A population-based cohort of 18,101 men and women aged 40–79 years who completed a measure of fatigue (Short Form 36 vitality domain, SF36-VT) in addition to providing information on possible confounding factors (age, sex, body mass index, marital status, smoking, education level, alcohol consumption, social class, depression, bodily pain, diabetes, use of β blockers, physical activity and diet) and mechanisms (haemoglobin, C-reactive protein and thyroid function) were followed up prospectively for up to 20 years. This evidence concerns the gene CRP and major depressive disorder.