Fatigue is a common problem; when chronic and disabling, subjects can be categorized as having chronic fatigue syndrome (CFS). Whilst it is most likely a multifactorial condition of biopsychosocial origin, the nature of the pathophysiological component remains unclear. There has been a wealth of interest in the possible hypothalamo–pituitary–adrenal (HPA) axis dysfunction in CFS, and whether such changes may mediate fatigue. On balance, there appears to be reduced cortisol output in a proportion of patients, together with heightened negative feedback and glucocorticoid receptor function. There is evidence for impaired adrenocorticotropic hormone (ACTH) and cortisol responses to a variety of challenges. However, there is no evidence for a specific or uniform dysfunction of the HPA axis. Evidence that these changes may be related to symptom production comes from randomized controlled trials of glucocorticoid replacement therapy, which have shown improvements in fatigue and disability. Given the many factors that may impinge on the HPA axis in CFS, such as inactivity, sleep disturbance, psychiatric comorbidity, medication and ongoing stress, it seems likely that there is not a single or specific change to the HPA axis in CFS and that the observed HPA axis disturbances are of multifactorial etiology. This is further supported by a comparison of neuroendocrine findings in other conditions in which fatigue is prominent, showing both similarities and differences with the pattern in CFS.

Neuroendocrine system plays an important role in modulating our body functions and emotions. At the same time, emotions implicate a pivotal role in the regulation of brain function and neuroendocrine system. Negative affective states such as depression and stress are associated with premature mortality and increase the risk of various fatal diseases. It has been suggested that positive affective states are protective and improve our health and productiveness. Several potential mechanisms have been posited to account for these associations including improved health behaviour, direct physiological benefits, enhanced resistance and recovery from stress among individuals with high versus low positive emotional resources. This review summarises information concerning the neuronal and hormonal systems in mood, impact of negative and positive affective states on the level of cortisol, epinephrine, serotonin, dopamine and endorphins. The functional correlation of neuronal and hormonal systems in the development of diseases and their ability to enhance health-relevant biological processes are also evaluated.