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Scharfetter

Fakultäten » Medizinische Fakultät » Psychiatrische Universitätsklinik » Psychiatrie, Psychotherapie und Psychosomatik, Klinik für » Prof. Dr. Daniel Hell (emeritiert) » Scharfetter

Completed research project

Title / Titel Oligogenic Approaches to Ethnicity-Independent Vulnerability in Schizophrenia
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung The functional psychoses “schizophrenia”, “schizoaffective disorders”, and “bipolar illness” are complex diseases with a strong genetic component that does not follow simple Mendelian or near Mendelian modes of inheritance. The clinical evidence that finally led to their clinical differentiation into distinct diagnostic entities has long been regarded as also constituting etiologic entities. Yet an increasing number of studies carried out over the past years has challenged this view, suggesting that etiological differences might be of a quantitative rather than qualitative nature. Standard linkage methods enable the localization of genes coding for traits influenced by a few major genes, but do not support analyses of locus configurations, and do not take inter-locus dependencies into account. To overcome these difficulties, we have introduced the concept of genetic vector spaces, along with a genetic similarity function that simultaneously evaluates sets of 5-35 genomic loci while allowing for nonlinear interactions between loci. This method of approach enables one to compare the distribution of parent-offspring similarities —with a priori mean “0.5”, irrespective of the affection status of parents and offspring— with the distribution of sib-sib similarities, whose means are expected to deviate from “0.5” in affected sib pairs if the region of interest contains markers close to disease-related or protecting genes (“multivariate linkage” paradigm). Using the genetic vector space method along with a multiplex nuclear family design, our analyses yielded a “resilience”-like configuration of vulnerability and protection loci that turned out to be ethnicity-independent, when comparing Afro-Americans with European-Americans, and to be similarly involved in the pathogenesis of schizophrenia and bipolar illness.
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Publications / Publikationen
Stassen HH, Bridler R, Hell D, Weisbrod M, Scharfetter C: Ethnicity-independent genetic basis of functional psychoses. A Genotype-to-phenotype approach. Am J Med Genetics 2004; 124: 101-112

Stassen HH, Scharfetter C: Ethnische Zugehörigkeit und Vulnerabilität am Beispiel der Affektkrankheiten und Schizophrenien. Die Psychiatrie 2005; 2: 85-95

Stassen HH, Angst J, Scharfetter C: Genetik affektiver Störungen —der quantitative Ansatz syndrom-orientierter Modelle. In: M. Leuzinger-Bohleber, S. Hau, H. Deserno (hsg): Depression –Pluralismus in Praxis und Forschung, Vandenhoeck & Ruprecht, Göttingen, 2005, pp. 219-257

Stassen HH, Scharfetter C, Angst J: Functional Psychoses —Molecular-genetic Evidence for a Continuum. In: A. Marneros and H.S. Akiskal (eds) The overlap of affective and schizophrenic spectra. Cambridge University Press 2006, pp. 55-78

Berger M, Stassen HH, Köhler K, Krane V, Mönks D, Wanner C, Hoffmann K, Hoffmann MM, Zimmer M, Bickeböller H, Lindner TH: Hidden population substructures in an apparently homogeneous population bias association studies. Eur J Hum Genetics 2006; 14: 236-244

Stassen HH, Scharfetter C: Vulnerability, resilience and response to psychotropic drugs: sheared genetic factors? Am J Med Genetics 2006; 141: 707-708

Stassen HH, Szegedi A, Scharfetter C: Modeling Activation of Inflammatory Response System. A Molecular-Genetic Neural Network Analysis. BMC Proceedings 2007, 1 (Suppl 1): S61

Stassen HH, Angst J, Hell D, Scharfetter C, Szegedi A: Is there a common resilience mechanism underlying antidepressant drug response? Evidence from 2848 patients. J Clin Psychiatry 2007; 68(8): 1195-1205

Stassen HH, Angst J, Scharfetter C, Szegedi A: What lets patients under antidepressants get stuck in their recovery after initial improvement? Eur Neuropsychopharmacol. 2007; 17 (Suppl. 4): S344-345

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Keywords / Suchbegriffe schizophrenia, functional psychoses, complex disorders, molecular genetics, genetic diversity, population admixture, epistasis
Project leadership and contacts /
Projektleitung und Kontakte
Prof. Dr. Christian Scharfetter (Project Leader) christian.scharfetter@bluewin.ch
Prof. Dr. Hans H. Stassen k454910@bli.uzh.ch
PD Dr. Matthias Weisbrod  
Dr. René Bridler  
Funding source(s) /
Unterstützt durch
SNF (Personen- und Projektförderung), Other Public Sources (e.g. Federal or Cantonal Agencies)
NIMH
In collaboration with /
In Zusammenarbeit mit
PD Dr. M. Weisbrod
Psychiatric University Hospital
Section Experimental Psychopathology
Voßstraße 4
D-69115 Heidelberg
Germany
Dr. Katrin Hoffmann
Max Delbruck Center for Molecular Medicine
Robert Roessle Str. 10
D-13092 Berlin
Germany
NIMH Human Genetics Initiative
National Institute of Mental Health
6001 Executive Blvd
Bethesda, MD 20892-9643
United States
Duration of Project / Projektdauer Apr 2004 to Apr 2010