Vilain J, Galliot A-M, Durand-Roger J, Leboyer M, Llorca P-M, Schürhoff F, Szöke A
Inserm U 955, équipe de psychiatrie génétique, département de génomique médicale, institut Mondor de recherches biomédicales (IMRB), 94000 Créteil, France.
Encephale. 2013 Feb;39(1):19-28. doi: 10.1016/j.encep.2011.12.007. Epub 2012 Nov 21.
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.
在基因同质人群中已发现精神分裂症发病率存在差异的证据,这取决于特定环境特征在时间或空间上的变化。在病因学研究中考虑环境风险因素的影响,使环境在精神病性疾病研究中处于前沿位置。各种环境因素,如城市化、移民、大麻、童年创伤、感染源、产科并发症和社会心理因素,都与精神分裂症的发病风险相关。这些风险因素可以是生物学、物理、心理以及社会方面的,并且可能在个体生命中的不同时期(胎儿期、童年、青春期和成年早期)起作用。虽然其中一些因素在个体层面起作用,但其他因素在群体层面起作用,调节个体风险。这些因素可以直接影响精神分裂症的发展,或者另一方面作为尚未确定的直接相关因素的标志物。
本文总结了关于该主题的当前知识。通过搜索引擎PubMed进行了广泛的文献检索。在以下论文中选择并阐述了八个风险因素:城市化(或居住在城市地区)、大麻、移民(以及种族密度)、产科并发症、出生季节、感染源(以及炎症反应)、社会人口统计学因素和童年创伤。对于这些因素中的每一个,我们根据手头研究的数量、类型、质量和一致性,提供关于风险重要性、易感期、对因素背后可能机制的假设以及当前研究所提供的证据水平(充分、中等或不足)的信息。一些因素,如大麻,在对精神分裂症发展的影响方面是“独特的”,因为它仅代表一个风险因素。其他因素,如产科并发症,则是“组合的”,因为它们包括可以影响精神分裂症发展的各种子因素。
所审查的数据清楚地表明环境因素会影响精神分裂症的发病风险。对于某些因素——大麻、移民、城市化、产科并发症、季节——有足够的证据证明与精神分裂症风险存在关联。然而,这种关联仍然较弱(特别是对于季节因素)。除了大麻之外,尚未能建立直接联系。关于其余三个因素——童年创伤、感染源、社会人口统计学因素——现有证据不足。关于所有环境因素的一个主要限制是由于研究是在地理上有限的人群中进行的,因此结果难以推广。目前的知识状态不允许我们确定这些因素可能起作用的机制。
需要进一步研究以填补我们对该主题理解上的空白。为了满足这一需求,设立了一个欧洲合作项目(欧洲基因 - 环境相互作用研究[EU GEI])。该研究提议分析那些影响欧洲不同国家精神分裂症发病率的环境因素,包括农村和城市地区、移民和本地人群,以及它们与遗传因素的相互作用。