A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis.
A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis.
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DOI：
10.1016/j.neubiorev.2016.03.017
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发表时间：
2016-06
影响因子：
8.2
通讯作者：
Berk M
中科院分区：
文献类型：
--
作者：
Davis J;Eyre H;Jacka FN;Dodd S;Dean O;McEwen S;Debnath M;McGrath J;Maes M;Amminger P;McGorry PD;Pantelis C;Berk M
精神分裂症的风险通常被概念化，使用一个模型，这个模型需要两个因素来产生临床表型——第一个是基因易感性个体的早期启动，第二个是可能的环境侮辱。本文的目的是回顾文献并重新制定二元风险-脆弱性模型。我们从PUBMED电子数据库中获取了这篇叙述性综述的数据。我们的搜索条件不受语言或出版日期的限制。精神分裂症的发生可能是遗传易感性与产前维生素D暴露降低、病毒感染、吸烟智商、社会认知、大麻使用、社会失败、营养和童年创伤等多种易感性因素相互作用所致。这些遗传风险、环境风险和易损性因素很可能是累积的，相互作用的，并与神经发育易损性的关键时期有关。精神分裂症的发展可能比30年前最初提出的二元模型更复杂、更微妙。风险似乎受到一个更复杂的过程的影响，该过程涉及遗传风险与发生在神经发育活动关键时期的多种潜在相互作用的打击和易感性因素的交互作用，最终导致疾病状态的表达。这些风险在许多神经精神疾病和医学疾病中都很常见，这可能为非传染性疾病的共同预防和干预战略提供信息。
Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype—the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders.