Purpose: Our study examined whether mindfulness-based stress reduction (MBSR) is noninferior to cognitive behavioral therapy for insomnia (CBT-I) for the treatment of insomnia in patients with cancer. Patients and Methods: This was a randomized, partially blinded, noninferiority trial involving patients with cancer with insomnia recruited from a tertiary cancer center in Calgary, Alberta, Canada, from September 2008 to March 2011. Assessments were conducted at baseline, after the program, and after 3 months of follow-up. The noninferiority margin was 4 points measured by the Insomnia Severity Index. Sleep diaries and actigraphy measured sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency. Secondary outcomes included sleep quality, sleep beliefs, mood, and stress. Results: Of 327 patients screened, 111 were randomly assigned (CBT-I, n = 47; MBSR, n = 64). MBSR was inferior to CBT-I for improving insomnia severity immediately after the program (P = .35), but MBSR demonstrated noninferiority at follow-up (P = .02). Sleep diary–measured SOL was reduced by 22 minutes in the CBT-I group and by 14 minutes in the MBSR group at follow-up. Similar reductions in WASO were observed for both groups. TST increased by 0.60 hours for CBT-I and 0.75 hours for MBSR. CBT-I improved sleep quality (P < .001) and dysfunctional sleep beliefs (P < .001), whereas both groups experienced reduced stress (P < .001) and mood disturbance (P < .001). Conclusion: Although MBSR produced a clinically significant change in sleep and psychological outcomes, CBT-I was associated with rapid and durable improvement and remains the best choice for the nonpharmacologic treatment of insomnia.
Circadian rhythms in several species can be phase-shifted by procedures that stimulate locomotor activity (“exercise”) during the usual sleep period. The role of arousal or sleep loss, independent of activity, in this effect has not been adequately resolved. We show here, using the sleep deprivation procedure of gentle handling, that comparably large phase shifts (up to 240 min advances) of the rest–activity cycle can be induced in Syrian hamsters by 3 hr of behavioral arousal, with minimal locomotion, beginning 6 hr before the usual active period. Horizontal distance traveled during the deprivation procedure averaged ∼0.08 km, compared to 2.5 km typical in exercise studies. Hamsters requiring fewer interventions exhibited larger shifts, suggesting that the level or continuity of spontaneous arousal determines shift size. The circadian rhythm of light-induced c-fos expression in the suprachiasmatic nucleus (SCN) was used as a phase marker to further demonstrate that the clock is reset within 1 hr after a 3 hr deprivation. Sleep deprivation mimicked the effects of exercise on basal c-fos expression in two components of the circadian system, suppressing basal Fos immunoreactivity in the SCN, and increasing Fos in the intergeniculate leaflet. Sleep deprivation without exercise in hamsters can rapidly reset the circadian clock and alter gene expression within the circadian system.
Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable.