and environmental influences (e.g., social ties and support, family stress, work conditions, community supports).

Equally important is the need to integrate these biological, behavioral, psychological, and social precursors to disease. The importance of such long-term developmental integration has recently been underscored by Worthman (1999): “We do not have an integrated model of human developmental physiology that can assist us in thinking about how ontogenetic changes may mediate environmental effects on adult health outcomes.” Emphasis on temporally distant and integrated assessment of psychological, social, and behavioral risk requires counterpart assessment of cumulative risk across multiple physiological systems, a topic that is addressed below.

Building on the guiding theme of integrative research (see Introduction), there is a need to assess physiological risk across multiple systems simultaneously. Illustrative of this objective is the broad framework of allostatic load (McEwen, 1998; McEwen and Stellar, 1993; McEwen and Seeman, 1999), which maintains that either repeated or continuous exposure to challenge or chronic underexposure and social isolation disrupts basic biological regulatory processes central to the maintenance of homeostasis and health. This model suggests that individuals (human or animal) exposed to challenge at vulnerable times (e.g., during early stages of pre-and postnatal development) or repeatedly during any period of life may experience overexposure to physiological responses that are outside normal operating ranges. Such overexposure comes about either because there are many challenges or because the turning on and turning off of the physiological responses is inefficient. This exacts a wear and tear termed “allostatic load.” Factors that may increase allostatic load include genetic predispositions, adverse experiences from early development, poor health behaviors (e.g., diet, exercise, and substance abuse), and exposure to stressful environmental conditions across the life span.

Through repeated efforts to adapt to stressful circumstances, the organism experiences a cumulative multisystem physiological toll, leading to cascading, potentially irreversible interactions between genetic predispositions and environmental factors. Over time, these cascades can contribute to large individual differences in dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, impaired immune function, altered cardiovascular reactivity, and ultimately stress-related physical and mental disorders (including chronic hypertension, coronary heart disease, diabetes, hippocampal atrophy and associated cognitive dysfunction; see Seeman et al.,