Fatigue with up- vs downregulated brain arousal should not be confused

Fatigue is considered to be an important and frequent factor in motivation problems. However, this term lacks clinical and pathophysiological validity. Semantic precision has to be improved. Lack of drive and tiredness with increased sleepiness as observed in fatigue in the context of inflammatory and immunological processes (hypoaroused fatigue) has to be separated from inhibition of drive and tiredness with prolonged sleep onset latency as observed in major depression (hyperaroused fatigue). Subjective experiences as reported by patients, as well as clinical, behavioral, and neurobiological findings support the validity and importance of this distinction. A practical clinical procedure for how to separate hypo- from hyperaroused fatigue will be proposed.