Several studies tried to indentify predictors of response to sleep deprivation in order to clarify the mechanism of action. Among clinical predictors is a symptom pattern with "endogenous" or "melancholic" traits and the presence of pronounced diurnal variations of mood, and a behaviour pattern pointing to an elevated level of arousal or activity. Another predictor is a pronounced sleep disturbance during the baseline night. Among the many neuroendocrine and neurohumoral factors which have been studied, only elevated thyroid hormones turned out to be a predictor for response to sleep deprivation. PET and SPECT studies have convergently demonstrated an elevated metabolism in parts of the limbic system (e.g., the anterior cingulum) at baseline in responders. These findings do not yet allow conclusions with respect to the neurotransmitter systems involved.