Scientific Investigations
EEG Power Spectra Response to a 4-h Phase Advance and Gaboxadol Treatment in 822 Men and Women
http://dx.doi.org/10.5664/jcsm.1316
Junshui Ma, Ph.D.1; Derk-Jan Dijk, Ph.D.2; Vladimir Svetnik, Ph.D.1; Yevgen Tymofyeyev, Ph.D.1; Shubhankar Ray, Ph.D.1; James K. Walsh, Ph.D.3,4; Steve Deacon, Ph.D.5
1Merck Research Laboratories, Biometrics Research, Rahway, NJ; 2Surrey Sleep Research Centre, University of Surrey, Guildford, UK; 3St. Johns and St. Lukes Hospitals, St. Louis, MO; 4Department of Psychology, St. Louis University, St. Louis, MO; 5H. Lundbeck A/S, Valby, Denmark
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.
Citation:
Ma J; Dijk DJ; Svetnik V; Tymofyeyev Y; Ray S; Walsh JK; Deacon S. EEG power spectra response to a 4-h phase advance and gaboxadol treatment in 822 men and women. J Clin Sleep Med 2011;7(5):493-501.
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