An expansive approach to examining the paternal origins of mental disorders.
An expansive approach to examining the paternal origins of mental disorders.
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DOI：
10.1038/s41390-021-01886-9
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发表时间：
2022-03
影响因子：
3.6
通讯作者：
Stroustrup, Annemarie
中科院分区：
文献类型：
--
作者：
Stroustrup, Annemarie
在这一期的《儿科研究》中，Vervoot、Delger和Soubry回顾了父亲受孕时的年龄对后代精神障碍发展的影响。他们关注父亲年龄可能起作用的六种情况：自闭症谱系障碍、精神分裂症、注意力缺陷/多动障碍、双相情感障碍、强迫症和抽动秽语综合征。他们还评论了缺乏流行病学证据来证明父亲年龄在其他精神疾病如自杀和药物滥用中的作用。在回顾以前的研究集中在感兴趣的条件的病因学，作者注意到之间的相互作用，促进遗传，表观遗传和环境因素在症状性疾病的发展。他们指出，不仅多种影响有助于表型的表现，而且不同的病因机制可能相互作用以增强或抑制疾病的发展。例如，导致父亲特定表型的遗传因素可能会使他倾向于在生命的早期或晚期养育孩子的行为。较早的养育子女的结果是由不太成熟的父母在一个社会经济不太安全的家庭抚养子女，从而产生一个可能增强后代特定表型的社会环境。因此，父亲的基因直接影响孩子所经历的环境。相比之下，晚育会增加有毒环境的暴露，这可能会影响配子上的表观遗传标记，增强或抑制父亲表型的传播。Vervoot等人因此将广角发育透镜应用于这六种情况的起源问题，“巴克假说”或健康和疾病的发展起源框架1，以建立健康和疾病的父亲起源范式，该范式至少从2018. [2]因此，他们对疾病预测问题采取了“基因组学”方法，提出了一个概念框架，用以解决父亲年龄在后代特定疾病发展中的作用。这种方法由Christopher Wild在2005年提出，强调在理解人类疾病进展时需要考虑环境影响。具体而言，干扰组被定义为“包括从产前开始的生命过程环境暴露（包括生活方式因素）”3，旨在补充全基因组关联研究，以寻找疾病的预测因子和促成因素。
In this issue of Pediatric Research, Vervoot, Delger, and Soubry review what is known about the impact of paternal age at conception and the development of mental disorders in offspring. They focus on six conditions for which paternal age may play a role: autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder, and Tourette syndrome. They also comment on the paucity of epidemiological evidence for a role of paternal age in other psychiatric conditions such as suicidality and substance abuse. In reviewing prior studies focused on the etiology of the conditions of interest, the authors note the interplay between contributing genetic, epigenetic, and environmental factors in the development of symptomatic disease. Not only do multiple influences contribute to the manifestation of phenotype, they note, but distinct etiological mechanisms likely interact to enhance or suppress disease development. For example, genetic factors contributing to a specific phenotype in the father might predispose him to behavior that results in fathering a child earlier or later in life. Earlier parenting results in childrearing by less mature parents in an often less socioeconomically secure household, resulting in a social environment that could potentially enhance specific phenotypes in the offspring. Thus, paternal genetics directly influences the environment that the child experiences. In contrast, later parenting allows for increased toxic environmental exposures that could impact epigenetic marks on gametes, enhancing or suppressing transmission of the father’s phenotype.Vervoot et al. thereby apply a wide-angle developmental lens to the question of the origins of these six conditions, adapting the “Barker Hypothesis” or Developmental Origins of Health and Disease framework 1 to build upon the Paternal Origins of Health and Disease paradigm that has been circulating in the literature since at least 2018. 2 As such, they take an “exposomics” approach to the question of disease prediction, proposing a conceptual framework with which to address the role of paternal age in the development of specific disorders in offspring. This approach, conceptualized by Christopher Wild in 2005, stresses the need to include environmental influences in the understanding of human disease progression. Specifically, the exposome is defined as “encompassing life-course environmental exposures (including lifestyle factors), from the prenatal period onwards” 3 and is intended to complement genome-wide association studies in the search for predictors of and contributors to disease.
影响因子：
3.8
作者：
Soubry A
通讯作者：
Soubry A