symptoms depends on the degree of activity of the peripheral signals and how they are modulated by the CNS in the face of stress or other modifying factors.

That model can be generalized to include other medical conditions. Most people with fibromyalgia, chronic fatigue, or other pain syndromes will have milder symptoms because their dysfunction is mostly peripheral, with little input from the CNS. But patients with more severe symptoms, greater symptom reporting, greater psychosocial disturbance, and poorer health status and quality of life will have greater CNS contributions to their symptoms. With increasing CNS dysregulation, the ability to filter incoming peripheral and visceral signals is impaired, and a person will report more symptoms (Chang et al. 2003; Clauw and Chrousos 1997; Sternberg 1995); this helps to explain the clinical similarity of those conditions when they are severe.


The stress response, the body’s reaction to stress, can be life-saving (and be adaptive) in the short term when a person confronts immediate stressors but can lead to illness or disease (and be maladaptive) in the long term when stressors are severe, recurrent, or persistent. In response to deployment-related stress, physiologic changes occur in the body, may persist for a long time after deployment has ended, and may result in symptoms and disorders that appear soon after exposure to the stressor or become evident only years later.

Some biologic factors and life experiences can modify a person’s response to stress, including genes, early-life events, and the degree to which the stressor is perceived to be controllable. Those factors might help to explain the differences in people’s reactions to stress and the development of subsequent health effects.

The studies discussed in this chapter provide a context for understanding why people deployed to a war zone may report more symptoms than people who are not deployed—the stress response results in a cascade of physiologic changes that can have profound effects on multiple organ systems. War-zone stressors might produce disruption in brain systems that mediate responses to stress and in central pain regulatory pathways that can result in greater reporting of physical and emotional symptoms. The continuation of altered physiologic states over months and years can contribute to the accumulation of a chronic stress burden that has adverse long-term health consequences. The possible long-term manifestations of those altered states in veterans are discussed in Chapters 5, 6, and 7.

Much progress has been made in understanding the physiologic mechanisms of the stress response, particularly in animal models, but work remains to be done in human studies. Research on the effect of stressors on the endocrine, immune, cardiovascular, and gastrointestinal systems demonstrates the complexity of the interactions between those systems.


Alheid GF, Heimer L. 1988. New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: The striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience 27(1):1-39.

Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF. 2005. Medial prefrontal cortex determined how stressor controllability affects behavior and dorsal raphe nucleus. Nature Neurosciences 8:365-371.

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