Antidepressant effects of selective slow wave sleep deprivation in major depression: A high-density EEG investigation

Abstract

Sleep deprivation can acutely reverse depressive symptoms in some patients with major depression. Because abnormalities in slow wave sleep are one of the most consistent biological markers of depression, it is plausible that the antidepressant effects of sleep deprivation are due to the effects on slow wave homeostasis. This study tested the prediction that selectively reducing slow waves during sleep (slow wave deprivation; SWD), without disrupting total sleep time, will lead to an acute reduction in depressive symptomatology. As part of a multi-night, cross-over design study, participants with major depression (non-medicated; n = 17) underwent baseline, SWD, and recovery sleep sessions, and were recorded with high-density EEG (hdEEG). During SWD, acoustic stimuli were played to suppress subsequent slow waves, without waking up the participant. The effects of SWD on depressive symptoms were assessed with both self-rated and researcher-administered scales. Participants experienced a significant decrease in depressive symptoms according to both self-rated (p = .007) and researcher-administered (p = .010) scales, while vigilance was unaffected. The reduction in depressive symptoms correlated with the overnight dissipation of fronto-central slow wave activity (SWA) on baseline sleep, the rebound in right frontal all-night SWA on recovery sleep, and the amount of REM sleep on the SWD night. In addition to highlighting the benefits of hdEEG in detecting regional changes in brain activity, these findings suggest that SWD may help to better understand the pathophysiology of depression and may be a useful tool for the neuromodulatory reversal of depressive symptomatology.

Introduction

Sleep disturbances are an integral part of the diagnostic criteria for major depression (American Psychiatric Association, 2000, Peterson and Benca, 2006), and sleep may provide biomarkers for treatment response to antidepressant medication (Steiger and Kimura, 2010). Since the initial investigation of a therapeutic benefit of sleep deprivation (SD) in depression (Pflug and Tölle, 1971), many studies have attempted to understand the link between sleep and depression. SD interventions, including total sleep deprivation (TSD), partial sleep deprivation and selective REM sleep deprivation (REMD) can acutely reverse depressive symptoms in approximately 50–60% of patients with major depression (Gillin, 1983, Wu and Bunney, 1990, Kuhs and Tölle, 1991, Wirz-Justice and Van den Hoofdakker, 1999, Hemmeter et al., 2010). Decreased REM sleep latency and increased REM density are hallmark features of depression (Kupfer and Foster, 1972, Benca et al., 1992). Given these features, and the observation of suppressed REM sleep with antidepressant medication (Riemann et al., 1990, Jobert et al., 1999), it has been postulated that selectively suppressing REM sleep may yield an antidepressant response (Vogel et al., 1975).

Slow wave sleep abnormalities, however, are also prominent in depression (Borbély and Wirz-Justice, 1982, Benca et al., 1992) and likely play a role in the modulation of depressive symptomatology. For instance, Nissen et al. (2001) found that a high delta sleep ratio (quotient of slow wave activity [SWA] in the first to the second NREM sleep cycle) on the night prior to SD predicted the antidepressant response. In addition, Duncan et al. (1980) showed that the participants who responded to SD treatment exhibited a greater rebound of slow wave sleep and total sleep time upon recovery sleep compared to their baseline. Finally, Borbély (1987) proposed that sleep in depression is characterized by abnormal slow wave homeostasis, which may be renormalized by SD therapy.

The current study directly investigated the role of slow wave homeostasis in the antidepressant action of SD by using a selective slow wave deprivation (SWD) technique. As the first study to assess the antidepressant effects of SWD in depression, this exploratory investigation had two primary aims. First, we sought to determine the efficacy of the SWD technique in suppressing SWA in depressed participants, to measure the overnight change in depressive symptomatology, and to examine the extent to which these two variables are correlated. Second, we aimed with this initial investigation, using a simple, randomized cross-over design, to provide the foundation for larger, more controlled, comparison-based, double-blinded studies to rigorously assess the usefulness of SWD in treating major depression.