TY - THES A1 - Wagner, Martin T1 - Assoziations- und Haplotypenanalyse genetischer Veränderungen der Pannexin-Gengruppe bei Patienten mit schizophrenen Psychosen nach ICD-10 und der Klassifikation von Karl Leonhard T1 - Association and haplotype analysis of genetic changes in the pannexin gene group in patients with schizophrenic psychosis according to ICD-10 and the classification of Karl Leonhard N2 - Bestimmung von genetischen Veränderungen auf PANX 1-3 anhand von Einzelnukleotid Polymorphismen (SNP). Test auf Assoziation von Allelen und Haplotypen mit den schizophrenen Psychosen nach ICD-10 und der Klassifikation von Karl Leonhard in Form einer Fall-Kontroll-Studie mit 1163 Patienten und 479 Kontrollen. N2 - Determination of genetic changes on PANX 1-3 using single nucleotide polymorphisms (SNP). Test for association of alleles and haplotypes with schizophrenic psychosis according to ICD-10 and the classification of Karl Leonhard in the form of a case-control study with 1163 patients and 479 controls. KW - panx1 KW - panx2 KW - panx3 KW - schizophrenia KW - Pannexin KW - Schizophrenie KW - Karl Leonhard Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188512 ER - TY - JOUR A1 - van de Kerkhof, Nora WA A1 - Fekkes, Durk A1 - van der Heijden, Frank MMA A1 - Hoogendijk, Witte JG A1 - Stöber, Gerald A1 - Egger, Jos IM A1 - Verhoeven, Willem MA T1 - Cycloid psychoses in the psychosis spectrum: evidence for biochemical differences with schizophrenia JF - Neuropsychiatric Disease and Treatment N2 - Cycloid psychoses (CP) differ from schizophrenia regarding symptom profile, course, and prognosis and over many decades they were thought to be a separate entity within the psychosis spectrum. As to schizophrenia, research into the pathophysiology has focused on dopamine, brain-derived neurotrophic factor, and glutamate signaling in which, concerning the latter, the N-methyl-d-aspartate receptor plays a crucial role. The present study aims to determine whether CP can biochemically be delineated from schizophrenia. Eighty patients referred for psychotic disorders were assessed with the Comprehensive Assessment of Symptoms and History, and (both at inclusion and after 6 weeks of antipsychotic treatment) with the Positive and Negative Syndrome Scale and Clinical Global Impression. From 58 completers, 33 patients were diagnosed with schizophrenia and ten with CP according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Leonhard criteria, respectively. Fifteen patients were diagnosed with other disorders within the psychosis spectrum. At both time points, blood levels of the dopamine metabolite homovanillic acid, brain-derived neurotrophic factor, and amino acids related to glutamate neurotransmission were measured and compared with a matched control sample. Patients with CP showed a significantly better response to antipsychotic treatment as compared to patients with schizophrenia. In CP, glycine levels were elevated and tryptophan levels were lowered as compared to schizophrenia. Glutamate levels were increased in both patient groups as compared to controls. These results, showing marked differences in both treatment outcome and glutamate-related variable parameters, may point at better neuroplasticity in CP, necessitating demarcation of this subgroup within the psychosis spectrum. KW - cycloid psychoses KW - schizophrenia KW - glutamate KW - glycine KW - tryptophan KW - neuroplasticity Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166255 VL - 12 ER - TY - JOUR A1 - van de Kerkhof, Noortje W. A. A1 - van der Heijden, Frank M. M. A. A1 - Schneider, Marc K. F. A1 - Pfuhlmann, Bruno A1 - Stöber, Gerald A1 - Egger, Jos I. M. A1 - Verhoeven, Willem M. A. T1 - Cycloid psychoses: Leonhard's descriptions revisited JF - European Journal of Psychiatry N2 - Background and Objectives: Cycloid psychoses are characterized by polymorphic symptomatology with intraphasic bipolarity, a remitting and recurrent course and favourable prognosis. Perris and Brocicington (P&B) described the first set of operational criteria that were partly incorporated in ICD-10. The present study investigates psychopathological profiles according to the P&B criteria and the original descriptions by Leonhard, both against the background of the criteria from the prevailing international classification systems. Methods: Eighty patients with psychotic disorders were recruited and assessed with various psychometric instruments at baseline and after six weeks of antipsychotic treatment in order to investigate the presence of cycloid psychoses according to Leonhard (LCP) and the effect of treatment with antipsychotics. The overlap between LCP and DSM-IV Brief Psychotic Disorder (BPD), ICD Acute Polymorphic Psychotic Disorder (APP) and P&B criteria was calculated. Results: Using P&B criteria and a symptom checklist adapted from the original descriptions by Leonhard, 14 and 12 cases of cycloid psychosis were identified respectively reflecting a prevalence of 15-18%. Small though significant concordance rates were found between LCP and both DSM-BPD and ICD-APP. Concordance between LCP and P&B criteria was also significant, but modest. Conclusions: This study demonstrates that LCP can be identified in a substantial number of patients with psychotic disorders. Cycloid psychoses are not adequately covered in current classification systems and criteria. Since they are demonstrated to have a specific psychopathological profile, relapsing course and favourable prognosis, it is advocated to include these psychoses in daily differential diagnostic procedures. KW - P300 KW - endogenous psychoses KW - follow-up KW - schizophrenia KW - disorder KW - classification KW - validity KW - family Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134779 VL - 26 IS - 4 ER - TY - JOUR A1 - Van de Kerkhof, Noortje W. A. A1 - Feenstra, Ilse A1 - van der Heijden, Frank M. M. A. A1 - de Leeuw, Nicole A1 - Pfundt, Rolph A1 - Stöber, Gerald A1 - Egger, Jos I. M. A1 - Verhoeven, Willem M. A. T1 - Copy number variants in a sample of patients with psychotic disorders: is standard screening relevant for actual clinical practice? JF - Neuropsychiatric Disease and Treatment N2 - With the introduction of new genetic techniques such as genome-wide array comparative genomic hybridization, studies on the putative genetic etiology of schizophrenia have focused on the detection of copy number variants (CNVs), ie, microdeletions and/or microduplications, that are estimated to be present in up to 3% of patients with schizophrenia. In this study, out of a sample of 100 patients with psychotic disorders, 80 were investigated by array for the presence of CNVs. The assessment of the severity of psychiatric symptoms was performed using standardized instruments and ICD-10 was applied for diagnostic classification. In three patients, a submicroscopic CNV was demonstrated, one with a loss in 1q21.1 and two with a gain in 1p13.3 and 7q11.2, respectively. The association between these or other CNVs and schizophrenia or schizophrenia-like psychoses and their clinical implications still remain equivocal. While the CNV affected genes may enhance the vulnerability for psychiatric disorders via effects on neuronal architecture, these insights have not resulted in major changes in clinical practice as yet. Therefore, genome-wide array analysis should presently be restricted to those patients in whom psychotic symptoms are paired with other signs, particularly dysmorphisms and intellectual impairment. KW - microarrays KW - spectrum disorders KW - schizophrenia KW - gene KW - psychopathology KW - polymorphisms KW - microdeletion KW - perspectives KW - association KW - environment KW - copy number variants KW - 1q21 KW - 7q11.2 KW - 1p13.3 Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134769 VL - 8 ER - TY - THES A1 - Thiemeyer, Dorothea T1 - Die Konzentration von Cu/Zn- und Mn-Superoxiddismutase in humanem Hirngewebe von Patienten mit Schizophrenie beziehungsweise unipolarer Depression T1 - Cu/zn- and Mn- superoxide dismutase levels in brains of patients with schizophrenic psychosis and depressive disorder N2 - Die Bedeutung des oxidativen Stresses als ätiologischer Faktor in der Pathogenese der schizophrenen Psychosen und affektiven Störungen wird mehrfach diskutiert. In der vorliegenden Studie wurden die Konzentrationen zweier Isoenzyme der Superoxiddismutase (SOD), Cu/Zn-SOD und Mn-SOD, mittels ELISA in verschiedenen kortikalen und subkortikalen Regionen in post mortem Gehirngewebe von Patienten mit einer Erkrankung aus dem schizophrenen Formenkreis, mit einer depressiven Verstimmung und bei neuropsychiatrisch unauffälligen Individuen bestimmt. Die Ergebnisse dieser Arbeit stützen die Befunde anderer Studien, die auf eine Erhöhung des oxidativen Stresses hinweisen und eine Beteiligung freier Radikale in der Pathogenese der Schizophrenie und unipolaren Depression vermuten N2 - Impaired oxidative stress defense has been reported in patients suffering from schizophrenic psychosis or depressive disorder, indicating the involvement of free radical metabolism in the pathogenetic processes of these diseases. In this study, the concentrations of two isoenzymes of superoxide dismutase (SOD), Cu, Zn- and MnSOD, were determined with ELISA in various cortical and subcortical areas of post-mortem brain tissue from patients diagnosed with a schizophrenia spectrum disorder or depressive disorder and compared with post-mortem brain tissue from individuals without neuropsychiatric disorders. The results of this study support previous reports of impaired antioxidative defense system and suggest that increased oxidative stress plays a important role in the etiopathogenesis of major psychosis. KW - Konzentration KW - Superoxiddismutase KW - oxidativer Stress KW - Schizophrenie KW - depressive Störung KW - Superoxide dismutase KW - concentration KW - oxidative stress KW - schizophrenia KW - depressive disorder Y1 - 2006 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-20776 ER - TY - JOUR A1 - Taurines, R. A1 - Fekete, S. A1 - Preuss-Wiedenhoff, A. A1 - Warnke, A. A1 - Wewetzer, C. A1 - Plener, P. A1 - Burger, R. A1 - Gerlach, M. A1 - Romanos, M. A1 - Egberts, K. M. T1 - Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone JF - Journal of Neural Transmission N2 - Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose–concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20–60 ng/ml) is applicable for minors. In the 64 patients (aged 11–18 years) included, a positive correlation between daily dose and the active moiety (RIS\(_{am}\)) concentration was found (r\(_s\) = 0.49, p = 0.001) with variation in dose explaining 24% (r\(_s\)\(^2\) = 0.240) of the variability in serum concentrations. While the RIS\(_{am}\) concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RIS\(_{am}\) concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RIS\(_{am}\) was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions. KW - risperidone KW - children KW - serum concentration KW - schizophrenia KW - therapeutic drug monitoring KW - pharmacovigilance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324833 VL - 129 IS - 5-6 ER - TY - THES A1 - Syagaylo, Yana T1 - Strukturelle und funktionelle Untersuchung der Promotorregionen der menschlichen PAX3-, PAX6- und PAX7-Gene: Bedeutung von Polymorphismen für schizophrene Erkrankungen T1 - Structural and functional characterization of the promoter regions of the human PAX3, PAX6 and PAX7 genes: relevance of polymorphisms for schizophrenia N2 - Das Ziel dieser Arbeit war die Klärung der phänotypischen Konsequenzen struktureller Variationen in den regulatorischen Regionen einiger für psychische Erkrankungen potentiell relevanter Entwicklungsgene. Die Pax-Gene sind Mitglieder einer Familie der Transkriptionsfaktoren, die sowohl mehrere Schritte in der Embryogenese als auch Aufrechterhaltung des Differenzierungszustandes der Zellen einiger adulten Gewebe kontrollieren. Im Rahmen dieser Fragestellung wurden die Promotorregionen der menschlichen PAX3-, PAX6- und PAX7-Gene charakterisiert. Weiterhin wurden funktionelle Folgen der mit diesen Promotoren assoziierten Repeat-Polymorphismen auf die Expression dieser Gene untersucht. Schliesslich wurde die Relevanz für die psychischen Erkrankungen wie die Schizophrenie getestet. N2 - The aim of this study was the elucidation of phenotypical consequences of structural variations in regulatory regions of developmental genes that are potentially relevant for mental disease. The Pax genes are members of a family of evolutionary conserved transcription factors, which control several steps in the embryogenesis as well as maintain the differentiation status of cells in adult tissues. In this context the promoter regions of the human PAX3, PAX6 and PAX7 genes were characterized. Therefore, functional effects of the polymorphic repetitive elements in the gene promoter regions on the expression of these genes were examined. Finally, the relevance for the psychiatric diseases like schizophrenia was tested. KW - Schizophrenie KW - Transkriptionsfaktor KW - Genanalyse KW - Promotor KW - PAX-Gene KW - Promotor KW - Promotorpolymorphismus KW - Schizophrenieerkrankung KW - PAX genes KW - promoter KW - promoter polymorphism KW - schizophrenia Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-5459 ER - TY - JOUR A1 - Stöber, Gerald A1 - Franzek, E. A1 - Beckmann, H. T1 - The role of maternal infectious diseases during pregnancy in the etiology of schizophrenia in offspring N2 - In 55 chronic schizophrenics, the occurrence of infectious diseases during their mothers' pregnancies was investigated. Different psychiatrie diagnostic systems were compared. Infections were reported by the mothers of familial and sporadic DSM I1I-R schizophrenics in equal proportion. However, applying Leonhard's classification, the frequency of infections was found to be significantly increased in 'systematic' schizophrenia (mainly exogenously induced in the view of Leonhard) compared to 'unsystematic' schizophrenia (mainly genetically determined according to Leonhard's findings). Most of the infections occurred during the second trimester (nine out of 13). Thus, in the 'systematic' forms of schizophrenia (low genetic loading), maternal infections in this crucial period of neurodevelopment would appear to be important causative factors in the cytoarchitectural deviance detected in the central nervous system of schizophrenics. KW - Psychiatrie KW - maternal infection KW - pregnancy KW - schizophrenia KW - familial-sporadic concept KW - Leonhard classification Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82216 ER - TY - JOUR A1 - Stöber, Gerald A1 - Franzek, E. A1 - Beckmann, H. T1 - Obstetric complications in distinct Schizophrenie subgroups N2 - In 55 chronic DSM I11 -R schi zophre nics the occurrence of obstetr ic complica ti ons (OCs) was investigated us ing the famili al/sporael ic strategy and Leonhard's unsystemati c/systematic distin ction. The overa ll frequency and severity of OCs elid not differ be tween patie nts anel controls. A sub-sample of patients, whose genetic ri sk was supposed to be high in both class ification systems (d iagnos is 01' unsystematic anel fa mili al sc hizophre ni a), had s igni ficantly fewer OCs than controls on the Lewis anel Murray scale (P < 0.05). With reference to previous reports of inc reased morta lity rates in the offspring of schizop hre nics, high genetic risk and addition al perinatal stressors may in crease perin atal mortality. In contrast, pat ie nts whose genetic ri sk was sllpposed to be low in both systems (di agnos is of systematic and sporadic sc hizophrenia) showed a trend to an increased freqllency of OCs in the Fuchs scale. In the context of the recently reported highl y signi ficantly increased rate of matern al infections dllring midgestation in these pati e nts, it was supposed th at perin atal complications may be of so me ae tio logical importance in sc hizophrenics with low genetic ri sk. KW - Psychiatrie KW - obstetric complications KW - schizophrenia KW - famiIiaI ·sporadic concept KW - Leonhard cIassification Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82223 ER - TY - JOUR A1 - Stepniak, Beata A1 - Kästner, Anne A1 - Poggi, Giulia A1 - Mitjans, Marina A1 - Begemann, Martin A1 - Hartmann, Annette A1 - Van der Auwera, Sandra A1 - Sananbenesi, Farahnaz A1 - Krüger-Burg, Dilja A1 - Matuszko, Gabriela A1 - Brosi, Cornelia A1 - Homuth, Georg A1 - Völzke, Henry A1 - Benseler, Fritz A1 - Bagni, Claudia A1 - Fischer, Utz A1 - Dityatev, Alexander A1 - Grabe, Hans-Jörgen A1 - Rujescu, Dan A1 - Fischer, Andre A1 - Ehrenreich, Hannelore T1 - Accumulated common variants in the broader fragile X gene family modulate autistic phenotypes JF - EMBO Molecular Medicine N2 - 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. KW - permutation KW - miR-181 KW - PGAS KW - FXR2 KW - FXR1 KW - FMR2 KW - FMR1 KW - identification KW - protein KW - fraxe mental retardation KW - CGG repeat KW - CPG Island KW - schizophrenia KW - expression KW - males Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136893 VL - 7 IS - 12 ER -