Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic, Barcelona, Spain; Institute of Biomedical Research Agusti Pi iSunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain.
Centre for Global Health, Trinity College Dublin, Dublin, Ireland; Department of Psychology, Trinity College Dublin, Dublin, Ireland; School of Medicine, Trinity College Dublin, Dublin, Ireland.
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jul 13;101:109910. doi: 10.1016/j.pnpbp.2020.109910. Epub 2020 Mar 4.
The fetal origin of adult disease hypothesis postulates that a stressful in utero environment can have deleterious consequences on fetal programming, potentially leading to chronic disease in later life. Factors known to impact fetal programming include the timing, intensity, duration and nature of the external stressor during pregnancy. As such, dynamic modulation of fetal programming is heavily involved in shaping health throughout the life course, possibly by influencing metabolic parameters including insulin action, hypothalamic-pituitary-adrenal activity and immune function. The ability of prenatal insults to program adult disease is likely to occur as a result of reduced functional capacity in key organs-a "thrifty" phenotype-where more resources are re-allocated to preserve critical organs such as the brain. Notably, it has been postulated that the manifestation of neuropsychiatric disorders in individuals priorly exposed to prenatal stress may arise from the interaction between hereditary factors and the intrauterine environment, which together precipitate disease onset by disrupting the trajectory of normal brain development. In this review we discuss the evidence linking prenatal programming to neuropsychiatric disorders, mainly schizophrenia, via a "Thrifty psychiatric phenotype" concept. We start by outlining the conception of the thrifty psychiatric phenotype. Next, we discuss the convergence of potential mechanistic pathways through which prenatal insults may trigger epigenetic changes that contribute to the increased morbidity and early mortality observed in neuropsychiatric disorders. Finally, we touch on the public health importance of fetal programming for these disorders. We conclude by providing a brief outlook on the future of this evolving field of research.
成人疾病的胎儿起源假说假设，宫内环境的压力可以对胎儿的发育产生有害影响，潜在地导致以后生活中的慢性疾病。已知影响胎儿发育的因素包括怀孕期间外部应激源的时间、强度、持续时间和性质。因此，胎儿发育的动态调节在塑造整个生命过程中的健康方面起着重要作用，可能通过影响代谢参数，包括胰岛素作用、下丘脑-垂体-肾上腺活性和免疫功能。产前损伤导致成人疾病的能力可能是由于关键器官的功能能力下降所致，即“节俭”表型，更多的资源被重新分配以保护大脑等重要器官。值得注意的是，有人假设先前暴露于产前应激的个体中神经精神障碍的表现可能是遗传因素和宫内环境相互作用的结果，这种相互作用通过破坏正常大脑发育的轨迹引发疾病的发生。在这篇综述中，我们通过“节俭的精神表型”概念讨论了将产前编程与神经精神障碍（主要是精神分裂症）联系起来的证据。我们首先概述了节俭的精神表型的概念。接下来，我们讨论了潜在的机制途径的趋同，通过这些途径，产前损伤可能引发表观遗传变化，导致神经精神障碍中观察到的发病率增加和早期死亡率。最后，我们提到了胎儿编程对这些疾病的公共卫生重要性。我们最后简要展望了这一不断发展的研究领域的未来。
