Wadhwa Pathik D
Behavioral Perinatology Research Program, Department of Psychiatry and Human Behavior, College of Medicine, University of California, Irvine, 92697-4260, USA.
Psychoneuroendocrinology. 2005 Sep;30(8):724-43. doi: 10.1016/j.psyneuen.2005.02.004. Epub 2005 Apr 25.
Individual differences in psychoneuroendocrine function play an important role in health and disease. Developmental models postulate that these individual differences evolve through a progressive series of dynamic time-, place- and context-dependent interactions between genes and environments in fetal, infant and adult life. The effects of early experience have longer-lasting and more permanent consequences than those later in life. Experimental studies in animals have provided convincing evidence to support a causal role for stress-related psychoneuroendocrine processes in negatively influencing critical developmental and health outcomes over the life span, and have also offered valuable insights into putative physiological mechanisms. However, the generalizability of these findings from animals to humans may be limited by the existence of large inter-species differences in physiology and the developmental time-line. We have initiated a program of research in behavioral perinatology and conducted studies over the past several years to examine the effects of stress-related psychoneuroendocrine processes in human pregnancy on fetal developmental and health outcomes. Our findings support a significant and independent role for maternal prenatal stress in the etiology of prematurity-related outcomes, and suggest that these effects are mediated, in part, by the maternal-placental-fetal neuroendocrine axis, and specifically by placental corticotropin-releasing hormone. Our findings also suggest that the use of a fetal challenge paradigm offers a novel way to quantify fetal neurobehavioral maturity in utero, and that the maternal environment exerts a significant influence on the fetal neurodevelopmental processes related to recognition, memory and habituation. Finally, our findings provide preliminary evidence to support the notion that the influence of prenatal stress and maternal-placental hormones on the developing fetus may persist after birth, as assessed by measures of temperament and behavioral reactivity in the first few years of postnatal life. A description of this body of work is followed by the elucidation of questions for further research and a discussion of implications for life-span development and health.
心理神经内分泌功能的个体差异在健康与疾病中起着重要作用。发展模型假定，这些个体差异是通过胎儿期、婴儿期及成年期基因与环境之间一系列渐进的、动态的、依赖时间、地点和情境的相互作用而演变形成的。早期经历所产生的影响比生命后期的经历具有更持久、更深远的后果。动物实验研究提供了令人信服的证据，支持应激相关的心理神经内分泌过程在对整个生命跨度的关键发育和健康结果产生负面影响方面具有因果作用，同时也为推测的生理机制提供了有价值的见解。然而，由于生理和发育时间线方面存在较大的种间差异，这些动物研究结果向人类的推广可能会受到限制。我们启动了一项行为围产医学研究计划，并在过去几年中开展了多项研究，以探讨人类孕期应激相关的心理神经内分泌过程对胎儿发育和健康结果的影响。我们的研究结果支持母体产前应激在早产相关结局的病因学中具有重要且独立的作用，并表明这些影响部分是由母-胎-胎盘神经内分泌轴介导的，特别是通过胎盘促肾上腺皮质激素释放激素。我们的研究结果还表明，使用胎儿应激范式为量化子宫内胎儿神经行为成熟度提供了一种新方法，并且母体环境对与认知、记忆和习惯化相关的胎儿神经发育过程具有重大影响。最后，我们的研究结果提供了初步证据，支持这样一种观点，即产前应激和母-胎-胎盘激素对发育中胎儿的影响在出生后可能仍然存在，这一点通过出生后最初几年的气质和行为反应测量得以评估。在对这一系列工作进行描述之后，将阐明进一步研究的问题，并讨论其对寿命发展和健康的意义。
