EEG power spectra response to a 4-h phase advance and gaboxadol treatment in 822 men and women

Abstract

Study objective: To explore the effect of gaboxadol on NREM EEG in transient insomnia using power spectral analysis and evaluate the response between men and women.

Methods: This was a randomized, double-blind, 3-way, parallel-group transient insomnia study in 22 sleep laboratories. After a baseline night (N1), subjects underwent a 4-h phase-advance of their habitual sleep time the following night (N2). Healthy subjects aged 18-64 y were given single-blind placebo on N1 followed by double-blind treatment on N2 (gaboxadol 10 mg [n = 271], 15 mg [n = 274], or placebo [n = 277])

Results: At baseline, women showed significantly greater values in low frequency activity (< 10 Hz) and in high spindle/low beta frequency activity (14-18 Hz) compared to men. During the phase advance (placebo N2-baseline N1), there was a significant increase in power within the high spindle/low beta frequency range (15-17 Hz) and a significant reduction in beta activity (20-32 Hz), which was greater in women than men. Gaboxadol induced a significant (dose-related) increase in low frequencies (< 8 Hz) and a significant (dose-related) decrease within the alpha/spindle range (11-12 Hz). The effect was dependent upon sex, with a greater magnitude of effect observed in women than men.

Conclusion: Gaboxadol shows a characteristic NREM EEG spectral profile in a model of transient insomnia. Men and women show clear differences in NREM EEG activity at baseline, to gaboxadol treatment and to phase-shifts in habitual sleep/wake times. The exact mechanisms underlying the sex differences remain unclear, but sex is an important variable in studies evaluating sleep and gaboxadol. TRIAL REGISTRY INFORMATION:

Trial registry: www.clinicaltrials.gov, study identifier: NCT00102167.

Keywords: EEG power spectra; Gender differences; gaboxadol; slow wave sleep; transient insomnia.

Figure 1

Mean power spectra densities of women relative to men (men = 100%) for each frequency bin

Figure 2

Effect of a 4h phase advance on EEG power spectra (1Hz bins) (A) overall and (B) women (□) and men (▴) during 8h of NREM sleep

Figure 3

Effects of gaboxadol on the NREM sleep EEG power spectral densities (1Hz bins) during 8h of sleep after a 4h phase advance of subjects' habitual bedtimes for (A) combined sex (• 10mg, n = 247; ○ 15mg, n = 253) and (B) men and women separately (▴- - -▴ men 10mg, n = 94; ▴––▴men 15mg, n = 88; □- - -□ female 10mg, n = 153; □––□ female 15mg, n = 165)

Figure 4

Time course effects of gaboxadol across the night (per third) on NREM EEG power spectral densities (1Hz bins) during 8h of sleep after a 4h phase advance of subjects' habitual bedtimes for men and women (▴- - -▴ men 10mg, n = 94; ▴––▴men 15mg, n = 88; □- - -□ women 10mg, n = 153; □––□ women 15mg, n = 165)