Department of Public Health and Primary Care, Faculty of Medicine, Epidemiology Research Center, KU Leuven-University of Leuven, Leuven, Belgium.
Pediatr Res. 2022 Mar;91(4):757-770. doi: 10.1038/s41390-021-01435-4. Epub 2021 Mar 5.
Mental or neuropsychiatric disorders are widespread within our societies affecting one in every four people in the world. Very often the onset of a mental disorder (MD) occurs in early childhood and substantially reduces the quality of later life. Although the global burden of MDs is rising, mental health care is still suboptimal, partly due to insufficient understanding of the processes of disease development. New insights are needed to respond to this worldwide health problem. Next to the growing burden of MDs, there is a tendency to postpone pregnancy for various economic and practical reasons. In this review, we describe the current knowledge on the potential effect from advanced paternal age (APA) on development of autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder, and Tourette syndrome. Although literature did not clearly define an age cut-off for APA, we here present a comprehensive multifactorial model for the development of MDs, including the role of aging, de novo mutations, epigenetic mechanisms, psychosocial environment, and selection into late fatherhood. Our model is part of the Paternal Origins of Health and Disease paradigm and may serve as a foundation for future epidemiological research designs. This blueprint will increase the understanding of the etiology of MDs and can be used as a practical guide for clinicians favoring early detection and developing a tailored treatment plan. Ultimately, this will help health policy practitioners to prevent the development of MDs and to inform health-care workers and the community about disease determinants. Better knowledge of the proportion of all risk factors, their interactions, and their role in the development of MDs will lead to an optimization of mental health care and management. IMPACT: We design a model of causation for MDs, integrating male aging, (epi)genetics, and environmental influences. It adds new insights into the current knowledge about associations between APA and MDs. In clinical practice, this comprehensive model may be helpful in early diagnosis and in treatment adopting a personal approach. It may help in identifying the proximate cause on an individual level or in a specific subpopulation. Besides the opportunity to measure the attributed proportions of risk factors, this model may be used as a blueprint to design prevention strategies for public health purposes.
精神或神经精神障碍在我们的社会中广泛存在，影响着世界上每四个人中的一个。精神障碍（MD）的发作通常发生在儿童早期，并大大降低了后期生活的质量。尽管 MD 的全球负担正在增加，但精神保健仍然不尽人意，部分原因是对疾病发展过程的理解不足。需要新的见解来应对这一全球健康问题。除了 MD 的负担不断增加之外，由于各种经济和实际原因，人们也倾向于推迟怀孕。在这篇综述中，我们描述了目前关于高龄父亲（APA）对自闭症谱系障碍、精神分裂症、注意缺陷/多动障碍、双相情感障碍、强迫症和妥瑞氏综合征发展的潜在影响的知识。尽管文献没有明确界定 APA 的年龄截止点，但我们在这里提出了一个综合的多因素模型，用于 MD 的发展，包括衰老、新生突变、表观遗传机制、心理社会环境和选择进入晚育。我们的模型是健康与疾病的父系起源范式的一部分，可以作为未来流行病学研究设计的基础。这个蓝图将增加对 MD 病因的理解，并可作为临床医生的实用指南，有利于早期发现和制定个性化的治疗计划。最终，这将有助于卫生政策制定者预防 MD 的发生，并向卫生保健工作者和社区宣传疾病决定因素。更好地了解所有危险因素的比例、它们的相互作用及其在 MD 发展中的作用，将导致精神保健和管理的优化。
我们设计了一个 MD 因果模型，整合了男性衰老、（表观遗传学）和环境影响。它为 APA 与 MD 之间的关联的现有知识增加了新的见解。在临床实践中，这种综合模型在早期诊断和采用个性化方法的治疗中可能会有所帮助。它可以帮助在个体层面或特定亚人群中识别近端原因。除了有机会测量危险因素的归因比例外，该模型还可用于设计公共卫生目的的预防策略。
