Neuroendocrine and Immune Contributors to Fatigue

Silverman, Marni N.; Heim, Christine M.; Nater, Urs M.; Marques, Andrea H.; Sternberg, Esther M.

doi:10.1016/j.pmrj.2010.04.008

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Volume 2, Issue 5 , Pages 338-346, May 2010

Neuroendocrine and Immune Contributors to Fatigue

Marni N. Silverman, PhD
- Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, Rockville, MD^†
Christine M. Heim, PhD
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA^‡
Urs M. Nater, PhD
- Department of Clinical Psychology and Psychotherapy, University of Zurich, Switzerland, Centers for Disease Control and Prevention, Atlanta, GA^§
Andrea H. Marques, MD, PhD
- Genetic Epidemiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD^∥
Esther M. Sternberg, MD
- Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, Integrative Neural Immune Program, 5625 Fishers Lane (MSC-9401), Rockville, MD 20852^¶
- Address correspondence to E.M.S.

Abstract

Central fatigue, a persistent and subjective sense of tiredness, generally correlates poorly with traditional markers of disease. It is frequently associated with psychosocial factors, such as depression, sleep disorder, anxiety, and coping style, which suggest that dysregulation of the body's stress systems may serve as an underlying mechanism in the maintenance of chronic fatigue (CF). This article addresses the endocrine, neural, and immune factors that contribute to fatigue and describes research regarding the role of these factors in chronic fatigue syndrome as a model for addressing the biology of CF. In general, hypoactivity of the hypothalamic-pituitary-adrenal axis, autonomic nervous system alterations characterized by sympathetic overactivity and low vagal tone, as well as immune abnormalities, may contribute to the expression of CF. Noninvasive methods for evaluating endocrine, neural, and immune function are also discussed. Simultaneous evaluation of neuroendocrine and immune systems with noninvasive techniques will help elucidate the underlying interactions of these systems, their role in disease susceptibility, and progression of stress-related disorders.