Melatonin and Sleep Qualities in Healthy Adults: Pharmacological and Expectancy Effects

The impact of expectancy on melatonin's effects on sleep qualities was investigated. Both the pharmacological dose of 6 mg of melatonin and the expectation of receiving melatonin were predicted to improve subjective ratings of sleep qualities. The balanced placebo design varied 2 factors within-subjects: actual treatment and expected treatment. Adults (N = 53; 21 men and 32 women) between the ages of 26 and 71 years were administered either 6 mg of melatonin or a placebo for 8 nights. An instructional manipulation directed participants' expectations. Participants rated their nightly sleep experiences. Results revealed that feelings upon awakening differed between genders and that expecting melatonin increased ratings of sleep continuity. Most important, high ratings of “grogginess/tiredness” were associated with receiving melatonin, regardless of expectancy, as well as with receiving placebo when melatonin was expected. Overall, the findings underscore the need to consider expectancy and gender differences in research on melatonin and sleep experiences.     

Effects of intranasal oxytocin on 'compassion focused imagery'

This study explored the effects of oxytocin on Compassion Focused Imagery (CFI), that is, imagining another "mind" being deeply compassionate to oneself, and the interaction of these effects with self-criticism and feeling socially safe with others. Forty-four healthy participants (29 men and 15 women) completed self-report measures of self-criticism, attachment style, and social safeness before taking part in a double-blind randomized placebo controlled study. They attended two imagery sessions, receiving oxytocin in one and a placebo in the other. Positive affect was measured before and after each imagery session, and "imagery experience" was assessed after each session. Overall, oxytocin increased the ease of imagining compassionate qualities but there were important individual differences in how CFI was experienced. Participants higher in self-criticism, lower in self-reassurance, social safeness, and attachment security had less positive experiences of CFI under oxytocin than placebo, indicating that the effects of oxytocin on affiliation may depend on attachment and self-evaluative styles.     

Mood influences on acute smoking responses are independent of nicotine intake and dose expectancy

Acute responses to smoking are influenced by nicotine and by nonpharmacological factors such as nicotine dose expectancy and sensory effects of smoke inhalation. Because negative mood increases smoking reinforcement, the authors examined whether these effects may be altered by mood context. Smokers (n=200) participated in 2 sessions, negative or positive mood induction, and were randomized to 1 of 5 groups. Four groups comprised the 2x2 balanced placebo design, varying actual (0.6 mg vs. 0.05 mg yield) and expected nicotine dose (expected nicotine vs. denicotinized [denic]) of cigarettes. A fifth group was a no-smoking control. Smoking, versus not smoking, attenuated negative affect, as well as withdrawal and craving. Negative mood increased smoking reinforcement. However, neither actual nor expected nicotine dose had much influence on these responses; even those smokers receiving and expecting a denic cigarette reported attenuated negative affect. A follow-up comparison suggested that the sensory effects of smoke inhalation, but not the simple motor effects of smoking behavior, were responsible. Thus, sensory effects of smoke inhalation had a greater influence on relieving negative affect than actual or expected nicotine intake.     

Cognitive-behavioral therapy for insomnia in alcohol dependent patients: a randomized controlled pilot trial

In a randomized controlled trial, we evaluated the efficacy of cognitive-behavioral treatment for insomnia to improve sleep and daytime symptoms, and to reduce relapse in recovering alcohol dependent (AD) participants. Seventeen abstinent AD patients with insomnia (6 women, mean age 46.2 ± 10.1 years) were randomized to 8 sessions of cognitive-behavioral treatment for insomnia for AD (CBTI-AD, n = 9) or to a behavioral placebo treatment (BPT, n = 8). Subjective measures of sleep, daytime consequences of insomnia and AD, alcohol use, and treatment fidelity were collected at baseline and post-treatment. Diary-rated sleep efficiency and wake after sleep onset, and daytime ratings of General Fatigue on the Multidimensional Fatigue Inventory improved more in the CBTI-AD compared to the BPT group. In addition, more subjects were classified as treatment responders following CBTI-AD. No group differences were found in the number of participants who relapsed to any drinking or who relapsed to heavy drinking. The findings suggest that cognitive-behavioral insomnia therapy benefits subjective sleep and daytime symptoms in recovering AD participants with insomnia more than placebo. The benefits of treating insomnia on drinking outcomes are less apparent.     

Effects of pyridoxine on dreaming: a preliminary study

The effect of pyridoxine (Vitamin B-6) on dreaming was investigated in a placebo, double-blind study to examine various claims that Vitamin B-6 increases dream vividness or the ability to recall dreams. 12 college students participated in all three treatment conditions, each of which involved ingesting either 100 mg B-6, 250 mg B-6, or a placebo prior to bedtime for a period of five consecutive days. The treatment conditions were completely counterbalanced and a two-day wash-out period occurred between the three five-day treatment blocks. Morning self-reports indicated a significant difference in dream-salience scores (this is a composite score containing measures on vividness, bizarreness, emotionality, and color) between the 250-mg condition and placebo over the first three days of each treatment. The data for dream salience suggests that Vitamin B-6 may act by increasing cortical arousal during periods of rapid eve movement (REM) sleep. An hypothesis is presented involving the role of B-6 in the conversion of tryptophan to serotonin. However, this first study needs to be replicated using the same procedures and also demonstrated in a sleep laboratory before the results can be considered certain.     

Motivation and expectancy influences in placebo responding: The mediating role of attention

Drawing upon research in perception and motivation, the current study proposes a motivation‐attention model of placebo in which more motivated persons pay greater attention to placebo‐related stimuli, directly influencing placebo response. We manipulated both motivation to respond to placebo and expectations of placebo response in a 2 × 2 design. Participants (N = 152) evaluated a series of placebo pheromones (slightly scented water) of potential romantic dates and made desirability ratings. Consistent with hypotheses, more highly motivated participants demonstrated greater placebo responses, as evidenced by higher desirability ratings of the “pheromone” and greater variability among ratings, when compared to less motivated participants. Moreover, the relation between motivation and placebo response was mediated by attention. Contrary to expectations, we found no effect for expectancy. These findings highlight the importance of motivation and the mediating factor of attention in placebo and support goal‐oriented models of placebo.     

Dreaming and waking: similarities and differences revisited

Dreaming is often characterized as lacking high-order cognitive (HOC) skills. In two studies, we test the alternative hypothesis that the dreaming mind is highly similar to the waking mind. Multiple experience samples were obtained from late-night REM sleep and waking, following a systematic protocol described in Kahan (2001). Results indicated that reported dreaming and waking experiences are surprisingly similar in their cognitive and sensory qualities. Concurrently, ratings of dreaming and waking experiences were markedly different on questions of general reality orientation and logical organization (e.g., the bizarreness or typicality of the events, actions, and locations). Consistent with other recent studies (e.g., [Bulkeley and Kahan, 2008] and [Kozmová and Wolman, 2006] ), experiences sampled from dreaming and waking were more similar with respect to their process features than with respect to their structural features.     

Relative efficacy of methylphenidate and behavior modification in hyperkinetic children: An interim report

Children reported to be hyperactive in school and with behavior difficulties at home were randomly assigned to methylphenidate, behavior therapy and placebo, or behavior therapy with methylphenidate for an 8-week period. Rating scales were obtained from teachers and parents. Independent blind observers rated childrens' classroom behavior on a weekly basis. A behavior therapy program was implemented in the home and at school. Methylphenidate dosage was individualized. Ratings of behavior deviance were significantly reduced by all treatments. However, a significant advantage for the groups receiving methylphenidate was found over the group receiving behavior therapy and placebo. No significant differences between methylphenidate alone and methylphenidate combined with behavior therapy were obtained. Global ratings of improvement done by teachers favored the combined treatment of behavior therapy and methylphenidate over behavior therapy and placebo. No differences among treatments were found in the mothers' global ratings of improvement. The results indicate that though all three treatments were effective, methylphenidate was significantly superior to behavior therapy alone.This study was supported in part by grant MH 18579, and by grant No. 3-621 from the Long Island Jewish-Hillside Medical Center. The authors wish to thank the behavior therapists, Drs. Jeffrey Felixbrod and Marion Pheterson, as well as Ms. Patricia Ramsey, who was responsible for data analysis.     

Investigator ratings of ADHD symptoms during a randomized, placebo-controlled trial of atomoxetine: a comparison of parents and teachers as informants

This study compared investigator ratings of ADHD symptoms based on interviews with parents and teachers during a doubleblind, placebo-controlled study of atomoxetine. Investigators completed the ADHD Rating Scale: Investigator (ADHDRS-I) based on separate semistructured interviews with the primary caretaker and teacher of the participant. Interviews were conducted at Visits 2 to 7 during a double-blind treatment protocol comparing atomoxetine (N= 10) and placebo (N= 6). Both parent and teacher-based ratings were sensitive to change in ADHD symptoms with atomoxetine treatment. Parent-based assessment differentiated significantly between treatment with atomoxetine and placebo, whereas teacher-based assessment was less sensitive to change. Parents and teachers showed good agreement on change in ADHDRS-I scores. Investigator ratings based on parent- and teacher-report were sensitive to change in symptoms of ADHD during treatment with atomoxetine. Despite good agreement between parent- and teacher-based ratings of symptom change, parent-based ADHD symptom ratings are more sensitive to symptom change.     

Psychoactive drug effects in a hyperactive child: A case study analysis of behavior change and teacher attention

The effects of methylphenidate on the behavior and teacher interactions of a 9-year-old hyperactive female were analyzed. Observations of the subject's task-related and disruptive behaviors and of interactions between the subject and her classroom teacher were made when the subject received the active drug and an inert placebo. Teacher's ratings of the subject's classroom behavior and measures of her academic performance were also obtained. Results showed that when the subject was receiving methylphenidate she engaged in task-related activities a greater percent of the time, had a higher percent of teacher interactions that were instructional in quality, and received lower behavior ratings by the teacher than when she was receiving a placebo. The results suggest that the use of medication may enable the hyperactive child to profit both behaviorally and academically.     

HUMOR AND INCLINATION TO LAUGH: EMOTIONAL REACTIONS TO STIMULI OF DIFFERENT DIVERGENCE FROM A RANGE OF EXPECTANCY

An experiment was conducted to test the general hypothesis, derived from the incongruity theory of humor, that the experience of humor or of the inclination to laugh is a function of the divergence of a perceived state of affairs from the expected state. The hypothesis was tested with weights as stimuli in two designs. In the first the range of expectancy was defined in terms of the proportion of "heavy" ratings in the subject group at various initial weights. In the second the range of expectancy among subjects was assumed to move with experience with various ranges of weights. The results of both designs supported the hypothesis.     

Outcomes From the Transdiagnostic Sleep and Circadian Intervention (TranS-C) for Midlife and Older Adults With Serious Mental Illness and Sleep and Circadian Dysfunction

The present study tested outcomes of the Transdiagnostic Sleep and Circadian Intervention (TranS-C) among midlife and older adults with serious mental illness (SMI). Further, we tested predictors—credibility, expectancy, usefulness, and utilization—that may affect TranS-C outcomes. Midlife and older participants from a community setting (>49 years, 62.3% female, 37.7% African American or Black) with sleep and circadian problems and SMI were randomized to receive TranS-C plus usual care (TranS-C+UC, n = 27) or usual care followed by delayed treatment with TranS-C (UC-DT, n = 26). Immediate and delayed TranS-C data were combined to increase power (combined n = 52). Outcomes were assessed at pretreatment, posttreatment, and 6-month follow-up. Credibility and expectancy were assessed during the second session. Usefulness and utilization of TranS-C skills were assessed at posttreatment and 6-month follow-up. TranS-C+UC, relative to UC-DT, was associated with improvements in depression symptoms, sleep disturbance, overall sleep health, and select sleep/wake outcomes, though not all improvements were sustained at 6-month follow-up. Lower usefulness of TranS-C skills predicted more severe sleep disturbance at posttreatment and daytime sleep-related impairment at posttreatment and 6-month follow-up. Lower utilization predicted more severe psychiatric symptoms at posttreatment, sleep disturbance at posttreatment and 6-month follow-up, and overall impairment and daytime sleep-related impairment at 6-month follow-up. Higher credibility and expectancy predicted greater usefulness of TranS-C skills at posttreatment and 6-month follow-up and greater utilization at 6-month follow-up. Together, findings highlight benefits of TranS-C for midlife and older adults with SMI. However, boosting credibility, expectancy, utilization, and usefulness may meaningfully improve TranS-C outcomes.     

Melatonin rhythm abnormalities and sleep disorders in the elderly

Biological aging is often associated with sleep problems and daytime napping. Complaints of difficulty in initiating and maintaining sleep, as well as daytime drowsiness, are more common in the elderly than in any other age group. This report reviews evidence that impaired melatonin secretion is associated with sleep disorders in old age. Circulating melatonin levels have been found to be significantly lower and onset and peak times have been delayed in elderly insomniacs as compared to age-matched control subjects. In view of these findings, we investigated the effects of melatonin treatment on melatonin-deficient insomnia in the elderly. From the results of our study, it seems likely that melatonin replacement therapy may be beneficial in the initiation and maintenance of sleep in this population.     

Reinforcing effects of caffeine in coffee and capsules.

In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference for caffeine was demonstrated whether or not preference testing was preceded by a period of 10 to 37 days of caffeine abstinence, suggesting that a recent history of heavy caffeine intake (tolerance/dependence) was not a necessary condition for caffeine to function as a reinforcer. In Experiment 2, 6 subjects had 10 opportunities each day to self-administer a cup of coffee or (on different days) a capsule, dependent upon completing a work requirement that progressively increased and then decreased over days. Each day, one of four conditions was studied: caffeinated coffee (100 mg/cup), decaffeinated coffee, caffeine capsules (100 mg/capsule), or placebo capsules. Caffeinated coffee maintained the most self-administration, significantly higher than decaffeinated coffee and placebo capsules but not different from caffeine capsules. Both decaffeinated coffee and caffeine capsules were significantly higher than placebo capsules but not different from each other. In both experiments, subject ratings of "linking" of coffee or capsules covaried with the self-administration measures. These experiments provide the clearest demonstrations to date of the reinforcing effects of caffeine in capsules and in coffee.     

Anticipatory attention during the sleep onset period

To examine whether anticipatory attention or expectancy is a cognitive process that is automatic or requires conscious control, we employed a paired-stimulus event-related potential (ERP) paradigm during the transition to sleep. The slow negative ERP wave observed between two successive stimuli, the Contingent Negative Variation (CNV), reflects attention and expectancy to the second stimulus. Thirteen good sleepers were instructed to respond to the second stimulus in a pair during waking sessions. In a non-response paradigm modified for sleep, participants then fell asleep while tones played. As expected, N1 decreased and P2 increased in amplitude systematically with the loss of consciousness at sleep onset; the CNV was increasingly more positive. Sleep onset latency was correlated with the amplitude of the CNV. The systematic attenuation of the CNV waveform at sleep onset and its absence in sleep indicates that anticipatory attention requires endogenous conscious control.     

Epidemiologic study of sleep disorders in Kuwaiti adolescents.

A sample of 2,574 volunteer Kuwaiti boys (n = 1,309) and girls (n = 1,265) in secondary schools were recruited. Their ages ranged from 14 to 18 years. 13 items were used to assess prevalence of insomnia, hypersomnia, nightmares, sleepwalking, sleep terror, and narcolepsy. Participants were requested to respond according to the past month on a 5-point scale. The summation of responses in the last two options, i.e., "Much" and "Very much" was considered as the point prevalence rates. Girls had significantly higher mean ratings than boys on the following items: difficulty initiating sleep, fitful and disturbed sleep, waking up several times, nightmares, and sleep terror, while boys had significantly higher mean ratings on sleepwalking and "watching TV causes naps or sleep." The point prevalence on all the items for boys ranged from 4.6% to 35.2%, and that for girls ranged between 1.0% and 37.5%. One should keep in mind that the present sample was not a clinical one.     

Sleep normalization and decrease in dissociative experiences: evaluation in an inpatient sample

We conducted a longitudinal study to investigate the relation between sleep experiences and dissociative symptoms in a mixed inpatient sample at a private clinic evaluated on arrival and at discharge 6 to 8 weeks later. Using hierarchical regression analyses and structural equation modeling, we found a link between sleep experiences and dissociative symptoms and determined that specifically decreases in narcoleptic experiences rather than insomnia accompany a reduction in dissociative symptoms. Although sleep improvements were associated with a general reduction in psychopathology, this reduction could not fully account for the substantial and specific effect that we found for dissociation. Our findings are consistent with Watson's (2001) hypothesis that disruptions in the sleep-wake cycle lead to intrusions of sleep phenomena into waking consciousness, resulting in dissociative experiences. Accordingly, sleep hygiene may contribute to the treatment or prevention of dissociative symptoms.     

Three consecutive nights of sleep loss: Effects of morning caffeine consumption on subjective sleepiness/alertness,reaction time and simulated driving performance

Caffeinated products are often consumed as a popular countermeasure to the effects of sleep loss. However, the efficacy of caffeine to exert these effects after consecutive nights of sleep loss is poorly understood. The aim of this study was to investigate the effects of three consecutive nights of restricted sleep and morning caffeine consumption on subjective ratings of sleepiness/alertness, reaction time, and simulated driving performance. Twenty healthy, habitual caffeine consumers (11 females; age: 23.3 ± 5.7 y; BMI: 22.3 ± 3.5 kg⋅m⁻²; caffeine intake: 204 ± 89 mg⋅day⁻¹; Mean ± SD) who had normal sleeping patterns (≥8 h⋅night⁻¹) participated in this double-blind, placebo-controlled, randomised study. Following one night of normal sleep (≥8 h time in bed (TIB)), participants underwent three consecutive nights of restricted sleep (5 h TIB). Participants received caffeine (200 mg; n = 10) or placebo (n = 10) capsules each morning and all participants received caffeine (100 mg) capsules each afternoon. Subjective ratings of alertness, concentration and tiredness were measured before and 1 h after morning capsule administration. Choice Reaction Time (CRT) was examined 1 h after morning capsule administration, with response speed and accuracy as outcome variables. Driving performance was assessed using a 30 min simulated driving task, with lateral (standard deviation of lane position [SDLP]; total number of line crossings [LC]) and longitudinal (standard deviation of speed [SDSP]) measures of vehicle control as outcome variables. Alertness and concentration significantly decreased, and tiredness increased across the three days of sleep loss. Caffeine only marginally alleviated these effects. No differences were observed between treatments or across trial days for response speed and accuracy on the CRT task. Likewise, no significant differences were observed between groups or across trial days for any measures of simulated driving performance. Overall, results from this study indicate that three consecutive days of sleep loss influence subjective ratings of alertness, concentration and tiredness, but does not alter CRT or simulated driving performance. Caffeine may alleviate some of the negative subjective effects imposed by restricted sleep, but the efficacy of caffeine to attenuate performance changes in CRT and driving performance were unable to be observed.     

Hormonal and behavioural abnormalities induced by stress in utero: an animal model for depression

Prenatal stress in rats can exert profound influence on the off spring's development, inducing abnormalities such as increased "anxiety", "emotionality" or "depression-like" behaviours.Prenatal stress has long-term effects on the development of the hypothalamo-pituitary-adrenal(HPA) axis and forebrain cholinergic systems. These long-term neuroendocrinological effects are mediated, at least in part, by stress-induced maternal corticosterone increase during pregnancy and stress-induced maternal anxiety during the postnatal period. We have shown a significant phase advance in the circadian rhythms of corticosterone secretion and locomotor activity in prenatally-stressed (PNS) rats. When subjected to an abrupt shift in the light-dark(LD) cycle, PNS rats resynchronized their activity rhythm more slowly than control rats. In view of the data suggesting abnormalities in the circadian timing system in these animals, we have investigated the effects of prenatal stress on the sleep-wake cycle in adult male rats. PNS rats exhibited various changes in sleep-wake parameters, including a dramatic increase in the amount of paradoxical sleep. Taken together, our results indicate that prenatal stress can induce increased responses to stress and abnormal circadian rhythms and sleep in adult rats.Various clinical observations in humans suggest a possible pathophysiological link between depression and disturbances in circadian rhythmicity. Circadian abnormalities in depression can be related to those found in PNS rats. Interestingly, we have recently shown that the increased immobility in the forced swimming test observed in PNS rats can be corrected by chronic treatment with the antidepressant tianeptine, or with melatonin or S23478, a melatonin agonist. Those results reinforce the idea of the usefulness of PNS rats as an appropriate animal model to study human depression and support a new antidepressant-like effect of melatonin and the melatonin agonist S23478.     

Sleep Loss and Temporal Memory

Historical evidence suggests that sleep deprivation affects temporal memory, but this has not been studied systematically. We explored the effects of 36 hr of sleep deprivation on a neuropsychological test of temporal memory. To promote optimal performance, the test was short, novel, and interesting, and caffeine was used to reduce 'sleepiness'. A total of 40 young adults were randomized into four groups: control + caffeine (Cc), control + placebo (Cp), sleep deprived + caffeine (SDc), and sleep deprived + placebo (SDp). Controls slept normally. Caffeine (350 mg) or placebo were given just prior to testing. The task comprised colour photographs of unknown faces and had two components: recognition memory (distinction between previously presented and novel faces), and recency discrimination (temporal memory), when a previously shown face was presented. An interpolated task, self-ordered pointing, acted as a distraction. Caffeine had no effects within control conditions, but significantly reduced subjective sleepiness in SDc. Recognition was unaffected by sleep deprivation, whereas for recency, sleep deprivation groups scored significantly lower than controls. There was no significant improvement of recency with caffeine in the SDc group. Both sleep deprivation groups had poorer insight into their performance with recency. Self-ordered pointing remained unchanged. In conclusion, sleep deprivation impairs temporal memory (i.e. recency) despite other conditions promoting optimal performance.