Purpose
In this study, we investigate whether prospective associations between psychopathology, physical activity, and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) observed in the 1946 and 1970 birth cohorts were replicable in the 1958 British birth cohort.

Methods
Prospective study using the 1958 British birth cohort, which included 98.7% of births from 1 week in March 1958 in England, Wales, and Scotland. The outcome was self-reported CFS/ME by the age of 42 years, at which point 11,419 participants remained in the study. Psychopathology was assessed by the Rutter scales in childhood and the Malaise Inventory in adulthood. Physical activity was reported by the cohort member, mother and teacher in childhood and adulthood.

Results
The prevalence of CFS/ME was 1.0% (95% confidence interval [CI] = 0.9–1.3) and the median age of onset was 34 years. Premorbid psychopathology at 23 years (odds ratio [OR] = 1.85, 95% CI = 1.06–3.22) and 33 years (OR = 2.81, 95% CI = 1.28–6.18) significantly increased the odds of developing CFS/ME, supporting the 1946 cohort findings. Childhood psychopathology, sedentary behavior in childhood, and persistent exercise in adulthood were not associated with CFS/ME.

Conclusions
In cohort studies premorbid psychopathology in adulthood is a replicated risk marker for CFS/ME, whereas premorbid extremes of physical activity are not.