Moog N K, Entringer S, Heim C, Wadhwa P D, Kathmann N, Buss C
Department of Medical Psychology, Charité University Medicine Berlin, Luisenstrasse 57, 10117 Berlin, Germany.
Department of Medical Psychology, Charité University Medicine Berlin, Luisenstrasse 57, 10117 Berlin, Germany; University of California, Irvine, Development, Health, and Disease Research Program, 333 The City Drive West, Suite 1200, Orange, CA 92868, USA; Department of Pediatrics, University of California, Irvine, School of Medicine, 505 South Main Street, Suite 525, Orange, CA 92868, USA.
Neuroscience. 2017 Feb 7;342:68-100. doi: 10.1016/j.neuroscience.2015.09.070. Epub 2015 Oct 3.
Thyroid hormones (THs) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence TH synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programing of brain development, with implications for early identification of risk, primary prevention and intervention.
甲状腺激素（THs）在大脑发育和成熟的许多基本过程中起着至关重要的作用。发育中的胚胎/胎儿依赖于母体提供的TH。胎儿甲状腺直到妊娠中期才开始合成TH，严重母体TH缺乏对后代神经发育的不良后果已得到充分证实。最近的证据表明，即使是更温和形式的母体甲状腺功能障碍，尤其是在妊娠早期，也可能对儿童认知发展和神经发育障碍风险产生持久影响。此外，这些观察到的改变在出生后似乎在很大程度上是不可逆的。因此，从其影响的性质、程度、时间特异性和背景特异性方面更好地了解母体甲状腺功能障碍对后代神经发育的作用非常重要。关于背景特异性问题，孕期母体应激和与应激相关的生物学过程可能会调节母体甲状腺功能。然而，迄今为止，在胎儿大脑发育背景下甲状腺与应激系统之间相互作用的可能性尚未得到探讨。我们在本综述开始时简要概述孕期TH生物学及其对发育中大脑影响的文献综述。接下来，我们考虑并讨论与母体应激和应激生物学相关的过程是否以及如何与母体甲状腺功能对后代大脑发育的影响相互作用并对其进行调节。我们综合了几个研究领域并确定了可能需要进一步研究的重要知识空白。本综述的科学和公共卫生相关性在于更好地理解大脑发育甲状腺编程的时间、机制和背景，对早期风险识别、一级预防和干预具有重要意义。
