Placebo Effect on the Circadian Rhythm Period ? of Temperature and Hand-Grip Strength Rhythms: Interindividual and Gender-Related Difference

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Abstract
Two different medications, one assumed to be a tranquilizer and the other an antifatigue agent, were tested. Both were found to be ineffective and thus were viewed as placebos and named P1 and P2. The effect of P1 and P2 on the circadian rhythms of a set of variables (e.g., sleep/wake, oral temperature and grip strength of both hands) were monitored by five to 10 measurements per day over three consecutive 8- to 10-day spans. The first documented span was a control (no medication), and the second and third spans (in randomized order) were under P1 and P2. Healthy subjects volunteered for the studies: nine men and seven women (median age 28 years) in study 1 and 12 men and 12 women (median age 36 years) in study 2. They were synchronized with diurnal activity from 07:00 h (±30 min) to 00:00 h (± 1 h) and nocturnal rest. De Prins' method was used to obtain the prominent period τ in each (control, P1, and P2) individual time series. The χ2 test was used to test group and subgroup differences. All 40 subjects exhibited a significant sleep/wake rhythm with a ± = 24 h in control, P1, and P2 series. During the control span a gender-related statistically significant difference was observed: fewer men than women exhibited a temperature rhythm desynchronized from 24 h. In addition, more women than men had a τ < 24 h during control. The gender-related difference was obliterated by placebos. Similarly desynchronized circadian rhythms of left and right hand-grip strength were observed in both men and women during the control span, which were all obliterated by placebo but only in men. Results are discussed with regard to a genetic model of human dyschronism as proposed by the authors.