Völzke, H."],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Bagni, Claudia"],["dc.contributor.author","Fischer, Utz"],["dc.contributor.author","Dityatev, Alexander"],["dc.contributor.author","Grabe, Hans-Jörgen"],["dc.contributor.author","Rujescu, Dan"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:54:49Z"],["dc.date.available","2017-09-07T11:54:49Z"],["dc.date.issued","2015"],["dc.description.abstract","Fragile X syndrome (FXS) is mostly caused by a CGG triplet expansion in the fragile X mental retardation 1 gene (FMR1). Up to 60% of affected males fulfill criteria for autism spectrum disorder (ASD), making FXS the most frequent monogenetic cause of syndromic ASD. It is unknown, however, whether normal variants (independent of mutations) in the fragile X gene family (FMR1, FXR1, FXR2) and in FMR2 modulate autistic features. Here, we report an accumulation model of 8 SNPs in these genes, associated with autistic traits in a discovery sample of male patients with schizophrenia (N = 692) and three independent replicate samples: patients with schizophrenia (N = 626), patients with other psychiatric diagnoses (N = 111) and a general population sample (N = 2005). For first mechanistic insight, we contrasted microRNA expression in peripheral blood mononuclear cells of selected extreme group subjects with high-versus low-risk constellation regarding the accumulation model. Thereby, the brain-expressed miR-181 species emerged as potential \"umbrella regulator\", with several seed matches across the fragile X gene family and FMR2. To conclude, normal variation in these genes contributes to the continuum of autistic phenotypes."],["dc.identifier.doi","10.15252/emmm.201505696"],["dc.identifier.gro","3141771"],["dc.identifier.isi","000368135400005"],["dc.identifier.pmid","26612855"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12871"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/890"],["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.eissn","1757-4684"],["dc.relation.issn","1757-4676"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Accumulated common variants in the broader fragile X gene family modulate autistic phenotypes"],["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.firstpage","337"],["dc.bibliographiccitation.issue","2-3"],["dc.bibliographiccitation.journal","Schizophrenia Research"],["dc.bibliographiccitation.lastpage","338"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Klaus, Sabrina"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Malzahn, Doerthe"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Radyushkin, Konstantin A."],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Riggert, Joachim"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Bickeboeller, Heike"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2018-11-07T08:44:54Z"],["dc.date.available","2018-11-07T08:44:54Z"],["dc.date.issued","2010"],["dc.identifier.isi","000276936800585"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20301"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eventlocation","Florence, ITALY"],["dc.relation.issn","0920-9964"],["dc.title","Complexin2 Gene Polymorphisms Modify Cognitive Performance in Schizophrenia"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","337"],["dc.bibliographiccitation.issue","2-3"],["dc.bibliographiccitation.journal","Schizophrenia Research"],["dc.bibliographiccitation.lastpage","338"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Klaus, Sabrina"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Malzahn, Dörthe"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Radyushkin, Konstantin"],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2022-03-01T11:45:23Z"],["dc.date.available","2022-03-01T11:45:23Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1016/j.schres.2010.02.583"],["dc.identifier.pii","S0920996410006687"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103308"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0920-9964"],["dc.title","Complexin2 Gene Polymorphisms Modify Cognitive Performance in Schizophrenia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]