Is there a common motor dysregulation in sleepwalking and REM sleep behaviour disorder?

This study sought to determine if there is any overlap between the two major non‐rapid eye movement and rapid eye movement parasomnias, i.e. sleepwalking/sleep terrors and rapid eye movement sleep behaviour disorder. We assessed adult patients with sleepwalking/sleep terrors using rapid eye movement sleep behaviour disorder screening questionnaires and determined if they had enhanced muscle tone during rapid eye movement sleep. Conversely, we assessed rapid eye movement sleep behaviour disorder patients using the Paris Arousal Disorders Severity Scale and determined if they had more N3 awakenings. The 251 participants included 64 patients with rapid eye movement sleep behaviour disorder (29 with idiopathic rapid eye movement sleep behaviour disorder and 35 with rapid eye movement sleep behaviour disorder associated with Parkinson's disease), 62 patients with sleepwalking/sleep terrors, 66 old healthy controls (age‐matched with the rapid eye movement sleep behaviour disorder group) and 59 young healthy controls (age‐matched with the sleepwalking/sleep terrors group). They completed the rapid eye movement sleep behaviour disorder screening questionnaire, rapid eye movement sleep behaviour disorder single question and Paris Arousal Disorders Severity Scale. In addition, all the participants underwent a video‐polysomnography. The sleepwalking/sleep terrors patients scored positive on rapid eye movement sleep behaviour disorder scales and had a higher percentage of ‘any’ phasic rapid eye movement sleep without atonia when compared with controls; however, these patients did not have higher tonic rapid eye movement sleep without atonia or complex behaviours during rapid eye movement sleep. Patients with rapid eye movement sleep behaviour disorder had moderately elevated scores on the Paris Arousal Disorders Severity Scale but did not exhibit more N3 arousals (suggestive of non‐rapid eye movement parasomnia) than the control group. These results indicate that dream‐enacting behaviours (assessed by rapid eye movement sleep behaviour disorder screening questionnaires) are commonly reported by sleepwalking/sleep terrors patients, thus decreasing the questionnaire's specificity. Furthermore, sleepwalking/sleep terrors patients have excessive twitching during rapid eye movement sleep, which may result either from a higher dreaming activity in rapid eye movement sleep or from a more generalised non‐rapid eye movement/rapid eye movement motor dyscontrol during sleep.     

Sleep onset rapid-eye-movement episodes in narcolepsy: REM sleep pressure or nonREM-REM sleep dysregulation?

SUMMARY  Thirty-two narcoleptic subjects with excessive daytime sleepiness and cataplexy were recorded for 33 continuous hours. The continuous polysomnographic recording (CPSG) was followed by a standard MSLT at 2-h intervals. There were 64 sleep onset REM episodes (SOREMs) vs 64 sleep onset nonREM episodes (SONREMs) during the CPSG, and 102 SOREMs vs 50 SONREMS during the MSLT. Both sleep onset types peaked at 13–15 h during the CPSG while sleep onsets were evenly distributed during the MSLT. In the latter procedure, the mean sleep latency was significantly shorter with SOREMs occurrence than with SONREMs occurrence. Two factors were extracted in each procedure by means of a Varimax Rotated Factor Analysis. During the CPSG, SOREMs were related to the preceding nocturnal sleep parameters in the first factor, and to the daytime total sleep time and the total number of sleep onsets in the second factor. During the MSLT, SOREMs were related only to the mean sleep latency and the total number of sleep onsets. It was concluded that the occurrence of SOREMs is primarily due to the residual somnolence in narcoleptic subjects. However, their occurrence during the MSLT is largely independent of the prior history of sleep and waking. Thus, we propose a nonREM-REM sleep dysregulation hypothesis to account for the appearance of SOREMs in narcolepsy.     

Motor dyscontrol in sleep of narcoleptic patients (a lifelong development?)

In our retrospective study 27 narcoleptic patients were divided into two groups: Group A comprised 14 patients (10 male, 4 female) with a history of REM behaviour disorder (RBD) and Group B comprised 13 age- and sex-matched patients (10 male, 3 female) without a history of RBD. Polygraphic and videometry data, medical history, medication, blood chemistry, psychological and neuroradiological data of the two groups of patients were compared. The narcoleptic patients with a history of RBD differed from the narcoleptic control group without history of RBD in that they had: (a) a higher frequency of parasomnias in their history; (b) a higher percentage of stage 1 REM (P < 0.01); (c) a lower number of arousals during REM sleep; (d) fewer sleep stage changes. Compared to the heterogenous RBD patient group of Mahowald and Schenck, the REM behaviour of most of our narcoleptic patients was less violent. Thus it can be speculated that the motor disorder in REM sleep might still be in the process of developing towards a full-blown REM sleep behaviour disorder. In a possible lifelong development of a motor disorder starting in NREM sleep, the onset of narcolepsy might represent the turning point for its intrusion into REM sleep.     

Is the nonREM-REM sleep cycle reset by forced awakenings from REM sleep?

In selective REM sleep deprivation (SRSD), the occurrence of stage REM is repeatedly interrupted by short awakenings. Typically, the interventions aggregate in clusters resembling the REM episodes in undisturbed sleep. This salient phenomenon can easily be explained if the nonREM-REM sleep process is continued during the periods of forced wakefulness. However, earlier studies have alternatively suggested that awakenings from sleep might rather discontinue and reset the ultradian process. Theoretically, the two explanations predict a different distribution of REM episode duration.We evaluated 117 SRSD treatment nights recorded from 14 depressive inpatients receiving low dosages of Trimipramine. The alarms were triggered by an automatic mechanism for the detection of REM sleep and had to be canceled by the subjects themselves. The REM episodes were determined as in undisturbed sleep-they had to include the remaining REM activity and were separated by 30 min without REM epochs. The frequency histogram of REM episodes declined exponentially with episode duration for each of the first four sleep cycles. The duration of nonREM intervals revealed bimodal distributions. These results were found consistent with the model assuming a reset of the ultradian cycle upon awakening. Whether REM or nonREM activity is resumed on return to sleep can be modeled by a random decision whereby the probability for REM sleep might depend on the momentary REM pressure.     

Why REM sleep? Clues beyond the laboratory in a more challenging world

REM sleep (REM) seems more likely to prepare for ensuing wakefulness rather than provides recovery from prior wakefulness, as happens with ‘deeper’ nonREM. Many of REM's characteristics are ‘wake-like’ (unlike nonREM), including several common to feeding. These, with recent findings outside sleep, provide perspectives on REM beyond those from the laboratory. REM can interchange with a wakefulness involving motor output, indicating that REM's atonia is integral to its function. Wakefulness for ‘wild’ mammals largely comprises exploration; a complex opportunistic behaviour mostly for foraging, involving: curiosity, minimising risks, (emotional) coping, navigation, when (including circadian timing) to investigate new destinations; all linked to ‘purposeful, goal directed movement’. REM reflects these adaptive behaviours (including epigenesis), masked in laboratories having constrained, safe, unchanging, unchallenging, featureless, exploration-free environments with ad lib food. Similarly masked may be REM's functions for today's humans living safe, routine lives, with easy food accessibility. In these respects animal and human REM studies are not sufficiently ‘ecological’.     

Is there a specific polysomnographic sleep pattern in children with attention deficit/hyperactivity disorder?

The aim of the study was to characterize the sleep pattern in children with attention deficit/hyperactivity disorder (ADHD). By means of polysomnography (PSG), sleep patterns were studied in 17 unmedicated preadolescent boys rigorously diagnosed with ADHD and 17 control boys precisely matched for age and intelligence. Although ADHD children did not display a general sleep alteration, major PSG data showed a significant increase in the duration of the absolute rapid eye movement (REM) sleep and the number of sleep cycles in ADHD group when compared with controls. In addition, REM sleep latency tended to be shorter in ADHD children. These results suggest that in ADHD children, a forced REM sleep initiation may produce a higher incidence of sleep cycles and may also contribute to an increased duration of the absolute REM sleep. The overall pattern of the findings implies that a forced ultradian cycling appears characteristic for the sleep in ADHD children, which may be related to alterations of brain monoamines and cortical inhibitory control accompanying the ADHD psychopathology.     

Single and Sequential REM sleep episodes in humans: a phylogenetic left-over?

The occurrence of REM sleep in the rat appears to be under the control of either sleep related processes and homeostatic regulation of physiological variables. With respect to this, it has been observed that in this species REM sleep may occur in the form of two types of episodes, Single and Sequential episodes, which are supposed to play a different functional role. Since it is possible to distinguish Single and Sequential REM sleep episodes also in human beings, the aim of this pilot study was to asses whether a sleep deprivation may differently affect these two types of REM episodes. The sleep deprivation was induced in young human subjects by a progressive restriction of sleep within the same night period. Seventy-two PSG tracing belonging to six subjects have been analyzed. The results show that sleep deprivation does not significantly affect the relative occurrence of Single and Sequential REM sleep episodes, suggesting that in human beings these two types of REM episodes might not have a different functional role.     

Is voluntary abortion a seasonal disorder of mood?

BACKGROUND: Depressive mood and suicides are more frequent in women seeking voluntary abortion and occur in a seasonal rhythmic fashion. Whether voluntary abortion shows a similar seasonal rhythm was investigated in this study. METHODS: A 4-year analysis was performed on the database of the National Institute of Statistics (ISTAT) (508,130 abortions) and on the medical records of our institute (3463 abortions). The ratio of voluntary abortions to the number of vital pregnancies (terminated with birth and voluntary abortion) present at the third month of gestation (8--12 weeks) was evaluated. Analyses were carried out by the periodogram method. RESULTS: The rate of voluntary abortions showed a seasonal rhythm with an amplitude of 6.1--6.7% and peaked in May (+/-38 days). The national frequency of female suicides, obtained from the same ISTAT database, showed a similar rhythm, with an amplitude of 11.1% and maximal rate in June (+/-37 days). CONCLUSIONS: The present data show a seasonal rhythm in the rate of voluntary abortion, which is almost identical to that of female suicides. This link suggests common provocative mechanisms and may indicate common preventative measures.     

Is sepsis a pro-resolution deficiency disorder?

Sepsis is due to a systemic inflammatory response to both infectious and non-infectious disorders; and when it leads to hypotension and organ dysfunction, septic shock occurs. Mortality in sepsis is due to multiple organ dysfunction. The early stages of sepsis are characterized by excessive generation of inflammatory mediators; however, as sepsis develops into chronic severe sepsis, immunosuppression dominates. Despite several advances in our understanding of the pathogenesis of sepsis both its prevention and management remains elusive. It is proposed that sepsis is due to failure of production of appropriate amounts of pro-resolution bioactive lipids such as lipoxins, resolvins, protectins, maresins and nitrolipids that suppress inappropriate inflammation, production of pro-inflammatory cytokines, free radical generation, and leukocyte activation and enhance resolution of inflammation and wound healing.     

Is somnambulism a distinct disorder of humans and not seen in non-human primates?

Though somnambulism (sleepwalking) is a well-recognized sleep disorder in humans, a biomedical literature search in Medline and Primate Literature bibliographic databases showed no publications on sleepwalking in non-human primates. From this finding, two inferences can be made. First is that somnambulism may be present in non-human primates; but due to limitations in expertise and methodological resources as well as narrow focus of research interest, until now researchers have not detected it in wild and/or captive conditions. Second, somnambulism does not exist in non-human primates including apes (chimpanzee, gorilla, orang-utan and gibbon); and thus, it is a unique behavioral disorder present only in humans. It is premature to conclude which of these two inferences is correct. In Jane Goodall's view, sleepwalking behavior is absent in chimpanzees. If further field observations can confirm Goodall's assertion that somnambulism is indeed absent in chimpanzees, it will be of evolutionary and medical interest to know why this parasomnic behavior became established in humans during the past 5.5 million years or so.     

Is ADHD a valid disorder in children with intellectual delays?

To assess the validity of ADHD in children with mental retardation, we applied Robins and Guze's [Robins, E., and Guze, S.B. (1970). Establishment of diagnostic validity in psychiatric illness: Its application to schizophrenia. American Journal of Psychiatry, 126, 983-987.] criteria for determining the validity of a psychiatric disorder. We review the literature describing clinical correlates, family history, treatment response, laboratory studies, course, and outcome of children with ADHD and mental retardation. Although clearly an area in need of further research, there is preliminary evidence to suggest that ADHD is a valid psychiatric condition in children with mental retardation. Nevertheless, without knowing the base rates of ADHD symptoms in the mental retardation population, the positive predictive power and negative predictive power of ADHD symptoms in this population remain an open question. In addition to assessment of base rate symptoms, future research should consider what diagnostic algorithm may best be applied to the diagnosis of ADHD in mental retardation.     

Is premenstrual dysphoria a variant of panic disorder? A review

Patients with premenstrual dysphoric disorder (PMDD) and patients with panic disorder (PD) both experience high rates of panic attacks in laboratory panic provocation studies. Recently, this shared elevated rate of challenge-induced panic has received increasing attention. Researchers have suggested that PMDD and panic disorder may share a pathophysiological or psychobiological link. The purpose of this paper is to review the findings from PMDD challenge studies and the theories advanced to connect PMDD to panic disorder. Taken together, the results of the PMDD challenge studies confirm that agents that incite panic in PD patients do so as well in PMDD women. This shared elevated challenge-induced panic cannot be accounted for by explanations such as a history of PD in PMDD women. None of the physiological theories as currently expressed--suffocation false alarm, gamma-aminobutyric acid (GABA), noradrenergic, serotonergic, and cholecystokinin--yet provides a compelling candidate to account for shared elevated challenge-induced panic in PD and PMDD patients. Psychological perspectives on panic emphasize that bodily sensations themselves can cause fear. Researchers have yet to apply several influential psychological approaches--conditioning, catastrophic misinterpretation, and anxiety sensitivity--to PMDD patients. Because psychological factors influence anxious responding in challenge studies, the search for the biological abnormality best accounting for PMDD panic might benefit from a reframing of the question to one that considers the psychological perspective as well.     

Changes of sleep EEG slow-wave activity in response to sleep manipulations: to what extent are they related to changes in REM sleep latency?

SUMMARY  Sleep interventions may have direct effects on slow-wave activity (SWA, i.e. power of the sleep EEG signal in the 0.75-4.5 Hz range) as well as indirect ones caused by changes in REM sleep (REMS) latency. The effects of changes in REMS latency on SWA were investigated by analysing simulations with a mathematical model. Mean SWA in the first non-REMS episode shows an initial increase and a later decline as a function of REMS latency. In the second non-REMS episode, mean SWA decreases with increasing REMS latency. These results of the simulations were validated with experimental data.
In the evaluation of the effects of sleep interventions on SWA the effects of the timing of REMS have to be accounted for. The analysis of SWA over a sufficiently long constant amount of time spent in non-REMS proves to be relatively independent of REMS latency, which allows conclusions about the effects of sleep interventions on SWA per se.     

Does REM sleep contribute to subjective wake time in primary insomnia? A comparison of polysomnographic and subjective sleep in 100 patients

Primary insomnia (PI) is characterized by low subjective sleep quality which cannot always be verified using polysomnography (PSG). To shed light on this discrepancy, subjective estimates of sleep and PSG variables were compared in patients with PI and good sleeper controls (GSC). 100 patients with PI (age: 42.57 +/- 12.50 years, medication free for at least 14 days) and 100 GSC (41.12 +/- 13.99 years) with a sex distribution of 46 men and 54 women in each group were included. Both PSG and questionnaire variables showed clear impairments of sleep quality in PI compared with GSC. The arousal index within total sleep time was increased, which was mainly because of a strong increase within rapid eye movement (REM) sleep. Subjectively, more PI than GSC subjects estimated wake times longer than obtained from PSG. Linear modeling analysis of subjective wake time in terms of PSG parameters revealed that in addition to PSG defined wake time, REM sleep time contributed significantly to subjective wake time. This REM sleep contribution was larger for PI than for GSC subjects. The findings suggest that REM sleep-related processes might contribute to subjectively disturbed sleep and the perception of waking time in patients with PI.     

Symptoms of depression in late luteal phase dysphoric disorder: a variant of mood disorder?

BACKGROUND: In premenstrual syndrome, depressed mood in the luteal phase of the menstrual cycle is acknowledged, whereas the presence of symptoms of depression during the follicular phase remains in debate. METHODS: On the basis of prospective daily recording of the presence and severity of symptoms for at least two menstrual cycles, 43 women were diagnosed with Late Luteal Phase Dysphoric Disorder (LLPD) according to the criteria of the third edition revision of the Diagnostic and Statistical Manual of Mental Disorders. They were compared to a group of 85 women who showed no evidence of LLPD for two menstrual cycles. Structured psychiatric interviews were administered during the follicular phase. Only those subjects without Axis I disorders were subsequently included in the study. RESULTS: Those women with minor/moderate symptoms of depression had an odds of suffering from LLPD of 1.9 (95% CI=1.5-2.4, p<0.001) in relation to increasing severity of symptoms of depression at the total MADRS scale (1-point increase). The ORs of LLPD in relation to each dimension (1-point increase) of the emotional/affective, cognitive, and neurovegetative symptoms were 1.6 (95% CI=1.2-2.3, p=0.003), 2.8 (95% CI=0.9-8.5, p=0.077) and 3.3 (95% CI=1.9-5.9, p<0.001), respectively. LIMITATIONS: No hormonal changes that may be associated with symptoms of LLPD were determined in this study. CONCLUSIONS: LLPD is likely to represent a variant of a depressive disorder, where premenstrual psychobiological changes seem to exacerbate mild depressive symptoms and signs to which LLPD women are otherwise predisposed. This hypothesis opens new perspectives for prevention and of even treatment for LLPD. Further longitudinal studies with larger populations and evaluation of hormonal changes are needed to confirm these data.