Department of Pathology,Dalhousie University,Halifax,NS,Canada.
Department of Pharmacology,Dalhousie University,Halifax,NS,Canada.
Psychol Med. 2018 Sep;48(12):1925-1936. doi: 10.1017/S003329171700383X. Epub 2018 Jan 15.
Schizophrenia and other types of psychosis incur suffering, high health care costs and loss of human potential, due to the combination of early onset and poor response to treatment. Our ability to prevent or cure psychosis depends on knowledge of causal mechanisms. Molecular genetic studies show that thousands of common and rare variants contribute to the genetic risk for psychosis. Epidemiological studies have identified many environmental factors associated with increased risk of psychosis. However, no single genetic or environmental factor is sufficient to cause psychosis on its own. The risk of developing psychosis increases with the accumulation of many genetic risk variants and exposures to multiple adverse environmental factors. Additionally, the impact of environmental exposures likely depends on genetic factors, through gene-environment interactions. Only a few specific gene-environment combinations that lead to increased risk of psychosis have been identified to date. An example of replicable gene-environment interaction is a common polymorphism in the AKT1 gene that makes its carriers sensitive to developing psychosis with regular cannabis use. A synthesis of results from twin studies, molecular genetics, and epidemiological research outlines the many genetic and environmental factors contributing to psychosis. The interplay between these factors needs to be considered to draw a complete picture of etiology. To reach a more complete explanation of psychosis that can inform preventive strategies, future research should focus on longitudinal assessments of multiple environmental exposures within large, genotyped cohorts beginning early in life.
精神分裂症和其他类型的精神病会导致患者遭受痛苦，增加医疗保健费用，并丧失人类潜能，这是由于发病早和治疗反应不佳的双重原因。我们能否预防或治疗精神病取决于对病因机制的了解。分子遗传学研究表明，数千种常见和罕见的变异都会增加患精神病的遗传风险。流行病学研究已经确定了许多与增加精神病风险相关的环境因素。然而，没有任何单一的遗传或环境因素足以单独导致精神病。随着许多遗传风险变异的积累和多种不良环境因素的暴露，患精神病的风险会增加。此外，环境暴露的影响可能取决于遗传因素，这是通过基因-环境相互作用实现的。迄今为止，只确定了少数几种具体的基因-环境组合会导致精神病风险增加。可复制的基因-环境相互作用的一个例子是 AKT1 基因中的常见多态性，它使携带者在经常使用大麻时容易患上精神病。通过对双胞胎研究、分子遗传学和流行病学研究结果进行综合分析，概述了导致精神病的许多遗传和环境因素。需要考虑这些因素之间的相互作用，以全面了解病因。为了更全面地解释精神病，从而为预防策略提供信息，未来的研究应该集中在对大样本人群进行早期、多环境暴露的纵向评估，这些人群经过基因分型。
