Gene-environment interactions in severe mental illness.
Gene-environment interactions in severe mental illness.
复制标题
DOI：
10.3389/fpsyt.2014.00048
复制
发表时间：
2014
影响因子：
4.7
通讯作者：
Uher R
中科院分区：
文献类型：
--
作者：
Uher R
严重精神疾病（SMI）是一个广泛的类别，包括精神分裂症、双相情感障碍和严重抑郁症。遗传倾向和环境暴露在重度精神分裂症的发展中都起重要作用。多种证据表明，遗传因素和环境因素的作用是相互依赖的。基因-环境相互作用可能是高遗传性疾病的强环境因素、重度精神障碍双胞胎研究中共同环境影响的低估计以及双胞胎和分子遗传率估计之间的遗传率差距等悖论的基础。重度精神障碍父母的子女更容易受到产前和产后环境暴露的影响，表明遗传倾向的表达与环境有关。在过去的十年中，已经确定了候选基因中涉及特定分子变异的基因-环境相互作用。重复的发现包括AKT1基因多态性与大麻使用在精神病发展中的相互作用，以及血清素转运体基因长度多态性与儿童虐待在持续性抑郁症发展中的相互作用。双相情感障碍的研究还不够充分，只有一项研究表明BDNF基因的功能多态性与引发双相情感障碍的压力生活事件之间存在相互作用。首次对基因-环境相互作用的系统研究发现，CTNNA3的多态性可能使发育中的大脑对子宫内巨细胞病毒的致病作用敏感，从而导致成年后的精神分裂症。全基因组调查的策略可能包括流行病学和遗传学研究工作之间的协调，大样本中多种环境因素的系统评估，以及遗传变异的优先排序。
Severe mental illness (SMI) is a broad category that includes schizophrenia, bipolar disorder, and severe depression. Both genetic disposition and environmental exposures play important roles in the development of SMI. Multiple lines of evidence suggest that the roles of genetic and environmental factors depend on each other. Gene–environment interactions may underlie the paradox of strong environmental factors for highly heritable disorders, the low estimates of shared environmental influences in twin studies of SMI, and the heritability gap between twin and molecular heritability estimates. Sons and daughters of parents with SMI are more vulnerable to the effects of prenatal and postnatal environmental exposures, suggesting that the expression of genetic liability depends on environment. In the last decade, gene–environment interactions involving specific molecular variants in candidate genes have been identified. Replicated findings include an interaction between a polymorphism in the AKT1 gene and cannabis use in the development of psychosis and an interaction between the length polymorphism of the serotonin transporter gene and childhood maltreatment in the development of persistent depressive disorder. Bipolar disorder has been underinvestigated, with only a single study showing an interaction between a functional polymorphism in the BDNF gene and stressful life events triggering bipolar depressive episodes. The first systematic search for gene–environment interactions has found that a polymorphism in CTNNA3 may sensitize the developing brain to the pathogenic effect of cytomegalovirus in utero, leading to schizophrenia in adulthood. Strategies for genome-wide investigations will likely include coordination between epidemiological and genetic research efforts, systematic assessment of multiple environmental factors in large samples, and prioritization of genetic variants.
登录
查看更多内容
影响因子：
10.5
作者：
Collip, Dina;Myin-Germeys, Inez;van Winkel, Ruud
通讯作者：
van Winkel, Ruud
影响因子：
120.7
作者：
Binder, Elisabeth B.;Bradley, Rebekah G.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
17.7
作者：
Brown, AS;van Os, J;Susser, ES
通讯作者：
Susser, ES
影响因子：
6.9
作者：
Collins, A. L.;Kim, Y.;Sklar, P.;O'Donovan, M. C.;Sullivan, P. F.
通讯作者：
Sullivan, P. F.
影响因子：
6.7
作者：
Brown AS
通讯作者：
Brown AS