Objective: Motor changes in major depression (MD) may represent potential markers of treatment response. Physiological rhythms (heart rate/gait cycle/hand movements) have been recently shown to be neither random nor regular but to display a fractal temporal organisation, possibly reflecting a unique central "internal clock" control. Sleep and mood circadian rhythm modifications observed in MD also suggest a role for this "internal clock". We set out to examine the fractal pattern of motor activity in MD. Methods: Ten depressed patients (46 +/- 20 years) and ten age- and gender-matched healthy controls (48 +/- 21 years) underwent a 6-h ambulatory monitoring of spontaneous hand activity with a validated wireless device. Fractal scaling exponent (alpha) was analysed. An a value close to 1 means the pattern is fractal. Results: Healthy controls displayed a fractal pattern of spontaneous motor hand activity (alpha: 1.0 +/- 0.1), whereas depressed patients showed an alteration of that pattern (alpha:1.2 +/- 0.15, p < 0.01), towards a smoother organisation. Conclusion: The alteration of fractal pattern of hand activity by depression further supports the role of a central internal clock in the temporal organisation of movements. This novel way of studying motor changes in depression might have an important role in the detection of endophenotypes and potential predictors of treatment response. (C) 2012 Elsevier Ireland Ltd. All rights reserved.