John Trinder

Sick and tired: Does sleep have a vital role in the immune system?

It is a common belief that we are more susceptible to infections when deprived of sleep. Consistent with this, there is increasing evidence that sleep deprivation has detrimental effects on the immune response, indicating that sleep should be considered a vital part of the immune system and that there is a reciprocal relationship between sleep and immunity. This relationship is important because, over recent decades, there has been a documented decrease in the mean duration and quality of sleep in the population. The concept that lack of sleep might be compromising immunity in the population has far-reaching public-health implications for both individuals and society.

Autonomic activity during human sleep as a function of time and sleep stage.

While there is a developing understanding of the influence of sleep on cardiovascular autonomic activity in humans, there remain unresolved issues. In particular, the effect of time within the sleep period, independent of sleep stage, has not been investigated. Further, the influence of sleep on central sympathetic nervous system (SNS) activity is uncertain because results using the major method applicable to humans, the low frequency (LF) component of heart rate variability (HRV), have been contradictory, and because the method itself is open to criticism. Sleep and cardiac activity were measured in 14 young healthy subjects on three nights. Data was analysed in 2‐min epochs. All epochs meeting specified criteria were identified, beginning 2 h before, until 7 h after, sleep onset. Epoch values were allocated to 30‐min bins and during sleep were also classified into stage 2, slow wave sleep (SWS) and rapid eye movement (REM) sleep. The measures of cardiac activity were heart rate (HR), blood pressure (BP), high frequency (HF) and LF components of HRV and pre‐ejection period (PEP). During non‐rapid eye movement (NREM) sleep autonomic balance shifted from sympathetic to parasympathetic dominance, although this appeared to be more because of a shift in parasympathetic nervous system (PNS) activity. Autonomic balance during REM was in general similar to wakefulness. For BP and the HF and LF components the change occurred abruptly at sleep onset and was then constant over time within each stage of sleep, indicating that any change in autonomic balance over the sleep period is a consequence of the changing distribution of sleep stages. Two variables, HR and PEP, did show time effects reflecting a circadian influence over HR and perhaps time asleep affecting PEP. While both the LF component and PEP showed changes consistent with reduced sympathetic tone during sleep, their pattern of change over time differed.

Affective startle modulation in clinical depression: preliminary findings

BACKGROUND Modulation of the startle reflex by affective foreground stimuli was investigated in a group receiving inpatient treatment for major depressive episodes (n = 14) and an age and gender matched nondepressed group (n = 14). METHODS Participants viewed 27 pleasant, neutral, and unpleasant pictures chosen from the International Affective Picture System. Acoustic startle probes were presented during picture viewing, and participants also rated the affective qualities of the pictures. RESULTS While ratings of the pictures were largely similar between the depressed and nondepressed groups, they displayed dissimilar patterns of startle modulation. In the nondepressed group, blinks elicited during unpleasant pictures were significantly larger than during pleasant pictures, whereas the depressed group failed to show this effect. Analyses, which separated the depressed participants into moderate and severe groups based on Beck Depression Inventory scores, revealed that while the moderately depressed group also showed a normal pattern of startle modulation, the severely depressed showed potentiated startles during the pleasant pictures. CONCLUSIONS These preliminary results suggest that severely depressed patients may respond to some pleasant stimuli as if they are aversive, possibly because such stimuli are seen as signals of frustrative nonreward.

Sleep and circadian influences on cardiac autonomic nervous system activity

To assess the separate contributions of the sleep and circadian systems to changes in cardiac autonomic nervous system (ANS) activity, 12 supine subjects participated in two 26-h constant routines, which were counterbalanced and separated by 1 wk. One routine did not permit sleep, whereas the second allowed the subjects to sleep during their normal sleep phase. Parasympathetic nervous system activity was assessed with respiratory sinus arrhythmia as measured from the spectral analysis of cardiac beat-to-beat intervals. Sympathetic nervous system activity was primarily assessed with the preejection period as estimated from impedance cardiography, although the 0.1-Hz peak from the spectral analysis of cardiac beat-to-beat intervals, the amplitude of the T wave in the electrocardiogram, and heart rate were also measured. Respiratory sinus arrhythymia showed a 24-h rhythm independent of sleep, whereas preejection period only showed a 24-h rhythm if sleep occurred. Thus the findings indicate that parasympathetic nervous system activity is mostly influenced by the circadian system, whereas sympathetic nervous system activity is mostly influenced by the sleep system.To assess the separate contributions of the sleep and circadian systems to changes in cardiac autonomic nervous system (ANS) activity, 12 supine subjects participated in two 26-h constant routines, which were counterbalanced and separated by 1 wk. One routine did not permit sleep, whereas the second allowed the subjects to sleep during their normal sleep phase. Parasympathetic nervous system activity was assessed with respiratory sinus arrhythmia as measured from the spectral analysis of cardiac beat-to-beat intervals. Sympathetic nervous system activity was primarily assessed with the preejection period as estimated from impedance cardiography, although the 0.1-Hz peak from the spectral analysis of cardiac beat-to-beat intervals, the amplitude of the T wave in the electrocardiogram, and heart rate were also measured. Respiratory sinus arrhythymia showed a 24-h rhythm independent of sleep, whereas preejection period only showed a 24-h rhythm if sleep occurred. Thus the findings indicate that parasympathetic nervous system activity is mostly influenced by the circadian system, whereas sympathetic nervous system activity is mostly influenced by the sleep system.

The effects of normal aging on sleep spindle and K-complex production

OBJECTIVES Despite a relatively large body of literature describing the characteristics of sleep spindles and K-complexes in young adults, relatively little research has been conducted in older individuals. The general consensus from the few studies that have addressed this issue is that there is a progressive decrease in the number of spindles and K-complexes with age, although there is large intra-individual variation. Whether or not these changes are an inevitable consequence of the aging process can be addressed by studying healthy older adults who provide an example of the effects of age independently from those of disease. METHODS Fourteen young adults (mean age=21.4+/-2.5 years) and 20 older adults (mean age=75.5+/-6.3 years) participated in the study. All subjects were neurologically and medically healthy and were not taking any medications with a known effect on the central nervous system or sleep. For each subject, a number of characteristics were determined including the number, density (SS/min), amplitude and frequency of all spindles as well as the number and density of K-complexes (KC/min). RESULTS Spindle number, density and duration as well as K-complex number and density were all significantly lower in the elderly compared to the young adults. The EEG frequency within the spindles was significantly higher in the elderly, although the absolute difference was less than 0.5 Hz. Multiple regression analysis indicated that spindle duration and K-complex density were able to predict over 90% of the variance in age. CONCLUSIONS The age-related decrease in sleep spindle and K-complex density is consistent with previous reports and may be interpreted as an age-related alteration of thalamocortical regulatory mechanisms.

The effect of sleep onset on upper airway muscle activity in patients with sleep apnoea versus controls

Pharyngeal dilator muscles are important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously shown that during wakefulness, the activity of both the genioglossus (GGEMG) and tensor palatini (TPEMG) is greater in patients with OSA compared with controls. Further, EMG activity decreases at sleep onset, and the decrement is greater in apnoea patients than in healthy controls. In addition, it is known that the prevalence of OSA is greater in middle‐aged compared with younger men. Thus, we had two goals in this study. First we compared upper airway muscle activity between young and middle‐aged healthy men compared with men with OSA. We also explored the mechanisms responsible for the decrement in muscle activity at sleep onset in these groups. We investigated muscle activity, ventilation , and upper airway resistance (UAR) during wakefulness and sleep onset (transition from α to θ EEG activity) in all three groups. Measurements were obtained during basal breathing (BB) and nasal continuous positive airway pressure (CPAP) was applied to reduce negative pressure‐mediated muscle activation). We found that during wakefulness there was a gradation of GGEMG and UAR (younger < older < OSA) and that muscle activity was reduced by the application of nasal CPAP (to a greater degree in the OSA patients). Although CPAP eliminated differences in UAR during wakefulness and sleep, GGEMG remained greater in the OSA patients. During sleep onset, a greater initial fall in GGEMG was seen in the OSA patients followed by subsequent muscle recruitment in the third to fifth breaths following the α to θ transition. On the CPAP night, and GGEMG still fell further in the OSA patients compared with control subjects. CPAP prevented the rise in UAR at sleep onset along with the associated recruitment in GGEMG. Differences in TPEMG among the groups were not significant. These data suggest that the middle‐aged men had upper airway function midway between that of young normal men and the abnormal airway of those with OSA. Furthermore it suggests that the initial sleep onset reduction in upper airway muscle activity is due to loss of a ‘wakefulness’ stimulus, rather than to loss of responsiveness to negative pressure, and that this wakefulness stimulus may be greater in the OSA patient than in healthy controls.

Cognitive and academic functions are impaired in children with all severities of sleep-disordered breathing

STUDY OBJECTIVE The impact of the broad spectrum of SDB severity on cognition in childhood has not been well studied. This study investigated cognitive function in children with varying severities of SDB and control children with no history of SDB. METHODS One hundred thirty-seven children (75 M) aged 7-12 were studied. Overnight polysomnography (PSG) classified children into four groups: primary snoring (PS) (n = 59), mild obstructive sleep apnea syndrome (OSAS) (n = 24), moderate/severe OSAS (n = 19), and controls (n = 35). Cognition was measured with a short battery of psychological tests including the Wechsler Abbreviated Scale of Intelligence (WASI), the Wide Range Achievement Test-3rd Edition (WRAT-3), the Rey Complex Figure Test (RCFT) and the Controlled Oral Word Association Test (COWAT). RESULTS There was lower general intellectual ability in all children with SDB regardless of severity. Higher rates of impairment were also noted on measures of executive and academic functioning in children with SDB. CONCLUSIONS Our findings suggest that neurocognitive deficits are common in children with SDB regardless of disease severity, highlighting that such difficulties may be present in children in the community who snore but are otherwise healthy; thus our results have important implications for the treatment of pediatric SDB.

Detecting insomnia: comparison of four self‐report measures of sleep in a young adult population

The sensitivity and specificity of four self‐report measures of disordered sleep – the Sleep Impairment Index (SII), the Sleep Disorders Questionnaire (SDQ), the Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS) and the Sleep–Wake Activity Inventory (SWAI) – were compared in subjects with insomnia and normal sleep. Nineteen young adult subjects met DSM‐IV criteria for primary insomnia and another 19 were normal control subjects. Discriminatory characteristics of each measure were assessed using receiver operator characteristic curve analyses. Discriminatory power was maximised for each measure to produce cut‐scores applicable for identification of individuals with insomnia. The DBAS, SII and SDQ psychiatric DIMS subscale were found to correlate, and discriminated well between the two groups. The SWAI nocturnal sleep subscale was not found to be an accurate discriminator. The results suggest differences in the measures in their ability to detect insomnia, and offer guidelines as to the optimal use of test scores to identify young adults suspected of insomnia.

Elevated Blood Pressure During Sleep and Wake in Children With Sleep-Disordered Breathing

OBJECTIVE: Sleep-disordered breathing (SDB) in adults has been associated with elevated blood pressure (BP); however, the effects of severity of SDB on BP in children are uncertain. We addressed this issue by measuring BP noninvasively and continuously during sleep in children with a range of severities of SDB and in a group of nonsnoring control children. METHODS: A total of 105 children referred for assessment of SDB and 36 nonsnoring controls were studied. Routine polysomnography (PSG) was performed with continuous BP monitoring. Children were assigned to groups according to obstructive apnea/hypopnea index (OAHI). BP data were categorized as quiet awake (recorded before sleep onset), non–rapid eye movement sleep 1 and 2 combined, slow-wave sleep, and rapid eye movement sleep. RESULTS: BP during awake before sleep onset and during overnight sleep was elevated by 10 to 15 mm Hg in the 3 SDB groups compared with the control group; this finding was independent of SDB severity. BP during stable sleep (with respiratory events and movements excluded) was also elevated in the children with OSA compared with the control group. BP was elevated in rapid eye movement sleep compared with the non–rapid eye movement sleep, and heart rate was higher during wake state than in all sleep states. CONCLUSIONS: We recorded BP continuously overnight and found that SDB, regardless of the severity, was associated with increased BP during sleep and wake compared with nonsnoring control children. These findings highlight the importance of considering the cardiovascular effects of SDB of any severity in children, and the need to review current clinical management that focuses primarily on more severe SDB.

Nature's clocks and human mood: the circadian system modulates reward motivation

Existing literature on reward motivation pays scant attention to the fact that reward potential of the environment varies dramatically with the light/dark cycle. Evolution, by contrast, treats this fact very seriously: In all species, the circadian system is adapted to optimize the daily rhythm of environmental engagement. We used 3 standard protocols to demonstrate that human reward motivation, as measured in the dynamics of positive affect (PA), is modulated endogenously by the circadian clock. Under naturalistic conditions, 13.0% of PA variance was explained by a 24-hr sinusoid. In a constant routine protocol, 25.0% of PA variance was explained by the unmasked circadian rhythm in core body temperature (CBT). A forced desynchrony study showed PA to align with CBT in exhibiting circadian periodicity independent of a 28-hr sleep/wake cycle. It is concluded that the circadian system modulates reward activation, and implications for models of normal and abnormal mood are discussed.