source of nutrients for this development, and the interplay between the mother and the fetus is reflected in placental function. Demanding conditions experienced by the mother are transmitted to the fetus through endocrine and nutritional signals. These signals result in both short-term and long-term changes in gene expression in the fetus (Roberts and Redman, 1993; Wadhwa, 1998). Thus, the origins of adult disease are often found in prenatal life.

An example of this phenomenon, where behavioral characteristics of the mother are also relevant is interuterine growth retardation (IUGR; Sattar et al., 1999; de Onis et al., 1998, Gülmezouglu et al., 1997). It is estimated that genetic mutations account for approximately 10 percent of the cases of IUGR. The remainder of the cases are due to a wide range of environmental conditions, including maternal smoking, serious infection, malnutrition (especially protein deficiency), excessive alcohol consumption, abuse of drugs, and extreme maternal stress (Kramer, 1987a, b). Each of these risk factors is associated with increased risk of high levels of glucocorticoids in the mother. Glucocorticoids inhibit insulin-like growth factor (IGF) gene expression, as well as the action of IGF (de Kloet et al., 1998). They also increase the production of IGF-binding protein 1 (IGF-1), which serves to biologically inactivate IGF. Both conditions impair development and contribute to the emergence of IUGR. The alterations in gene expression accompanying IUGR increase the sensitivity of hypothalamic-pituitary-adrenal (HPA) and sympathetic responses to stress in later life (Ladd et al., 1996). The elevated levels of stress hormones, in turn, increase vulnerability of the individual to diabetes and heart disease. An important challenge for future research is to understand how psychosocial adversity over the life course of low-birth-weight babies—having experienced IUGR—is related to subsequent processes of gene expression that culminate in diabetes, coronary heart disease, or both.

PERSONAL TIES AND GENE EXPRESSION IN MIDLIFE

Increasing evidence documents the role of personal ties on gene expression in midlife. For example, the genetic transcription responsible for the production of lymphocyte growth hormone (L-GH) is, in part, age related, as L-GH secretion decreases with increasing age (Nordin and Proust, 1987; Krishnaraj et al., 1998). However, extended disruption of personal ties also modulates L-GH levels. Caregivers of spouses with Alzheimer's disease have markedly suppressed L-GH concentrations compared to age- and gender-matched controls (Wu et al., 1999). The transduction process by which disruption of personal ties modulates growth hormone (GH) messenger RNA (mRNA) is most likely to involve stress hormones such as adrenocoricotropic hormone (ACTH), cortisol, and catecholamines (Kiecolt-Glaser



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement