Sleep Delta power, age, and sex effects in treatment-resistant depression

Abstract

Electroencephalographic (EEG) deficits in slow wave activity or Delta power (0.5-4 Hz) indicate disturbed sleep homeostasis and are hallmarks of depression. Sleep homeostasis is linked to restorative sleep and potential antidepressant response via non-rapid eye movement (NREM) slow wave sleep (SWS) during which neurons undergo essential repair and rejuvenation. Decreased Low Delta power (0.5-2 Hz) was previously reported in individuals with depression. This study investigated power levels in the Low Delta (0.5-<2 Hz), High Delta (2-4 Hz), and Total Delta (0.5-4 Hz) bands and their association with age, sex, and disrupted sleep in treatment-resistant depression (TRD). Mann-Whitney U tests were used to compare the nightly progressions of Total Delta, Low Delta, and High Delta in 100 individuals with TRD and 24 healthy volunteers (HVs). Polysomnographic parameters were also examined, including Total Sleep Time (TST), Sleep Efficiency (SE), and Wake after Sleep Onset (WASO). Individuals with TRD had lower Delta power during the first NREM episode (NREM1) than HVs. The deficiency was observed in the Low Delta band versus High Delta. Females with TRD had higher Delta power than males during the first NREM1 episode, with the most noticeable sex difference observed in Low Delta. In individuals with TRD, Low Delta power correlated with WASO and SE, and High Delta correlated with WASO. Low Delta power deficits in NREM1 were observed in older males with TRD, but not females. These results provide compelling evidence for a link between age, sex, Low Delta power, sleep homeostasis, and non-restorative sleep in TRD.

Keywords: Electroencephalography (EEG); High Delta; Low Delta; Non-restorative sleep; Polysomnography; Sleep homeostasis; Treatment-resistant depression.

Figure 1:

Differences in non-rapid eye movement (NREM1) Total Delta, Low Delta, and High Delta power between individuals with treatment-resistant depression (TRD; red) and healthy volunteers (HVs; blue). Box and whisker plot: y-axis represents Delta power spectral density range expressed in (micro) Volts^2 per Hertz. The upper and lower box edges show the first and third data quartiles, the whiskers show the data range, and outliers are indicated by black dots. The p-values show significant changes in Low, High, and Total Delta between HVs and individuals with TRD.

Figure 2:

Upper panel: Sex effects on Low Delta and High Delta power in individuals with treatment-resistant depression (TRD). (Left) NREM1 Low Delta in females (F, light gray) versus males (M, dark gray) with TRD. (Right) NREM1 High Delta (p<0.001). Lower panel: Age effects on High Delta and Low Delta power in NREM1 in individuals with TRD. (Left) Low Delta (p<0.0001). (Right) High Delta; (p=0.0043). The age range is displayed on the x-axis, while the y-axis represents Delta power spectral density expressed in (micro) Volts^2 per Hertz.

Figure 3:

Age vs Low Delta in females and males with treatment-resistant depression (TRD). Simple linear regression between age and Low Delta in female (light squares) and male (dark circles) individuals with TRD. The outcome variable was Low Delta (y axis), and the predictor was age (x axis) (F=4.855. DFn=1, DFd=96, p=0.030). Inset: Bar chart. Left: Low Delta in young (<30 yrs) females (n=15) (light bars) versus males (n=14) (dark bars). Right: Low Delta in older (>40 yrs) females (n=24) versus males (n=18), unpaired t-test, p=0.004.