Early Life Stress Research
in the Mind-Body Program
Numerous studies have indicated that interactions between the central nervous
system (CNS) and the immune system play an important role in the maintenance of
homeostasis and the development of immunologic diseases including infectious
diseases, cancer and autoimmune disorders. One of the most well established
findings in the area of CNS-immune interactions is the profound impact of acute
and chronic stress on the immune response. Relevant pathways mediating these
effects of stress on the immune system include the hypothalamic-pituitary-adrenal
(HPA) axis and the sympathetic nervous system (SNS).
Given that HPA axis and SNS outflow pathways during stress are regulated by corticotropin
releasing factor (CRF), a number of studies have focused on the impact of CRF on the immune system.
Interestingly, in addition to causing suppression of both cell-mediated and humoral
immune function, CRF has been found to induce the release of several cytokines
including IL (interleukin)-1 and IL-6. These cytokines in turn have been shown
to stimulate CRF production/release and mediate a host of behavioral responses that
include “sickness behavior” with features that overlap with major depression.
Early life stress in humans and laboratory animals has been shown to augment
CRF activity with evidence that CRF pathways are sensitized to subsequent stressor
exposure in adulthood. Given the impact of CRF on the immune system and the potential
impact of the immune system on the CNS and CRF, examination of the potential
consequences and contributions of CRF-immune interactions to physical and emotional
health in individuals exposed to early life stress is a consideration of paramount importance.
The long term objectives of these studies are to further understand 1) how early
life stress impacts upon the adult immune system, 2) whether CRF is the major mediator
of the observed effects and 3) whether proinflammatory cytokines contribute to the
neurobiologic and immunologic features of early life stress.
The hypotheses are that 1) early life stress will enhance stress-induced activation
of proinflammatory cytokines and their signaling pathways, including NFkB and MAP
kinase, 2) increased activation of proinflammatory signaling pathways secondary to
early life stress will be mediated by CRF and its effects on the HPA axis and/or
SNS, and 3) activation of proinflammatory signaling pathways by IL-1 and IL-6 will
contribute to the neuroendocrine, behavioral and immunologic manifestations of early
Taken together, these studies will provide new insights into the pathophysiology
of early life stress and provide a foundation for the development of novel treatment
strategies for the neurobiologic and immunologic consequences of early life stress.
To learn more about active research studies, please click here.