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

Published online by Cambridge University Press:  28 April 2020

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

Cet article étudie les principaux mécanismes de régulation de la transmission dopaminergique et s'efforce d’identifier les gènes dont la mutation serait susceptible d'altérer cette transmission.

Summary

Summary

In a first paper we have shown the advantage of the «genes candidate» method for identifying DNA sequences predisposing to schizophrenia. This strategy assumes precise knowledge of pathophysiological mechanism underlying the disease. We have discussed the presence of a dopaminergic transmission disturbance (hyper and/or hypodopaminergy) in schizophrenia. In this paper, we shall study in details the parameters regulating this transmission i.e. the number of available synapses in the brain, the functional state of dopaminergic synapses and the structure of circuitry in which dopaminergic neurons are inserted. For every parameter, we shall make a distinction between genetic and epigenetic regulating factors and we shall try to describe molecular mechanisms at work. The best candidates for a mutation are genes coding for proteins intervening in DA metabolism or synaptic physiology: tyrosine hydroxylase, MAO, D2 or D1 receptors, G proteins, DA reuptake molecular complex and cotransmitters as CCK. Heteroreceptors on pre- or post-synaptic side are especially important in modulation of DA transmission and are also candidate. Other genes are partially controlling ontogeny of dopaminergic systems and neuronal plasticity. These genes are still largely unknown but their study is in progress. It has been reported that schizophrenic brains display alterations in cell organisation. Mutation of these genes could be responsible for these changes.

Keywords

génes candidatstyrosine hydroxylaserécepteurs D2MAOhétérorécepteurs«genes candidate» methodtyrosine hydroxylaseD2 receptorsMAOheteroreceptors
Type
Article original
Information
Psychiatry and Psychobiology , Volume 3 , Issue 5 , 1988 , pp. 305 - 319
Copyright
Copyright © European Psychiatric Association 1988

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