Stepniak, Beata

[["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","1143"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Molecular Psychiatry"],["dc.bibliographiccitation.lastpage","1149"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Hammer, Christian"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Sirén, Anna-Leena"],["dc.contributor.author","Pardo, Luis A."],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Mohd Jofrry, Sue"],["dc.contributor.author","Gurvich, Artem"],["dc.contributor.author","Jensen, Niels"],["dc.contributor.author","Ostmeier, Katrin"],["dc.contributor.author","Lühder, F."],["dc.contributor.author","Probst, Christian"],["dc.contributor.author","Martens, Henrik"],["dc.contributor.author","Gillis, M."],["dc.contributor.author","Saher, Gesine"],["dc.contributor.author","Assogna, F."],["dc.contributor.author","Spalletta, Gianfranco"],["dc.contributor.author","Stöcker, W."],["dc.contributor.author","Schulz, Thomas F."],["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","2014"],["dc.description.abstract","In 2007, a multifaceted syndrome, associated with anti-NMDA receptor autoantibodies (NMDAR-AB) of immunoglobulin-G isotype, has been described, which variably consists of psychosis, epilepsy, cognitive decline and extrapyramidal symptoms. Prevalence and significance of NMDAR-AB in complex neuropsychiatric disease versus health, however, have remained unclear. We tested sera of 2817 subjects (1325 healthy, 1081 schizophrenic, 263 Parkinson and 148 affective-disorder subjects) for presence of NMDAR-AB, conducted a genome-wide genetic association study, comparing AB carriers versus non-carriers, and assessed their influenza AB status. For mechanistic insight and documentation of AB functionality, in vivo experiments involving mice with deficient blood-brain barrier (ApoE(-/-)) and in vitro endocytosis assays in primary cortical neurons were performed. In 10.5% of subjects, NMDAR-AB (NR1 subunit) of any immunoglobulin isotype were detected, with no difference in seroprevalence, titer or in vitro functionality between patients and healthy controls. Administration of extracted human serum to mice influenced basal and MK-801-induced activity in the open field only in ApoE(-/-) mice injected with NMDAR-AB-positive serum but not in respective controls. Seropositive schizophrenic patients with a history of neurotrauma or birth complications, indicating an at least temporarily compromised blood-brain barrier, had more neurological abnormalities than seronegative patients with comparable history. A common genetic variant (rs524991, P=6.15E-08) as well as past influenza A (P=0.024) or B (P=0.006) infection were identified as predisposing factors for NMDAR-AB seropositivity. The >10% overall seroprevalence of NMDAR-AB of both healthy individuals and patients is unexpectedly high. Clinical significance, however, apparently depends on association with past or present perturbations of blood-brain barrier function."],["dc.identifier.doi","10.1038/mp.2013.110"],["dc.identifier.gro","3150565"],["dc.identifier.pmid","23999527"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7339"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","115"],["dc.bibliographiccitation.journal","BMC Psychiatry"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Kästner, A."],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Michel, Tanja Maria"],["dc.contributor.author","Everts, Sarah"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Bach, Christiane"],["dc.contributor.author","Becker, Joachim"],["dc.contributor.author","Banaschewski, Tobias"],["dc.contributor.author","Dose, Matthias"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-08-25T10:15:13Z"],["dc.date.available","2017-08-25T10:15:13Z"],["dc.date.issued","2015"],["dc.description.abstract","BACKGROUND: Behavioral phenotypical continua from health to disease suggest common underlying mechanisms with quantitative rather than qualitative differences. Until recently, autism spectrum disorders and schizophrenia were considered distinct nosologic entities. However, emerging evidence contributes to the blurring of symptomatic and genetic boundaries between these conditions. The present study aimed at quantifying behavioral phenotypes shared by autism spectrum disorders and schizophrenia to prepare the ground for biological pathway analyses.; METHODS: Specific items of the Positive and Negative Syndrome Scale were employed and summed up to form a dimensional autism severity score (PAUSS). The score was created in a schizophrenia sample (N=1156) and validated in adult high-functioning autism spectrum disorder (ASD) patients (N=165). To this end, the Autism Diagnostic Observation Schedule (ADOS), the Autism (AQ) and Empathy Quotient (EQ) self-rating questionnaires were applied back to back with the newly developed PAUSS.; RESULTS: PAUSS differentiated between ASD, schizophrenia and a disease-control sample and substantially correlated with the Autism Diagnostic Observation Schedule. Patients with ADOS scores ≥12 obtained highest, those with scores <7 lowest PAUSS values. AQ and EQ were not found to vary dependent on ADOS diagnosis. ROC curves for ADOS and PAUSS resulted in AuC values of 0.9 and 0.8, whereas AQ and EQ performed at chance level in the prediction of ASD.; CONCLUSIONS: This work underscores the convergence of schizophrenia negative symptoms and autistic phenotypes. PAUSS evolved as a measure capturing the continuous nature of autistic behaviors. The definition of extreme-groups based on the dimensional PAUSS may permit future investigations of genetic constellations modulating autistic phenotypes."],["dc.format.extent","12"],["dc.identifier.doi","10.1186/s12888-015-0494-x"],["dc.identifier.gro","3151226"],["dc.identifier.pmid","25968177"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12530"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8006"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-07-25"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1471-244X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Autism spectrum disorders; Positive and negative syndrome scale; Autism diagnostic observation schedule; Diagnostics, Autism quotient; Empathy quotient; Adults"],["dc.title","Autism beyond diagnostic categories: characterization of autistic phenotypes 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","135"],["dc.bibliographiccitation.journal","Molecular Medicine"],["dc.bibliographiccitation.lastpage","148"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Man, Kwun-nok M"],["dc.contributor.author","Müller-Ribbe, Katja"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Ju, Anes"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Gurvich, Artem"],["dc.contributor.author","Shin, Yong"],["dc.contributor.author","Augustin, Iris"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:37Z"],["dc.date.available","2017-09-07T11:46:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Anxiety disorders and substance abuse, including benzodiazepine use disorder, frequently occur together. Unfortunately, treatment of anxiety disorders still includes benzodiazepines, and patients with an existing comorbid benzodiazepine use disorder or a genetic susceptibility for benzodiazepine use disorder may be at risk of adverse treatment outcomes. The identification of genetic predictors for anxiety disorders, and especially for benzodiazepine use disorder, could aid the selection of the best treatment option and improve clinical outcomes. The brain-specific angiogenesis inhibitor I-associated protein 3 (Baiap3) is a member of the mammalian uncoordinated 13 (Munc13) protein family of synaptic regulators of neurotransmitter exocytosis, with a striking expression pattern in amygdalae, hypothalamus and periaqueductal gray. Deletion of Baiap3 in mice leads to enhanced seizure propensity and increased anxiety, with the latter being more pronounced in female than in male animals. We hypothesized that genetic variation in human BAIAP3 may also be associated with anxiety. By using a phenotype-based genetic association study, we identified two human BAIAP3 single-nucleotide polymorphism risk genotypes (AA for rs2235632, TT for rs1132358) that show a significant association with anxiety in women and, surprisingly, with benzodiazepine abuse in men. Returning to mice, we found that male, but not female, Baiap3 knockout (KO) mice develop tolerance to diazepam more quickly than control animals. Analysis of cultured Baiap3 KO hypothalamus slices revealed an increase in basal network activity and an altered response to diazepam withdrawal. Thus, Baiap3/BAIAP3 is gender specifically associated with anxiety and benzodiazepine use disorder, and the analysis of Baiap3/BAIAP3-related functions may help elucidate mechanisms underlying the development of both disorders."],["dc.identifier.doi","10.2119/molmed.2013.00033"],["dc.identifier.gro","3150563"],["dc.identifier.pmid","23698091"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7337"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Genetic Markers of a Munc13 Protein Family Member, BAIAP3, Are Gender Specifically Associated with Anxiety and Benzodiazepine Abuse in Mice and Humans"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e254"],["dc.bibliographiccitation.journal","Translational Psychiatry"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Klugmann, M."],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Hammer, Christian"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Monasterio-Schrader, P. D."],["dc.contributor.author","Strenzke, N."],["dc.contributor.author","Flügge, G."],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Pawlak, R."],["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","2013"],["dc.description.abstract","Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3'untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia."],["dc.format.extent","12"],["dc.identifier.doi","10.1038/tp.2013.28"],["dc.identifier.gro","3150562"],["dc.identifier.pmid","23632458"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10616"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7336"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.subject","chromosome 4; GPM6A; human pedigree; miR124; mouse mutant; panic disorder"],["dc.title","A single gene defect causing claustrophobia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1029"],["dc.bibliographiccitation.journal","Molecular Medicine"],["dc.bibliographiccitation.lastpage","1040"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Sargin, Derya"],["dc.contributor.author","Schwitulla, Judith"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Giegling, Ina"],["dc.contributor.author","Miskowiak, Kamilla W."],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Hannke, Kathrin"],["dc.contributor.author","Ramin, Anna"],["dc.contributor.author","Heinrich, Ralf"],["dc.contributor.author","Gefeller, Olaf"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Rujescu, Dan"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:36Z"],["dc.date.available","2017-09-07T11:46:36Z"],["dc.date.issued","2012"],["dc.description.abstract","Erythropoietin (EPO) improves cognitive performance in clinical studies and rodent experiments. We hypothesized that an intrinsicrole of EPO for cognition exists, with particular relevance in situations of cognitive decline, which is reflected by associations ofEPO and EPO receptor (EPOR) genotypes with cognitive functions. To prove this hypothesis, schizophrenic patients (N > 1000) weregenotyped for 5′ upstream–located gene variants, EPO SNP rs1617640 (T/G) and EPOR STR(GA)n. Associations of these variants wereobtained for cognitive processing speed, fine motor skills and short-term memory readouts, with one particular combination ofgenotypes superior to all others (p < 0.0001). In an independent healthy control sample (N > 800), these associations were confirmed.A matching preclinical study with mice demonstrated cognitive processing speed and memory enhanced upon transgenicexpression of constitutively active EPOR in pyramidal neurons of cortex and hippocampus. We thus predicted that thehuman genotypes associated with better cognition would reflect gain-of-function effects. Indeed, reporter gene assays and quantitativetranscriptional analysis of peripheral blood mononuclear cells showed genotype-dependent EPO/EPOR expression differences.Together, these findings reveal a role of endogenous EPO/EPOR for cognition, at least in schizophrenic patients."],["dc.identifier.doi","10.2119/molmed.2012.00190"],["dc.identifier.gro","3150561"],["dc.identifier.pmid","22669473"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7335"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Common variants of the genes encoding erythropoietin and its receptor modulate cognitive performance in schizophrenia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","82"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","94"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Dahm, Liane"],["dc.contributor.author","Ott, Christoph"],["dc.contributor.author","Steiner, Johann"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Teegen, Bianca"],["dc.contributor.author","Saschenbrecker, Sandra"],["dc.contributor.author","Hammer, Christian"],["dc.contributor.author","Borowski, Kathrin"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Lemke, Sandra"],["dc.contributor.author","Rentzsch, Kristin"],["dc.contributor.author","Probst, Christian"],["dc.contributor.author","Martens, Henrik"],["dc.contributor.author","Wienands, Jürgen"],["dc.contributor.author","Spalletta, Gianfranco"],["dc.contributor.author","Weißenborn, Karin"],["dc.contributor.author","Stöcker, Winfried"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:34Z"],["dc.date.available","2017-09-07T11:46:34Z"],["dc.date.issued","2014"],["dc.description.abstract","ObjectiveWe previously reported an unexpectedly high seroprevalence (∼10%) of N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1) autoantibodies (AB) in healthy and neuropsychiatrically ill subjects (N = 2,817). This finding challenges an unambiguous causal relationship of serum AB with brain disease. To test whether similar results would be obtained for other brain antigen-directed AB previously connected with pathological conditions, we systematically screened serum samples of 4,236 individuals.MethodsSerum samples of healthy (n = 1,703) versus neuropsychiatrically ill subjects (schizophrenia, affective disorders, stroke, Parkinson disease, amyotrophic lateral sclerosis, personality disorder; total n = 2,533) were tested. For analysis based on indirect immunofluorescence, we used biochip mosaics of frozen brain sections (rat, monkey) and transfected HEK293 cells expressing respective recombinant target antigens.ResultsSeroprevalence of all screened AB was comparable in healthy and ill individuals. None of them, however, reached the abundance of NMDAR1 AB (again ∼10%; immunoglobulin [Ig] G ∼1%). Appreciable frequency was noted for AB against amphiphysin (2.0%), ARHGAP26 (1.3%), CASPR2 (0.9%), MOG (0.8%), GAD65 (0.5%), Ma2 (0.5%), Yo (0.4%), and Ma1 (0.4%), with titers and Ig class distribution similar among groups. All other AB were found in ≤0.1% of individuals (anti–AMPAR-1/2, AQP4, CV2, Tr/DNER, DPPX-IF1, GABAR-B1/B2, GAD67, GLRA1b, GRM1, GRM5, Hu, LGl1, recoverin, Ri, ZIC4). The predominant Ig class depended on antigen location, with intracellular epitopes predisposing to IgG (chi-square = 218.91, p = 2.8 × 10−48).InterpretationTo conclude, the brain antigen-directed AB tested here are comparably detectable in healthy subjects and the disease groups studied here, thus questioning an upfront pathological role of these serum AB."],["dc.identifier.doi","10.1002/ana.24189"],["dc.identifier.gro","3150539"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7312"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Seroprevalence of autoantibodies against brain antigens in health and disease"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","444"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","The Lancet Psychiatry"],["dc.bibliographiccitation.lastpage","453"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Ramin, Anna"],["dc.contributor.author","Everts, Sarah"],["dc.contributor.author","Hennig, Lena"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:34Z"],["dc.date.available","2017-09-07T11:46:34Z"],["dc.date.issued","2014"],["dc.description.abstract","BackgroundSchizophrenia is caused by a combination of genetic and environmental factors, as first evidenced by twin studies. Extensive efforts have been made to identify the genetic roots of schizophrenia, including large genome-wide association studies, but these yielded very small effect sizes for individual markers. In this study, we aimed to assess the relative contribution of genome-wide association study-derived genetic versus environmental risk factors to crucial determinants of schizophrenia severity: disease onset, disease severity, and socioeconomic measures.MethodsIn this parallel analysis, we studied 750 male patients from the Göttingen Research Association for Schizophrenia (GRAS) dataset (Germany) with schizophrenia for whom both genome-wide coverage of single-nucleotide polymorphisms and deep clinical phenotyping data were available. Specifically, we investigated the potential effect of schizophrenia risk alleles as identified in the most recent large genome-wide association study versus the effects of environmental hazards (ie, perinatal brain insults, cannabis use, neurotrauma, psychotrauma, urbanicity, and migration), alone and upon accumulation, on age at disease onset, age at prodrome, symptom expression, and socioeconomic parameters.FindingsIn this study, we could show that frequent environmental factors become a major risk for early schizophrenia onset when accumulated (prodrome begins up to 9 years earlier; p=2·9×10−10). In particular, cannabis use—an avoidable environmental risk factor—is highly significantly associated with earlier age at prodrome (p=3·8×10−20). By contrast, polygenic genome-wide association study risk scores did not have any detectable effects on schizophrenia phenotypes.InterpretationThese findings should be translated to preventive measures to reduce environmental risk factors, since age at onset of schizophrenia is a crucial determinant of an affected individual's fate and the total socioeconomic cost of the illness."],["dc.identifier.doi","10.1016/S2215-0366(14)70379-7"],["dc.identifier.gro","3150540"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7313"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Accumulated environmental risk determining age at schizophrenia onset: a deep phenotyping-based study"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","662"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","684"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Hammer, Christian"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Dahm, Liane"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Bodda, Chiranjeevi"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Giegling, Ina"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Castillo Venzor, Aracely"],["dc.contributor.author","Konte, Bettina"],["dc.contributor.author","Erbaba, Begun"],["dc.contributor.author","Hartmann, Annette M."],["dc.contributor.author","Tarami, Asieh"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Rujescu, Dan"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:35Z"],["dc.date.available","2017-09-07T11:46:35Z"],["dc.date.issued","2014"],["dc.description.abstract","The X-chromosomal MECP2/Mecp2 gene encodes methyl-CpG-binding protein 2, a transcriptional activator and repressor regulating many other genes. We discovered in male FVB/N mice that mild (~50%) transgenic overexpression of Mecp2 enhances aggression. Surprisingly, when the same transgene was expressed in C57BL/6N mice, transgenics showed reduced aggression and social interaction. This suggests that Mecp2 modulates aggressive social behavior. To test this hypothesis in humans, we performed a phenotype-based genetic association study (PGAS) in >1000 schizophrenic individuals. We found MECP2 SNPs rs2239464 (G/A) and rs2734647 (C/T; 3'UTR) associated with aggression, with the G and C carriers, respectively, being more aggressive. This finding was replicated in an independent schizophrenia cohort. Allele-specific MECP2 mRNA expression differs in peripheral blood mononuclear cells by ~50% (rs2734647: C > T). Notably, the brain-expressed, species-conserved miR-511 binds to MECP2 3'UTR only in T carriers, thereby suppressing gene expression. To conclude, subtle MECP2/Mecp2 expression alterations impact aggression. While the mouse data provides evidence of an interaction between genetic background and mild Mecp2 overexpression, the human data convey means by which genetic variation affects MECP2 expression and behavior."],["dc.identifier.doi","10.1002/emmm.201303744"],["dc.identifier.gro","3150551"],["dc.identifier.pmid","24648499"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11691"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7325"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Mild expression differences of MECP2 influencing aggressive social behavior"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]