Malzahn, Dörthe

[["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.artnumber","2671"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Heide, Ev Christin"],["dc.contributor.author","Bindila, Laura"],["dc.contributor.author","Post, Julia Maria"],["dc.contributor.author","Malzahn, Dörthe"],["dc.contributor.author","Lutz, Beat"],["dc.contributor.author","Seele, Jana"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Ribes, Sandra"],["dc.date.accessioned","2019-07-09T11:49:37Z"],["dc.date.available","2019-07-09T11:49:37Z"],["dc.date.issued","2018"],["dc.description.abstract","Easy-to-achieve interventions to promote healthy longevity are desired to diminish the incidence and severity of infections, as well as associated disability upon recovery. The dietary supplement palmitoylethanolamide (PEA) exerts anti-inflammatory and neuroprotective properties. Here, we investigated the effect of prophylactic PEA on the early immune response, clinical course, and survival of old mice after intracerebral E. coli K1 infection. Nineteen-month-old wild type mice were treated intraperitoneally with two doses of either 0.1 mg PEA/kg in 250 μl vehicle solution (n = 19) or with 250 μl vehicle solution only as controls (n = 19), 12 h and 30 min prior to intracerebral E. coli K1 infection. The intraperitoneal route was chosen to reduce distress in mice and to ensure exact dosing. Survival time, bacterial loads in cerebellum, blood, spleen, liver, and microglia counts and activation scores in the brain were evaluated. We measured the levels of IL-1β, IL-6, MIP-1α, and CXCL1 in cerebellum and spleen, as well as of bioactive lipids in serum in PEA- and vehicle-treated animals 24 h after infection. In the absence of antibiotic therapy, the median survival time of PEA-pre-treated infected mice was prolonged by 18 h compared to mice of the vehicle-pre-treated infected group (P = 0.031). PEA prophylaxis delayed the onset of clinical symptoms (P = 0.037). This protective effect was associated with lower bacterial loads in the spleen, liver, and blood compared to those of vehicle-injected animals (P ≤ 0.037). PEA-pre-treated animals showed diminished levels of pro-inflammatory cytokines and chemokines in spleen 24 h after infection, as well as reduced serum concentrations of arachidonic acid and of one of its metabolites, 20-hydroxyeicosatetraenoic acid. In the brain, prophylactic PEA tended to reduce bacterial titers and attenuated microglial activation in aged infected animals (P = 0.042). Our findings suggest that prophylactic PEA can counteract infection associated detrimental responses in old animals. Accordingly, PEA treatment slowed the onset of infection symptoms and prolonged the survival of old infected mice. In a clinical setting, prophylactic administration of PEA might extend the potential therapeutic window where antibiotic therapy can be initiated to rescue elderly patients."],["dc.identifier.doi","10.3389/fimmu.2018.02671"],["dc.identifier.pmid","30505308"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15727"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59593"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Prophylactic Palmitoylethanolamide Prolongs Survival and Decreases Detrimental Inflammation in Aged Mice With Bacterial Meningitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","156"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Neuropsychopharmacology : The Journal of the European College of Neuropsychopharmacology"],["dc.bibliographiccitation.lastpage","170"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Budde, Monika"],["dc.contributor.author","Friedrichs, Stefanie"],["dc.contributor.author","Alliey-Rodriguez, Ney"],["dc.contributor.author","Ament, Seth"],["dc.contributor.author","Badner, Judith A."],["dc.contributor.author","Berrettini, Wade H."],["dc.contributor.author","Bloss, Cinnamon S."],["dc.contributor.author","Byerley, William"],["dc.contributor.author","Cichon, Sven"],["dc.contributor.author","Comes, Ashley L."],["dc.contributor.author","Coryell, William"],["dc.contributor.author","Craig, David W."],["dc.contributor.author","Degenhardt, Franziska"],["dc.contributor.author","Edenberg, Howard J."],["dc.contributor.author","Foroud, Tatiana"],["dc.contributor.author","Forstner, Andreas J."],["dc.contributor.author","Frank, Josef"],["dc.contributor.author","Gershon, Elliot S."],["dc.contributor.author","Goes, Fernando S."],["dc.contributor.author","Greenwood, Tiffany A."],["dc.contributor.author","Guo, Yiran"],["dc.contributor.author","Hipolito, Maria"],["dc.contributor.author","Hood, Leroy"],["dc.contributor.author","Keating, Brendan J."],["dc.contributor.author","Koller, Daniel L."],["dc.contributor.author","Lawson, William B."],["dc.contributor.author","Liu, Chunyu"],["dc.contributor.author","Mahon, Pamela B."],["dc.contributor.author","McInnis, Melvin G."],["dc.contributor.author","McMahon, Francis J."],["dc.contributor.author","Meier, Sandra M."],["dc.contributor.author","Mühleisen, Thomas W."],["dc.contributor.author","Murray, Sarah S."],["dc.contributor.author","Nievergelt, Caroline M."],["dc.contributor.author","Nurnberger, John I."],["dc.contributor.author","Nwulia, Evaristus A."],["dc.contributor.author","Potash, James B."],["dc.contributor.author","Quarless, Danjuma"],["dc.contributor.author","Rice, John"],["dc.contributor.author","Roach, Jared C."],["dc.contributor.author","Scheftner, William A."],["dc.contributor.author","Schork, Nicholas J."],["dc.contributor.author","Shekhtman, Tatyana"],["dc.contributor.author","Shilling, Paul D."],["dc.contributor.author","Smith, Erin N."],["dc.contributor.author","Streit, Fabian"],["dc.contributor.author","Strohmaier, Jana"],["dc.contributor.author","Szelinger, Szabolcs"],["dc.contributor.author","Treutlein, Jens"],["dc.contributor.author","Witt, Stephanie H."],["dc.contributor.author","Zandi, Peter P."],["dc.contributor.author","Zhang, Peng"],["dc.contributor.author","Zöllner, Sebastian"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Falkai, Peter G."],["dc.contributor.author","Kelsoe, John R."],["dc.contributor.author","Nöthen, Markus M."],["dc.contributor.author","Rietschel, Marcella"],["dc.contributor.author","Schulze, Thomas G."],["dc.contributor.author","Malzahn, Dörthe"],["dc.date.accessioned","2019-07-09T11:50:26Z"],["dc.date.available","2019-07-09T11:50:26Z"],["dc.date.issued","2019-"],["dc.description.abstract","Genome-wide association studies of case-control status have advanced the understanding of the genetic basis of psychiatric disorders. Further progress may be gained by increasing sample size but also by new analysis strategies that advance the exploitation of existing data, especially for clinically important quantitative phenotypes. The functionally-informed efficient region-based test strategy (FIERS) introduced herein uses prior knowledge on biological function and dependence of genotypes within a powerful statistical framework with improved sensitivity and specificity for detecting consistent genetic effects across studies. As proof of concept, FIERS was used for the first genome-wide single nucleotide polymorphism (SNP)-based investigation on bipolar disorder (BD) that focuses on an important aspect of disease course, the functional outcome. FIERS identified a significantly associated locus on chromosome 15 (hg38: chr15:48965004 - 49464789 bp) with consistent effect strength between two independent studies (GAIN/TGen: European Americans, BOMA: Germans; n = 1592 BD patients in total). Protective and risk haplotypes were found on the most strongly associated SNPs. They contain a CTCF binding site (rs586758); CTCF sites are known to regulate sets of genes within a chromatin domain. The rs586758 - rs2086256 - rs1904317 haplotype is located in the promoter flanking region of the COPS2 gene, close to microRNA4716, and the EID1, SHC4, DTWD1 genes as plausible biological candidates. While implication with BD is novel, COPS2, EID1, and SHC4 are known to be relevant for neuronal differentiation and function and DTWD1 for psychopharmacological side effects. The test strategy FIERS that enabled this discovery is equally applicable for tag SNPs and sequence data."],["dc.identifier.doi","10.1016/j.euroneuro.2018.10.005"],["dc.identifier.pmid","30503783"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15939"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59772"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1873-7862"],["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","Efficient region-based test strategy uncovers genetic risk factors for functional outcome in bipolar disorder"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]