Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
New York State Psychiatric Institute, New York, NY, USA.
J Child Psychol Psychiatry. 2019 Feb;60(2):119-132. doi: 10.1111/jcpp.12877. Epub 2018 Feb 23.
For decades, economists and sociologists have documented intergenerational transmission of socioeconomic disadvantage, demonstrating that economic, political, and social factors contribute to 'inherited hardship'. Drawing on biological factors, the developmental origins of adult health and disease model posits that fetal exposure to maternal prenatal distress associated with socioeconomic disadvantage compromises offspring's neurodevelopment, affecting short- and long-term physical and mental health, and thereby psychosocial standing and resources. Increasing evidence suggests that mother-to-child influence occurs prenatally, in part via maternal and offspring atypical HPA axis regulation, with negative effects on the maturation of prefrontal and subcortical neural circuits in the offspring. However, even this in utero timeframe may be insufficient to understand biological aspects of the transmission of factors contributing to disadvantage across generations.
We review animal studies and emerging human research indicating that parents' childhood experiences may transfer epigenetic marks that could impact the development of their offspring independently of and in interaction with their offspring's perinatal and early childhood direct exposures to stress stemming from socioeconomic disadvantage and adversity.
Animal models point to epigenetic mechanisms by which traits that could contribute to disadvantage may be transmitted across generations. However, epigenetic pathways of parental childhood experiences influencing child outcomes in the next generation are only beginning to be studied in humans. With a focus on translational research, we point to design features and methodological considerations for human cohort studies to be able to test the intergenerational transmission hypothesis, and we illustrate this with existing longitudinal studies.
Epigenetic intergenerational transmission, if at play in human populations, could have policy implications in terms of reducing the continuation of disadvantage across generations. Further research is needed to address this gap in the understanding of the perpetuation of compromised lives across generations.
几十年来,经济学家和社会学家记录了代际社会经济劣势的传递,表明经济、政治和社会因素促成了“继承的苦难”。发展起源于成年健康和疾病模型利用生物学因素,假设胎儿在母孕期暴露于与社会经济劣势相关的母体产前压力会损害后代的神经发育,影响短期和长期的身心健康,从而影响社会心理地位和资源。越来越多的证据表明,母婴影响发生在产前,部分是通过母婴和后代非典型的 HPA 轴调节,对后代前额叶和皮质下神经回路的成熟产生负面影响。然而,即使是这个宫内时间框架也可能不足以理解导致代际劣势的因素的生物学方面。
我们回顾了动物研究和新兴的人类研究,这些研究表明,父母的童年经历可能会传递表观遗传标记,这些标记可能会影响后代的发育,而不受其后代因社会经济劣势和逆境而产生的围产期和幼儿期直接压力的影响,也不受其影响。
动物模型指出了表观遗传机制,通过这些机制,可能导致劣势的特征可以在代际之间传递。然而,父母童年经历影响下一代儿童结果的表观遗传途径在人类中才刚刚开始研究。我们以转化研究为重点,指出了人类队列研究的设计特点和方法考虑因素,以便能够测试代际传递假设,并通过现有的纵向研究来说明这一点。
如果在人类群体中存在表观遗传代际传递,这可能会对减少代际劣势的延续产生政策影响。需要进一步研究来解决对代际传递的理解的这一差距,以了解几代人生活的恶化是如何持续的。