Early life adversity and trajectories of cardiometabolic health, cognitive function and physical function: improving understanding of the mechanisms a

生命早期的逆境和心脏代谢健康、认知功能和身体功能的轨迹：增进对机制的理解

• 批准号: ES/M010317/1
• 负责人: Laura D Howe
• 金额: $ 21.01万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=ES%2FM010317%2F1
• 关键词: Early; life; adversity; trajectories; cardiometabolic

Good health starts in early life. In early childhood, children in 'healthy' families learn that they can rely on their carers for their physical and emotional wellbeing. This allows the child to develop behaviours and other assets that will enable them to maintain their own wellbeing in later life. When the family safety net is compromised in one or more ways, the emotional and physical development of young children is vulnerable. Early life adversity is a risk factor for adverse cardiometabolic health, and poorer cognitive and physical function - three aspects of healthy aging essential for longevity and the maintenance of independence in old age. Questions remain, however, about the pathways and mechanisms through which the adverse health consequences of early life adversity arise. Most research on this topic comes from studies with health measured at a single age in adulthood. Such studies cannot explore the dynamic relationships between early life adversity and changes in health across the life course. We will investigate this in longitudinal studies with repeated measures of health in 3 cohorts. Using repeated measures of health will enable us to assess whether some people remain resilient to the health effects of early adversity, whether some people with favourable health profiles at earlier ages experience deterioration in mid-life health, and the potential for reversibility, i.e. an improvement in health during mid-life. The role of adversity (e.g. abusive or dysfunctional relationships) and resources (e.g. social support) experienced in adulthood also remains uncertain. In all 3 cohorts, we will examine whether adversity and resources in adulthood explain or alter the relationship between early adversity and trajectories of health. Risk factors such as smoking and obesity play a role in the generation of health inequalities, and interventions that reduce these risk factors would reduce the adverse health consequences of early life adversity. However, most of this evidence comes from studies with single measurements of smoking, obesity, etc. In all 3 cohorts, we will use repeated measurements of smoking, alcohol use, physical activity, mental health and personality traits, and explore their role in the relationship between early life adversity and later health. Our approach will enable us to identify detrimental or health-promoting behavioural or psychological trajectories. Finally, insufficient attention has been given in the literature to the the biological mechanisms through which early life adversity affects later health. We will estimate the role of two biological processes, DNA methylation and cortisol, in the associations between early life adversity and trajectories of health.

良好的健康始于幼年。在幼儿时期，“健康”家庭中的儿童了解到，他们可以依靠照顾者来实现身心健康。这使孩子能够发展行为和其他资产，使他们能够在以后的生活中保持自己的幸福。当家庭安全网以一种或多种方式受到损害时，幼儿的情感和身体发育就会受到伤害。早年生活的逆境是心脏代谢健康不良、认知和身体功能较差的危险因素，这是健康老龄化的三个方面，对长寿和老年时保持独立性至关重要。然而，关于早期生活逆境产生不良健康后果的途径和机制仍然存在疑问。关于这一主题的大多数研究都来自于对成年期单一年龄的健康状况进行测量的研究。这些研究无法探索早期生活逆境与整个生命过程中健康变化之间的动态关系。我们将在纵向研究中调查这一点，在三个队列中重复测量健康状况。使用重复的健康测量将使我们能够评估一些人是否能够对早期逆境的健康影响保持弹性，是否一些在较早年龄拥有良好健康状况的人在中年健康状况会恶化，以及可逆性的可能性，即中年健康状况的改善。成年期经历的逆境（如虐待或功能失调的关系）和资源（如社会支持）的作用也仍然不确定。在所有三个队列中，我们将检查成年期的逆境和资源是否解释或改变早期逆境与健康轨迹之间的关系。吸烟和肥胖等风险因素在产生健康不平等方面发挥作用，减少这些风险因素的干预措施将减少早年生活逆境对健康的不利影响。然而，这些证据大多来自吸烟、肥胖等单一测量的研究。在所有三个队列中，我们将使用吸烟、饮酒、体育活动、心理健康和人格特征的重复测量，并探索它们在早期生活逆境与后期健康之间的关系中的作用。我们的方法将使我们能够确定有害或促进健康的行为或心理轨迹。最后，文献中对早期生活逆境影响后期健康的生物学机制的关注不足。我们将估计两个生物过程的作用，DNA甲基化和皮质醇，在早期生活逆境和健康轨迹之间的关联。

项目成果

Childhood adversity and DNA methylation in two population-based cohorts.

• DOI: 10.1038/s41398-018-0307-3
• 发表时间: 2018-12-03
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Houtepen LC;Hardy R;Maddock J;Kuh D;Anderson EL;Relton CL;Suderman MJ;Howe LD
• 通讯作者: Howe LD

Is disrupted sleep a risk factor for Alzheimer's disease? Evidence from a two-sample Mendelian randomization analysis.

• DOI: 10.1093/ije/dyaa183
• 发表时间: 2021-07-09
• 期刊: International journal of epidemiology
• 影响因子: 7.7
• 作者: Anderson EL;Richmond RC;Jones SE;Hemani G;Wade KH;Dashti HS;Lane JM;Wang H;Saxena R;Brumpton B;Korologou-Linden R;Nielsen JB;Åsvold BO;Abecasis G;Coulthard E;Kyle SD;Beaumont RN;Tyrrell J;Frayling TM;Munafò MR;Wood AR;Ben-Shlomo Y;Howe LD;Lawlor DA;Weedon MN;Davey Smith G
• 通讯作者: Davey Smith G

Adverse childhood experiences in the children of the Avon Longitudinal Study of Parents and Children (ALSPAC).

• DOI: 10.12688/wellcomeopenres.14716.1
• 发表时间: 2018-01-01
• 期刊: Wellcome open research
• 作者: Houtepen, Lotte C;Heron, Jon;Howe, Laura D
• 通讯作者: Howe, Laura D

Modeling Exposure to Multiple Childhood Social Risk Factors and Physical Capability and Common Affective Symptoms in Later Life.

• DOI: 10.1177/0898264316680434
• 发表时间: 2018-03
• 期刊: Journal of aging and health
• 影响因子: 2.8
• 作者: Caleyachetty R;Hardy R;Cooper R;Richards M;Howe LD;Anderson E;Kuh D;Stafford M
• 通讯作者: Stafford M

Education, intelligence and Alzheimer's disease: evidence from a multivariable two-sample Mendelian randomization study.

• DOI: 10.1093/ije/dyz280
• 发表时间: 2020-08-01
• 期刊: International journal of epidemiology
• 影响因子: 7.7
• 作者: Anderson EL;Howe LD;Wade KH;Ben-Shlomo Y;Hill WD;Deary IJ;Sanderson EC;Zheng J;Korologou-Linden R;Stergiakouli E;Davey Smith G;Davies NM;Hemani G
• 通讯作者: Hemani G