Figure 1. Components of hypothalamic–pituitary–adrenal axis and serotonergic input; sites of negative feedback are shown with the – sign. CRH, corticotrophin-releasing hormone; ACTH, adrenocorticotrophic hormone; AVP, arginine vasopressin; MR, mineralocorticoid receptors; GR, glucocorticoid receptors; 5-HT, 5-hydroxytryptamine (serotonin); 5-HIAA, 5-hydroxyindoleacetic acid. Letters relate to the sites of proposed abnormalities in chronic fatigue syndrome, listed in Table 3.

Figure 2. Predisposing, precipitating and perpetuating factors in the generation of acute, subacute and chronic fatigue. The model separates those considered to be risk factors or triggers, and those that may be responsible for fatigue perpetuation in chronic fatigue syndrome. Factors interact substantially and may be more important in some patients than in others (e.g. chronic fatigue after viral infections is more likely with previous psychological disorder and prolonged convalescence). EBV, Epstein–Barr virus; 5-HT, 5-hydroxytryptamine (serotonin).

Figure 3. Time course of improvement in chronic fatigue syndrome during and after 13 sessions of either cognitive behavioural therapy (CBT) or relaxation therapy as a control intervention. (a) Disability, measured using the physical function subscale of the medical outcomes survey short form 36 (SF-36) (0 = maximum disability; 100 = no disability). (b) Fatigue, scored on a 13-item scale (13 = maximum fatigue; 0 = no fatigue). Pre, pretreatment; mid, midtreatment; post, posttreatment. Adapted from Deale A (1998).