Non-REM sleep in major depressive disorder

Abstract

Disturbed sleep is a key symptom in major depressive disorder (MDD). REM sleep alterations are well described in the current literature, but little is known about non-REM sleep alterations. Additionally, sleep disturbances relate to a variety of cognitive symptoms in MDD, but which features of non-REM sleep EEG contribute to this, remains unknown. We comprehensively analyzed non-REM sleep EEG features in three independently collected datasets (N=284). These included MDD patients with a broad age range, varying duration and severity of depression, unmedicated or medicated, age- and gender-matched to healthy controls. We explored changes in sleep architecture including sleep stages and cycles, spectral power, sleep spindles, slow waves (SW), and SW-spindle coupling. Next, we analyzed the association of these sleep features with acute measures of depression severity and overnight consolidation of procedural memory. Overall, no major systematic alterations in non-REM sleep architecture were found in patients compared to controls. For the microstructure of non-REM sleep, we observed a higher spindle amplitude in unmedicated patients compared to controls, and after the start of antidepressant medication longer SWs with lower amplitude and a more dispersed SW-spindle coupling. In addition, long-term, but not short-term medication seemed to lower spindle density. Overnight procedural memory consolidation was impaired in medicated patients and associated with lower sleep spindle density. Our results suggest that alterations in non-REM sleep EEG might be more subtle than previously reported. We discuss these findings in the context of antidepressant medication intake and age.

Increased Aperiodic Neural Activity During Sleep in Major Depressive Disorder

“…Intriguingly, whereas some polysomnographic studies have confirmed subjective sleep complaints of the patients by reporting decreased slow-wave and delta amplitudes, higher spindle amplitude, lower spindle density, and a more dispersed slow-wave-spindle coupling, others have suggested that oscillatory changes in MDD might be more subtle ( 5 , 6 ). One of the possible explanations for the divergent oscillatory findings is the confounding effect of aperiodic (i.e., non-oscillatory, scale-free) activity ( 7 , 8 , 9 ).…”

Increased aperiodic neural activity during sleep in major depressive disorder

“…Finally, it is important to note that in our previous study, we could not detect differences in the total (i.e., non-differentiated to its components) spectral power between unmedicated patients and controls (5). Taken together our recent and current reports demonstrate that in unmedicated patients with MDD, impaired sleep might be related to altered aperiodic activity specifically.…”

“…The demographic, clinical, and sleep characteristics of the participants are reported in our previous paper, where this dataset is referred to as “Dataset B” (5).…”

“…We retrospectively analyzed polysomnographic recordings from a previous study conducted at the Max Planck Institute of Psychiatry, Munich, Germany (5). The sample consisted of 40 patients with MDD and 40 healthy controls individually matched by age (±2 years of tolerance) and gender (See reference 5 for details).…”

“…Understanding the mechanisms of these alterations might bring new insights into the understanding of MDD. Intriguingly, whereas some polysomnographic studies confirm subjective sleep complaints of the patients by reporting decreased slow-wave and delta amplitudes, higher spindle amplitude, lower spindle density, and a more dispersed slow-wave-spindle coupling, others suggest that electroencephalographic (EEG) changes in MDD might be more subtle (4,5). Thus far, however, EEG analysis in MDD has been limited to neural oscillations whereas aperiodic (i.e., nonoscillatory, 1/f) dynamics have not been explored.…”