Influence de l’âge de début des troubles de la maladie d’Alzheimer sur la mémoire de travail verbale et le métabolisme cérébral : Corrélations cognitivo-métaboliques

Abstract

L’impact de facteurs de risque environnementaux met aujourd’hui l’environnement au cœur des modèles étiopathogéniques de la schizophrénie. Divers facteurs d’environnement tels que l’urbanicité, la migration, le cannabis, les traumatismes infantiles, les complications obstétricales et les facteurs psychosociaux, ont été associés au risque de survenue de troubles schizophréniques. Certains agissent au niveau de l’individu, d’autres agissent au niveau d’un groupe de population et viennent moduler le risque individuel. Par ailleurs, ces facteurs peuvent être directement liés à l’augmentation de la survenue des troubles ou être des marqueurs associés à d’autres facteurs plus directement impliqués, mais non encore identifiés. Cette revue de la littérature présente pour chacun des facteurs de risque, l’importance du risque, la période vulnérable et les hypothèses concernant le mécanisme d’action en indiquant le niveau de preuve dont nous disposons. Les facteurs étudiés sont tous associés à un risque augmenté de survenue de troubles schizophréniques. Le risque relatif associé à ces facteurs est modéré, mais l’exposition à ces facteurs concerne une large proportion de la population générale, leur risque attribuable est donc important (jusqu’à 35 % pour l’urbanicité). En ce qui concerne le mécanisme d’action, l’état actuel des connaissances ne permet pas de déterminer s’il existe une voie d’action commune ou si chaque facteur a une voie propre. Il est nécessaire de poursuivre les études concernant ces différents facteurs dans des contextes variés en les intégrant dans un modèle d’interaction entre facteurs d’environnement et entre gènes et environnement.Evidence of variations in schizophrenia incidence rates has been found in genetically homogenous populations, depending on changes within time or space of certain environmental characteristics. The consideration of the impact of environmental risk factors in etiopathogenic studies has put the environment in the forefront of research regarding psychotic illnesses. Various environmental factors such as urbanicity, migration, cannabis, childhood traumas, infectious agents, obstetrical complications and psychosocial factors have been associated with the risk of developing schizophrenia. These risk factors can be biological, physical, psychological as well as social and may operate at different times in an individual's life (fetal period, childhood, adolescence and early adulthood). Whilst some of these factors act on an individual level, others act on a populational level, modulating the individual risk. These factors can have a direct action on the development of schizophrenia, or on the other hand act as markers for directly implicated factors that have not yet been identified.This article summarizes the current knowledge on this subject. An extensive literature search was conducted via the search engine Pubmed. Eight risk factors were selected and developed in the following paper: urbanicity (or living in an urban area), cannabis, migration (and ethnic density), obstetrical complications, seasonality of birth, infectious agents (and inflammatory responses), socio-demographic factors and childhood traumas. For each of these factors, we provide information on the importance of the risk, the vulnerability period, hypotheses made on the possible mechanisms behind the factors and the level of proof the current research offers (good, medium, or insufficient) according to the amount, type, quality and concordance of the studies at hand. Some factors, such as cannabis, are “unique” in their influence on the development of schizophrenia since it labels only one risk factor. Others, such as obstetrical complications, are grouped (or “composed”) in that they include various sub-factors that can influence the development of schizophrenia.The data reviewed clearly demonstrates that environmental factors have an influence on the risk of developing schizophrenia. For certain factors – cannabis, migration, urbanicity, obstetrical complications, seasonality – there is enough evidence to establish an association with the risk of schizophrenia. This association, however, remains weak (especially for seasonality). With the exception of cannabis, no direct link can yet be established. Concerning the three remaining factors – childhood traumas, infectious agents, socio-demographic factors – the available proof is insufficient. One main limitation concerning all environmental factors is the generalization of results due to the fact that the studies were conducted on geographically limited populations. The current state of knowledge does not allow us to determine the mechanisms by which these factors may act.Further research is needed to fill the gaps in our understanding of the subject. In response to this need, a collaborative European project (European Study of Gene-Environment Interactions [EU GEI]) was set-up. This study proposes the analysis of those environmental factors that influence the incidence of schizophrenia in various European countries, in both rural and urban settings, migrant and native populations, as well as their interaction with genetic factors.