A CONSIDERABLE NUMBER OF STUDIES HAVE INDICATED THAT MAJOR DEPRESSIVE DISORDER (MDD) is characterized by difficulties initiating and maintaining sleep, increased stage 1 sleep, an early onset of rapid eye movement (REM) sleep, increased phasic REM activity, and a reduction in slow-wave (stage 3-4) sleep (cf. 1). However, a recent meta-analysis has indicated that no single sleep variable reliably differentiates depressed patients from healthy controls. 2 Moreover, not all studies, particularly more recent work, have shown significant differences between patients and controls. 3-4 Short REM latency (<65 minutes) and/or reduced slow-wave (SW) sleep, for example, are only present in 40%-60% of outpatients with MDD. As suggested recently, it is very likely that confounds such as age and sex have contributed to discrepant outcomes in sleep studies of MDD, most notably with regard to slow-wave sleep and measures of delta EEG activity (cf. 3-5). This issue is a key focus of the present paper.Work on REM and SW sleep abnormalities has led to speculation that sleep regulatory processes are disrupted in MDD. Specifically, the regulatory disturbance has been postulated as one of REM disinhibition, due to an imbalance in cholinergic-aminergic neurotransmitters that leads to both the early onset of REM and increased phasic REM activity. 6 There is fairly strong evidence that MDD is associated with increased cholinergic sensitivity using critical REM induction tests. To date, there is little evidence to refute this theory of sleep disturbance in MDD, although cholinergic sensitivity may not be specific to depression. 4 Others have suggested that the circadian oscillator that controls temperature, neuroendocrine function, and REM sleep is phase-advanced relative to SW sleep. 7-8 More recent evidence indicates that MDD is more likely to be associated with blunted amplitude circadian rhythms, 9Study Objectives: The primary aim was to evaluate group and sex differences in delta activity across non-rapid eye movement (NREM) sleep in depressed patients and healthy controls. Design: Repeated-measures ANOVA contrasted delta power, amplitude and incidence in the first three NREM periods (stages 2,3, and 4) of sleep. The time course of delta activity was evaluated with exponential regressions. Age effects on delta were evaluated with linear regression analysis. Setting: Two consecutive nights were spent in the laboratory, the first of which served as adaptation. Patients or Participants: Twenty-two (9 men, 13 women) symptomatic, but unmedicated, outpatients with major depressive disorder (MDD) and 23 healthy controls (15 men, 8 women) participated in the study. Measurements and Results: Delta power and amplitude showed significant group by sex interactions. Men with MDD showed lower power and amplitude in NREM sleep compared to women with MDD, but did not differ significantly from controls. However, the time course of delta power and amplitude was significantly different in men with MDD, with lower accumulation and slower dissipation ac...