2001
DOI: 10.1046/j.1365-2826.2001.00601.x
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Prenatal Stress, Glucocorticoids and the Programming of the Brain

Abstract: A large body of human epidemiological data, as well as experimental studies, suggest that environmental factors operating early in life potently affect developing systems, permanently altering structure and function throughout life. This process with its persistent organizational effects has been called`programming'. The brain is a key target for such effects. This review focuses on the effects of adverse early environments, notably exposure to stress or glucocorticoids, upon subsequent adult hypothalamus-pitu… Show more

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Cited by 595 publications
(616 citation statements)
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References 220 publications
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“…Our results reinforce the fact that brain development is among the processes most vulnerable to glucocorticoids, with disruption of cell acquisition and differentiation achieved at concentrations well below those required for therapeutic interventions. The demonstration of these actions in neural cell cultures, reproducing all the essential findings from glucocorticoid treatment in vivo (Bohn, 1984;Fuxe et al, 1994Fuxe et al, , 1996Gilad et al, 1998;Gould et al, 1997;Kreider et al, 2005aKreider et al, , b, 2006Maccari et al, 2003;Matthews, 2000;Matthews et al, 2002;McEwen, 1992;Meaney et al, 1996;Weinstock, 2001;Welberg and Seckl, 2001), indicates that disrupted neurodevelopment is a direct glucocorticoid effect, not secondary to growth impairment, neuroendocrine disruption or other confounding actions in the fetus, neonate or mother. The successful prevention of respiratory distress in tens of thousands of preterm infants annually in the USA needs to be balanced against the adverse effects on brain development in the hundreds of thousands of individuals that receive the treatment.…”
Section: Discussionmentioning
confidence: 70%
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“…Our results reinforce the fact that brain development is among the processes most vulnerable to glucocorticoids, with disruption of cell acquisition and differentiation achieved at concentrations well below those required for therapeutic interventions. The demonstration of these actions in neural cell cultures, reproducing all the essential findings from glucocorticoid treatment in vivo (Bohn, 1984;Fuxe et al, 1994Fuxe et al, , 1996Gilad et al, 1998;Gould et al, 1997;Kreider et al, 2005aKreider et al, , b, 2006Maccari et al, 2003;Matthews, 2000;Matthews et al, 2002;McEwen, 1992;Meaney et al, 1996;Weinstock, 2001;Welberg and Seckl, 2001), indicates that disrupted neurodevelopment is a direct glucocorticoid effect, not secondary to growth impairment, neuroendocrine disruption or other confounding actions in the fetus, neonate or mother. The successful prevention of respiratory distress in tens of thousands of preterm infants annually in the USA needs to be balanced against the adverse effects on brain development in the hundreds of thousands of individuals that receive the treatment.…”
Section: Discussionmentioning
confidence: 70%
“…First, glucocorticoid use in preterm labor could contribute directly to adverse neurobehavioral outcomes, over and above the confounds of preterm delivery or of secondary effects on the maternalfetal unit, maternal-neonatal interactions, or maternal or offspring neuroendocrine function. Second, the wide window of vulnerability of neurodevelopment to disruption by DEX means that adverse effects, such as those already noted for glucocorticoid administration in vivo (Bohn, 1984;Fuxe et al, 1994Fuxe et al, , 1996Gilad et al, 1998;Gould et al, 1997;Kreider et al, 2005aKreider et al, , b, 2006Maccari et al, 2003;Matthews, 2000;Matthews et al, 2002;McEwen, 1992;Meaney et al, 1996;Weinstock, 2001;Welberg and Seckl, 2001), are likely to be exerted at any stage in the period of 24-34 weeks of gestation in which these agents are recommended for use (Gilstrap et al, 1995). Third, the targeting of multiple stages of neurodevelopment means that the net outcome will differ according to the maturational timetable for neurogenesis and differentiation in each brain region (Bayer et al, 1993).…”
Section: Discussionmentioning
confidence: 99%
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“…54,55 The involvement of HPAA might also account for the marked sex differences in our data as the patterns of programming of HPAA and autonomic responses are highly sex specific in many species. 56 There are a few limitations to our study. Although the determination of gestational age by the date of last menstrual period has been validated against fetal ultrasound, 57 it may introduce inaccuracy and thus any potential effect relating to gestational age has to be robust and statistically strong.…”
Section: Discussionmentioning
confidence: 94%
“…One of the underlying mechanisms is termed as 'fetal programming', which occurs when the normal pattern of fetal development is disrupted by an abnormal stimulus or insult at critical time points (6;8). Excessive glucocorticoids following stress in pregnant mothers may have such a programming effect on brain development (6)(7)(8)(9). In epidemiological studies, prenatal stress has been linked to congenital malformations (10), cerebral palsy (11), and psychiatric disorders including schizophrenia (12;13).…”
Section: LImentioning
confidence: 99%