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Schizophrénie: l’hypothèse dopaminergique à l’épreuve de la génétique moléculaire. I.

Published online by Cambridge University Press:  28 April 2020

D. Campion
D. Campion*
Affiliation:
CHSR, 4, rue Paul-Eluard, 76300Sotteville-les-Rouen, France
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Résumé

L’essor de la génétique moléculaire renouvelle l’intérêt pour les études de linkage dans les maladies mentales et devrait nous permettre d’identifier dans le futur les séquences de DNA prédisposant à des phénotypes anormaux. Dans cet article, nous allons d’abord rappeler les principales données obtenues par la génétique classique concernant la schizophrénie, puis nous décrirons une des stratégies de recherche actuellement utilisée: la méthode des gènes candidats. L’emploi de cette méthode nécessite des hypothèses physiopathologiques précises sur l’étiologie de la maladie. Nous serons donc amenès à discuter l’hypothèse d’un dérèglement de la transmission dopaminergique.

Dans un second article à paraître dans un prochain numéro de «Psychiatrie & Psychobiologie» nous étudierons plus en détail les facteurs régulant cette transmission dopaminergique et nous tenterons de définir en fonction des connaissances actuelles les gènes potentiellement mutés.

Summary

Summary

The development of molecular genetics has brought a new interest in linkage analysis in mental diseases and should enable the identification of DNA sequences with a predisposition to abnormal phenotypes. In this paper we first recall basic data from classical genetic studies on schizophrenia.

If there appears to be a familial aggregation of the disease, lack of mendelian proportion in transmission, contradictory results in segregation analysis, methodological difficulties in adoption studies, do not allow one to conclude that it is explicitly of genetic origin. Howewer, data are compatible with such a hypothesis.

Today, the interest in linkage studies is renewed by the use of RFLP (restriction fragment length polyporphisms). We describe a strategy based on the “candidate genes” method. This approach has an advantage in its use of random fragments but does not resolve questions regarding heterogeneity and incomplete penetrance. morever, this strategy assumes that there is a precise hypothesis concerning disease etiology. The existence of a dopaminergic transmission disturbance is discussed, with particular emphasis on a bipolar theory, which includes positive and negative symptoms.

In a further paper, we shall study in detail the factors regulating this dopaminergic transmission, in order to define potential mutated genes.

Keywords

schizophréniegénes candidatshypothèse bipolaireschizophreniacandidate genesbipolar hypothesis
Type
Article original
Information
Psychiatry and Psychobiology , Volume 3 , Issue 2 , 1988 , pp. 73 - 80
Copyright
Copyright © European Psychiatric Association 1988

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References

Références

Abrams, R. & Taylor, M.A. (1983) The genetics of schizophrenia: a reassessment using modern criteria. Am. J. Psychiat. 140, 171–175Google ScholarPubMed
Alpert, M.Friedhof, A.J.Marcos, A.J. & Diamont, F. (1978) Paradoxal reaction to L-DOPA in schizophrenic patients. Am. J. Psychiatry. 35, 1329–1332Google Scholar
Andreasen, N.C.Olsen, S.A.Dennert, J.W. & Smith, M.R. (1982) Ventricular enlargement in schizophrenia: relationship to positive and negative symptoms. Am. J. Psychiatry. 139, 297–302Google ScholarPubMed
Baron, M.Gruen, R.Kane, J. & Asnis, L. (1985) Modern research criteria and the genetics of schizophrenia. Am. J. Psychiatry. 142, 697–701Google ScholarPubMed
Bowers, M.B. (1974) Central DA turnover in schizophrenia syndromes. Arch. Gen. Psychiatry. 31, 50–54CrossRefGoogle Scholar
Boyer, P., & Dreyfus, J.F. (1985) Evaluation of the disinhibitory effect of low dosage of some neuroleptics and the negative symptoms in schizophrenia. Schizophr. Bull.(suppl.)Google Scholar
Boyer, P. & Puech, A.J. (1987) Modalités d'action clinique des neuroleptiques: substances, doses, instruments de mesure utilisés. Psychiatrie Psychobiologie. II, 296–305Google Scholar
Carlier, M. (1980) La méthode des adoptions dans l'analyse génétique des psychoses schizophrèniques - revue critique. Psychiatrie Enfant. 23, 507–585Google Scholar
Carter, C.I. & Chung, C.S. (1980) Segregation analysis of schizophrenia under a mixed genetic model. Hum. Hered. 30, 350–356CrossRefGoogle Scholar
Cassou, B.Schiff, M. & Stewart, J. (1980) Génétique et schizophrénie: réévaluation d'un consensus. Psychiatrie Enfant. 23, 87–201Google Scholar
Cavalli-Sforza, L.L. & King, M.C. (1986) Detecting linkage for genetically heterogenous diseases and detecting heterogeneity with linkage data. Am. J. Hum. Genet. 38, 599–616Google Scholar
Chouinard, G. & Jones, B. (1978) Schizophrenia as dopamine deficiency disease. Lancet. ii, 99–100CrossRefGoogle Scholar
Chouinard, G. & Jones, B. (1980) Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics. Am. J. Psychiatry. 137, 16–21Google ScholarPubMed
Costentin, J. (1981) Revue des principaux arguments étayant l'hypothèse d'une hyperactivitédopaminergique dans la schizophrénie. In: Actualit's de la Schizophrénie(Pichot P., ed.), Puf, 169-193Google Scholar
Crawley, J.C. (1986) Dopamine D2 receptors in schizophrenia studied in vivo. Lancet. ii, 224–225CrossRefGoogle Scholar
Cross, A.J. et al. (1984) Dopamine receptor changes in schizophrenia in relation to the disease process and movement disorders. J. Neural Transm.(suppl.), 18, 265–272Google Scholar
Crow, T.J. (1985) The two-syndrome concept: origins and current status. Schizophr. Bull. 11, 471–486CrossRefGoogle ScholarPubMed
Debray, Q. (1978) Rapport de Psychiatrie, Congrès de Charleroi, 77-253Google Scholar
De Lisi, L.Goldin, L.Hamovit, J.Maxwell, E.Kurtz, D. & Gershon, E. (1986) A family study of the association of increased ventricular size with schizophrenia. Arch. Gen. Psychiatry. 43, 148–153CrossRefGoogle Scholar
Egeland, J. et al.(1987) Bipolar affective disorders linked to DNA markers on chromosome 11. Nature. 325, 783–787CrossRefGoogle ScholarPubMed
Gattaz, W. et al.(1983) Dopamine and noradrenalin in the cerebrospinal fluid of schizophrenic patients. Psychiatry Res. 8, 243–250CrossRefGoogle ScholarPubMed
Goldin, L.R.De Lisi, L.E. & Gershon, E.S. (1987) Unravelling the relationship between genetic and environmental risk factors in psychiatric disorders. Br. J. Psychiatry. 151, 302–305CrossRefGoogle ScholarPubMed
McGuffin, P., Farmer, A. & Gottesman, I.I. (1987) Is there really a split in schizophrenia? The genetic evidence. Br. J. Psychiatry. 150, 581–592CrossRefGoogle ScholarPubMed
McGuffin, P.Festenstein, H. & Murray, R. (1983) A family study of HLA antigens and other genetic markers in schizophrenia. Psychol. Medicine. 13, 31–43CrossRefGoogle Scholar
Gusella, J. et al.(1983) A polymorphic DNA marker genetically linked to Huntington's disease. Nature. 306, 234–238CrossRefGoogle ScholarPubMed
Heston, L.L. & Denney, D. (1968) Interactions between early life experience and biological factors in schizophrenia. In: Transmission of Schizophrenia. (Rosenthal, D. & Kety, S., eds.), Pergamon, OxfordGoogle Scholar
Lecrubier, Y. (1987) Doit-on envisager une classification des neuroleptiques tenant mieux compte des mécanismes d'action et des différents syndromes cibles ?. Psychiatrie Psychobiologie. 2, 232–237Google Scholar
Lecrubier, Y.Puech, A.J.Simon, P. & Widlocher, D. (1980) Schizophrénie: hyper- ou hypofonctionnement du système dopaminergique? Une hypothèse bipolaire. Psychol. Méd. 12, 11, 2431–2439Google Scholar
Lee, T. & Seeman, P. (1978) Binding of neuroleptics and apomorphine in schizophrenic brains. Nature. 274, 897–900CrossRefGoogle ScholarPubMed
Lee, T. & Seeman, P. (1980) Elevation of brain neuroleptic/dopamine receptors in schizophrenia. Am. J. Psychiatry. 137, 191–197Google Scholar
Mackay, A.V.P. et al.(1982) Increased brain dopamine and dopamine receptors in schizophrenia. Arch. Gen. Psychiatry. 39, 991–997CrossRefGoogle Scholar
Mackay, A.V.P. (1980) Positive and negative schizophrenic symptoms and the role of dopamine. Br. J. Psychiatry. 137, 379–386CrossRefGoogle ScholarPubMed
Meller, E.Bohmaker, K.Rosengarten, H. & Friedhoff, A.J. (1982) Chronic haloperidol does not increase specific dopamine receptor binding in rat frontal cortex. Res. Commun. Chem. Pathol. Pharmacol. 37, 323–332Google Scholar
Meltzer, H.Y. (1976) Serum prolactin levels in unmedicated schizophrenic patients. Arch. Gen. Psychiatry. 31, 564–568CrossRefGoogle Scholar
Nasrallah, H.A.Jacob, C.G.Mc Calley-Whitters, M. & Kuperman, S. (1982) Cerebral ventricular enlargement in subtypes of chronic schizophrenia. Arch. Gen. Psychiatry. 39, 774–777CrossRefGoogle ScholarPubMed
O'Rourke, D.H.Gottesman, I.Suarez, B.K.Rice, J. & Reich, T. (1982) Refutation of the general single locus model for the etiology of schizophrenia Am. J. Hum. Genet. 34, 630–649Google ScholarPubMed
Ott, J. (1984) The number of families required to detect or exclude linkage heterogeneity. Am. J. Hum. Genet. 39, 159–165Google Scholar
Owen, F. et al.(1978) Increased dopamine receptor sensitivity in schizophrenia. Lancet. ii, 223–225CrossRefGoogle Scholar
Petit, P.Zann, M. & Colonna, L. (1984) Etude contrôlée de l'effet désinhibiteur de faibles doses de sulpiride dans les psychoses schizophréniques déficitaires. Encéphale. 10, 25–28Google Scholar
Pope, H.G.Jonas, J.M.Cohen, B.M. & Lipinski, J.F. (1982) Failure tofind evidence of schizophrenia in first-degree relatives of schizophrenic probands. Am. J. Psychiatry. 139, 826–827Google Scholar
Post, R.Fink, E.Carpenter, W.T. & Goodwin, F.K. (1975) CSF amine metabolites in acute schizophrenia. Arch. Gen. Psychiatry. 32, 1063–1069CrossRefGoogle Scholar
Puech, A.J.Brochet, O.Lecrubier, Y. & Simon, P. (1980) Neuroleptiques: activateurs ou inhibiteurs du système dopaminergique. Psychol. Méd.12, 11, 2427–2430Google Scholar
Rao, D.C.Morton, N.E., Gottesman, I. & Lew, R. (1981) Path analysis of qualitative data on pairs of relatives. Application to schizophrenia. Hum. Hered. 31, 325–333CrossRefGoogle Scholar
Reveley, A.M.Reveley, M.A. & Chitkara, B. (1984a) The genetie basis of cerebral ventricular volume. Psychiatry Res. 13, 261–266CrossRefGoogle Scholar
Reveley, A.M.Reveley, M.A. & Murray, R.M. (1984b) Cerebral ventricular enlargement in non-genetic schizophrenia: a controlled twin study. Br. J. Psychiatry. 144, 89–93CrossRefGoogle Scholar
Richelson, E. (1985) Pharmacology of neuroleptic in use in the United States J. Clin. Psychiatry. 46, 8–14Google ScholarPubMed
Risch, N. & Baron, M. (1984) Segregation analysis of schizophrenia and related disorders. Am. J. Hum. Genet. 36, 1039–1059Google ScholarPubMed
Scatton, B. (1986) Effets biochimiques des neuroleptiques. Séminaire de Psychiatrie Biologique, T 7 Fournier, 127–158Google Scholar
Schulsinger, F. et al.(1984) Cerebral ventricular size in the offspring of schizophrenic mothers. A preliminary study. Arch. Gen. Psychiatry. 41, 602–606CrossRefGoogle ScholarPubMed
Seeman, P. (1980) Brain dopamine receptors. Pharmacol. Rev. 32, 229–313Google ScholarPubMed
Sturt, E. & Mc Guffin, P. (1985) Can linkage and marker association resolve the genetic aetiology of psychiatric disorders?. Review and argument. Psychol. Med. 455–462CrossRefGoogle ScholarPubMed
Tecott, L.H.Kwong, L.Uhr, S. & Peroutka, S. (1986) Differential modulation of dopamine D2 receptors by chronic haloperidol, nitrendipine and pimozide. Biol. Psychiatry. 21, 1114–1122CrossRefGoogle ScholarPubMed
Tsuang, M.T.Winokur, G. & Crowe, R.R. (1980) Morbidity risks of schizophrenia and affective disorders among first-degree relatives of patients with schizophrenia, mania, depression and surgical conditions. Brit. J. Psychiatry. 137, 497–504CrossRefGoogle ScholarPubMed
Turner, W.J. (1979) Genetic markers for schizotaxia. Biol. Psychiatry. 14, 177–205Google ScholarPubMed
Weinberger, D.R. (1984) Computed tomography findings in schizophrenia: speculation on the meaning of it all. J. Psychiatry Res. 477–490CrossRefGoogle Scholar
Wender, P.Rosenthal, D.Kety, S.Schulsinger, F. & Welner, J. (1974) Crossfostering, a research strategy for clarifying the role of genetic experiential factors in the etiology of schizophrenia. Arch. Gen. Psychiatry. 30, 121–128CrossRefGoogle ScholarPubMed
Wong, D.F. et al.(1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science. 234, 1558–1562CrossRefGoogle ScholarPubMed
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