Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-25T19:40:32.897Z Has data issue: false hasContentIssue false
  • English
  • Français

A roadmap to disentangle the molecular etiology of schizophrenia

Published online by Cambridge University Press:  16 April 2020

Peter Falkai ,
Owen Mike ,
Myin-Germeys Inez ,
Harrison Paul ,
Bilkei-Gorzo Andras ,
Frangou Sophia  and
MEOS Consortium
Peter Falkai*
Affiliation:
Department of Psychiatry and Psychotherapy, University of Goettingen, Von-Siebold-Strasse 5, 37075Goettingen, Germany
Owen Mike
Affiliation:
Department of Psychological Medicine, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, CardiffCF14 4XN, UK
Myin-Germeys Inez
Affiliation:
Deptment of Psychiatry and Neuropsychology, Maastricht University, PO BOX 616 (location DOT10), 6200MD Maastricht, The Netherlands
Harrison Paul
Affiliation:
Neurosciences Building, University Department of Psychiatry Warneford Hospital, OxfordOX3 7JX, UK
Bilkei-Gorzo Andras
Affiliation:
Department of Psychiatry, University of Bonn, Sigmund-Freud-Street 25, 53127Bonn, Germany
Frangou Sophia
Affiliation:
Section of Neurobiology of Psychosis, Institute of Psychiatry, De Crespigny Park, LondonSE5 8AF, UK
*
∗Corresponding author. Tel.: +49 (0) 551 39 6601; fax: +49 (0) 551 39 9337. E-mail address: pfalkai@gwdg.de (P. Falkai).
Get access

Abstract

Schizophrenia is a severe mental disorder striking mainly young adults and leading to life-long disability in a substantial portion of the sufferers. On the other hand, substantial knowledge about its etiology and pathogenesis is still lacking. Therefore the European Science Foundation (ESF) sponsored a meeting of a panel of European experts on schizophrenia research to discuss the state of art and future perspectives of key topics in this area. The fields covered genetics, epidemiology, animal models, molecular neuropathology and imaging. This was a first step to establish a network of European groups dedicated to Schizophrenia research. The coming calls of the frame work program will be used to strengthen this network in order to achieve substantial progress in understanding and treating this devastating illness.

Keywords

Imaging, molecular neuropathologyImaging and bipolar disordersAnimal modelsGene–environment interactionMolecular neuropathology, function of susceptibility genesImagingGenetic of psychiatric illnessesGenetics, function of susceptibility genesImaging and early recognitionEpidemiologyGeneticsDevelopment of pharmacotropic agents from target proteinsLarge-scale clinical studies on schizophrenia
Type
Original article
Information
European Psychiatry , Volume 23 , Issue 4 , June 2008 , pp. 224 - 232
Copyright
Copyright © European Psychiatric Association 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Addington, A.M.Gornick, M.Duckworth, J.Sporn, A.Gogtay, N.Bobb, A.et al.GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. Mol PsychiatryJun 2005;10(6):581–588.CrossRefGoogle Scholar
Addington, A.M.Gornick, M.C.Shaw, P.Seal, J.Gogtay, N.Greenstein, D.et al.Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories. Mol Psychiatry 2007 Feb;12(2):195–205.CrossRefGoogle ScholarPubMed
Cardno, A.G.Gottesman, IITwin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet 2000;97(1):12–17.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
Carlsson, A.The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1988;1(3):179–186.CrossRefGoogle ScholarPubMed
Cougnard, A.Goumilloux, R.Monello, F.Verdoux, H.Time between schizophrenia onset and first request for disability status in France and associated patient characteristics. Psychiatr Serv 2007 Nov;58(11):1427–1432.CrossRefGoogle ScholarPubMed
Craddock, N.O'Donovan, M.C.Owen, M.J.Phenotypic and genetic complexity of psychosis. Invited commentary on… schizophrenia: a common disease caused by multiple rare alleles. Br J Psychiatry 2007;190:200–203.CrossRefGoogle Scholar
Frangou, S.Dakhil, N.Landau, S.Kumari, V.Fronto-temporal function may distinguish bipolar disorder from schizophrenia. Bipolar Disord 2006;8(1):47–55.CrossRefGoogle ScholarPubMed
Greenstein, D.Lerch, J.Shaw, P.Clasen, L.Giedd, J.Gochman, P.et al.Childhood onset schizophrenia: cortical brain abnormalities as young adults. J Child Psychol Psychiatry 2006;47(10):1003–1012.CrossRefGoogle ScholarPubMed
Harrison, P.J.The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 1999;122(Pt 4):593–624.CrossRefGoogle ScholarPubMed
Harrison, P.J.Law, A.J.Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol Psychiatry 2006 Jul 15;60(2):132–140.CrossRefGoogle ScholarPubMed
van Haren, N.E.Pol, H.E.Schnack, H.G.Cahn, W.Brans, R.Carati, I.et al.Progressive brain volume loss in schizophrenia over the course of the illness: evidence of maturational abnormalities in early adulthood. Biol Psychiatry 2007;63(1):106–113.CrossRefGoogle ScholarPubMed
Honea, R.Crow, T.J.Passingham, D.Mackay, C.E.Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am J Psychiatry 2005;162(12):2233–2245.CrossRefGoogle ScholarPubMed
Kyriakopoulos, M.Vyas, N.S.Barker, G.J.Chitnis, X.A.Frangou, S.A diffusion tensor imaging study of white matter in early-onset schizophrenia. Biol Psychiatry 2007 Jul 27; [epub ahead of print]Google ScholarPubMed
Law, A.J.Lipska, B.K.Weickert, C.S.Hyde, T.M.Straub, R.E.Hashimoto, R.et al.Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5′ SNPs associated with the disease. Proc Natl Acad Sci U S A 2006;103(17):6747–6752.CrossRefGoogle ScholarPubMed
McClellan, J.M.Susser, E.King, M.C.Schizophrenia: a common disease caused by multiple rare alleles. Br J Psychiatry 2007;190:194–199.CrossRefGoogle ScholarPubMed
McIntosh, A.M.Moorhead, T.W.Job, D.Lymer, G.K.Muñoz Maniega, S.McKirdy, J.et al.The effects of a neuregulin 1 variant on white matter density and integrity. Mol Psychiatry 2007 Oct 9 [epub ahead of print]Google ScholarPubMed
Millar, J.K.Wilson-Annan, J.C.Anderson, S.Christie, S.Taylor, M.S.Semple, C.A.et al.Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet 2000;9(9):1415–1423.CrossRefGoogle ScholarPubMed
Nugent, T.F. IIIHerman, D.H.Ordonez, A.Greenstein, D.Hayashi, K.M.Lenane, M.et al.Dynamic mapping of hippocampal development in childhood onset schizophrenia. Schizophr Res 2007;90(1–3):62–70.CrossRefGoogle ScholarPubMed
Olesen, J.Baker, M.G.Freund, T.di Luca, M.Mendlewicz, J.Ragan, I.et al.Consensus document on European brain research. J Neurol Neurosurg Psychiatry 2006 Feb 17; [epub ahead of print]Google ScholarPubMed
Owen, M.J.Craddock, N.Jablensky, A.The genetic deconstruction of psychosis. Schizophr Bull 2007;33(4):905–911.CrossRefGoogle Scholar
Pantelis, C.Velakoulis, D.McGorry, P.D.Wood, S.J.Suckling, J.Phillips, L.J.et al.Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 2003;361(9354):281–288.CrossRefGoogle ScholarPubMed
Perala, J.Suvisaari, J.Saarni, S.I.Kuoppasalmi, K.Isometsä, E.Pirkola, S.et al.Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry 2007;64(1):19–28.CrossRefGoogle Scholar
Peters, G.Neuropathologie und Psychiatrie. In: Gruhle, H.W. editor. Psychiatrie der Gegenwart. Band I Berlin: Springer; 1967. p. 298–305.Google Scholar
Petretto, E.Liu, E.T.Aitman, T.J.A gene harvest revealing the archeology and complexity of human disease. Nat Genet 2007;39(11):1299–1301.CrossRefGoogle ScholarPubMed
Risch, N.Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 1990;46(2):222–228.Google ScholarPubMed
Schmitt, A.Bauer, M.Heinsen, H.Feiden, W.Consortium of Brainnet Europe II Falkai, P.et al.How a neuropsychiatric brain bank should be run: a consensus paper of Brainnet Europe II. J Neural Transm 2006;114(5):527–537.CrossRefGoogle Scholar
Sei, Y.Ren-Patterson, R.Li, Z.Tunbridge, E.M.Egan, M.F.Kolachana, B.S.et al.Neuregulin1-induced cell migration is impaired in schizophrenia: association with neuregulin1 and catechol-o-methyltransferase gene polymorphisms. Mol Psychiatry 2007;12(10):946–957.CrossRefGoogle ScholarPubMed
Spauwen, J.Krabbendam, L.Lieb, R.Wittchen, H.U.van Os, J.Sex differences in psychosis: normal or pathological?. Schizophr Res 2003 Jul 1;62(1–2):45–49.CrossRefGoogle ScholarPubMed
Stefansson, H.Sigurdsson, E.Steinthorsdottir, V.Bjornsdottir, S.Sigmundsson, T.Ghosh, S.et al.Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 2002;71(4):877–892.CrossRefGoogle Scholar
Sullivan, P.F.Kendler, K.S.Neale, M.C.Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003;60(12):1187–1192.CrossRefGoogle ScholarPubMed
Sullivan, P.F.The genetics of schizophrenia. PLoS Med 2005;2(7):e212.CrossRefGoogle ScholarPubMed
Sullivan, P.F.Neale, B.M.Neale, M.C.van den Oord, E.Kendler, K.S.Multipoint and single point non-parametric linkage analysis with imperfect data. Am J Med Genet B Neuropsychiatr Genet 2003 Aug 15;121(1):89–94.CrossRefGoogle Scholar
Stefanis, N.C.Trikalinos, T.A.Avramopoulos, D.Smyrnis, N.Evdokimidis, I.Ntzani, E.E.et al.Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level. Biol Psychiatry 2007;62(7):784–792.CrossRefGoogle ScholarPubMed
Straub, R.E.Jiang, Y.MacLean, C.J.Ma, Y.Webb, B.T.Myakishev, M.V.et al.Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am J Hum Genet 2002;71(2):337–348.CrossRefGoogle ScholarPubMed
Thompson, P.M.Vidal, C.Giedd, J.N.Gochman, P.Blumenthal, J.Nicolson, R.et al.Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci U S A 2001;98(20):11650–11655.CrossRefGoogle ScholarPubMed
Todd, J.A.Statistical false positive or true disease pathway?. Nat Genet 2006;38(7):731–733.CrossRefGoogle ScholarPubMed
Walters, J.T.Owen, M.J.Endophenotypes in psychiatric genetics. Mol Psychiatry 2007;12(10):886–890.CrossRefGoogle ScholarPubMed
Wang, W.Y.Barratt, B.J.Clayton, D.G.Todd, J.A.Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet 2005;6(2):109–118.CrossRefGoogle ScholarPubMed
Wellcome Trust Case Control Consortium Genome-wide association study of 14,000 cases of seven common diseases and 3000 shared controls. Nature 2007;447(7145):661–678.CrossRefGoogle Scholar
Zeggini, E.Weedon, M.N.Lindgren, C.M.Frayling, T.M.Elliott, K.S.Lango, H.et al.Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 2007;316(5829):1336–1341 [epub 2007 Apr 26]CrossRefGoogle ScholarPubMed
van Os, JLinscott, RJMyin-Germeys, IDelespaul, PKrabbendam, L.A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychol Med, in press.Google Scholar
Johns, L.C.van Os, J.The continuity of psychotic experiences in the general population. Clin Psychol Rev 2001;21(8):1125–1141.CrossRefGoogle ScholarPubMed
McGrath, J.J.Myths and plain truths about schizophrenia epidemiology–the NAPE lecture 2004. Acta Psychiatr Scand 2005;111(1):4–11.CrossRefGoogle ScholarPubMed
McGrath, J.J.The surprisingly rich contours of schizophrenia epidemiology. Arch Gen Psychiatry 2007;64(1):14–16.CrossRefGoogle ScholarPubMed
Myin-Germeys, I.van Os, J.Schwartz, J.E.Stone, A.A.Delespaul, P.A.Emotional reactivity to daily life stress in psychosis. Arch Gen Psychiatry 2001;58(12):1137–1144.CrossRefGoogle ScholarPubMed
Allardyce, J.Gaebel, W.Zielasek, J.van Os, J.Deconstructing Psychosis Conference February 2006. The validity of schizophrenia and alternative approaches to the classification of psychosis. Schizophr Bull 2007;33:863–867.CrossRefGoogle Scholar
Hall, D.H.Rahman, T.Avery, P.J.Keavney, B.INSIG-2 promoter polymorphism and obesity related phenotypes: association study in 1428 members of 248 families. BMC Med Genet 7 2006 Nov 83.CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.