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1.  Marital quality and the marital bed: Examining the covariation between relationship quality and sleep 
Sleep medicine reviews  2007;11(5):389-404.
The majority of adults sleep with a partner, and for a significant proportion of couples, sleep problems and relationship problems co-occur, yet there has been little systematic study of the association between close relationships and sleep. The association between sleep and relationships is likely to be bi-directional and reciprocal—the quality of close relationships influences sleep and sleep disturbances or sleep disorders influence close relationship quality. Therefore, the purpose of the present review is to summarize the extant research on 1) the impact of co-sleeping on bed partner's sleep; 2) the impact of sleep disturbance or sleep disorders on relationship functioning; and 3) the impact of close personal relationship quality on sleep. In addition, we provide a conceptual model of biopsychosocial pathways to account for the covariation between relationship functioning and sleep. Recognizing the dyadic nature of sleep and incorporating such knowledge into both clinical practice and research in sleep medicine may elucidate key mechanisms in the etiology and maintenance of both sleep disorders and relationship problems and may ultimately inform novel treatments.
PMCID: PMC2644899  PMID: 17854738
Marital quality; close relationships; sleep; sleep disorders
2.  Sleep Disorders in the Older Adult – A Mini-Review 
Gerontology  2009;56(2):181-189.
Approximately 50% of older adults complain of difficulty sleeping. Poor sleep results in increased risk of significant morbidity and mortality. The decrements seen in the sleep of the older adult are often due to a decrease in the ability to get needed sleep. However, the decreased ability is less a function of age and more a function of other factors that accompany aging, such as medical and psychiatric illness, increased medication use, advances in the endogenous circadian clock and a higher prevalence of specific sleep disorders. Given the large number of older adults with sleep complaints and sleep disorders, there is a need for health care professionals to have an increased awareness of these sleep disturbances to better enable them to assess and treat these patients. A thorough sleep history (preferably in the presence of their bed partner) is required for a proper diagnosis, and when appropriate, an overnight sleep recording should be done. Treatment of primary sleep problems can improve the quality of life and daytime functioning of older adults. This paper reviews the diagnoses and characteristics of sleep disorders generally found in the older adult. While aimed at the practicing geriatrician, this paper is also of importance for any gerontologist interested in sleep.
PMCID: PMC2842167  PMID: 19738366
Sleep disorders; Circadian rhythms; Insomnia
3.  Effects of exercise and diet interventions on obesity-related sleep disorders in men: study protocol for a randomized controlled trial 
Trials  2013;14:235.
Sleep is essential for normal and healthy living. Lack of good quality sleep affects physical, mental and emotional functions. Currently, the treatments of obesity-related sleep disorders focus more on suppressing sleep-related symptoms pharmaceutically and are often accompanied by side effects. Thus, there is urgent need for alternative ways to combat chronic sleep disorders. This study will investigate underlying mechanisms of the effects of exercise and diet intervention on obesity-related sleep disorders, the role of gut microbiota in relation to poor quality of sleep and day-time sleepiness, as well as the levels of hormones responsible for sleep-wake cycle regulation.
Participants consist of 330 (target sample) Finnish men aged 30 to 65 years. Among them, we attempt to randomize 180 (target sample) with sleep disorders into exercise and diet intervention. After screening and physician examination, 101 men with sleep disorders are included and are randomly assigned into three groups: exercise (n = 33), diet (n = 35), and control (n = 33). In addition, we attempt to recruit a target number of 150 healthy men without sleep disorders as the reference group. The exercise group undergoes a six-month individualized progressive aerobic exercise program based on initial fitness level. The diet group follows a six month specific individualized diet program. The control group and reference group are asked to maintain their normal activity and diet during intervention. Measurements are taken before and after the intervention. Primary outcomes include objective sleep measurements by polysomnography and a home-based non-contact sleep monitoring system, and subjective sleep evaluation by questionnaires. Secondary outcome measures include anthropometry, body composition, fitness, sleep disorder-related lifestyle risk factors, composition of gut microbiota and adipose tissue metabolism, as well as specific hormone and neurotranmitter levels and inflammatory biomarkers from venous blood samples.
It is expected that the improvement of sleep quality after exercise and diet intervention will be evident both in subjective and objective measures of quality of sleep. Additionally, the change of sleep quality induced by exercise and diet intervention is expected to be related to the changes in specific hormones and inflammatory biomarkers, and in the composition of gut microbiota.
Trial registration
Current Controlled Trials ISRCTN77172005
PMCID: PMC3750567  PMID: 23886347
Lifestyle intervention; Sleep disorders; Quality of sleep; Obstructive sleep apnea; Insomnia; Sleep measurement; Obesity; Gut microbiota; Neurotransmitters
4.  Sleep apnoea syndrome: states of sleep and autonomic dysfunction. 
Eleven patients with upper airway apnoea during sleep (one with SHY-Drager syndrome) were monitored polygraphically for wakefulness, sleep, and cardiovascular variables. Systemic hypertension and most of the severe arrhythmias recorded during sleep were secondary to repetitive obstructive apnonea and were mediated through the autonomic nervous system. Sleep related elevations of pulmonary arterial pressure were not influenced by atropine or impaired autonomic functions. Upper airway sleep apnoea is sleep related; the type of sleep (REM or NREM) is critical in the appearance of abnormalities. The distinction between two patient subgroups (total sleep dependent and NREM sleep dependent) has haemodynamic, and possibly long-term, implications. Sleep apnoea syndrome should be looked for in pateints with the Shy-Drager syndrome.
PMCID: PMC492815  PMID: 199709
5.  Sleep, immunity and inflammation in gastrointestinal disorders 
Sleep disorders have become a global issue, and discovering their causes and consequences are the focus of many research endeavors. An estimated 70 million Americans suffer from some form of sleep disorder. Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability, slower response times and performance detriments. Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health, economic consequences, and most importantly increased all-cause mortality. Several research studies support the associations among sleep, immune function and inflammation. Here, we review the current research linking sleep, immune function, and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders. Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep. The inflammatory cytokines such as tumor necrosis factor, interleukin-1 (IL-1), and IL-6 have been shown to be a significant contributor of sleep disturbances. On the other hand, sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines. Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease, gastro-esophageal reflux, liver disorders and colorectal cancer. In turn, abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases. Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.
PMCID: PMC3882397  PMID: 24409051
Sleep; Immune function; Immunity; Irritable bowel syndrome; Inflammatory bowel disease; Gastro-esophageal reflux disease; Liver disorders; Colon cancer; Circadian rhythm
6.  The effects of deep brain stimulation on sleep in Parkinson’s disease 
Sleep dysfunction is a common nonmotor symptom experienced by patients with Parkinson’s disease (PD). Symptoms, including excessive daytime sleepiness, sleep fragmentation, rapid eye movement (REM) sleep behavior disorder and others, can significantly affect quality of life and daytime functioning in these patients. Recent studies have evaluated the effects of deep brain stimulation (DBS) at various targets on sleep in patients with advanced PD. Several of these studies have provided evidence that subthalamic nucleus DBS improves subjective and objective measures of sleep, including sleep efficiency, nocturnal mobility, and wake after sleep onset (minutes spent awake after initial sleep onset). Although fewer studies have investigated the effects of bilateral internal globus pallidus and thalamic ventral intermedius DBS on sleep, pallidal stimulation does appear to improve subjective sleep quality. Stimulation of the pedunculopontine nucleus has recently been proposed for selected patients with advanced PD to treat severe gait and postural dysfunction. Owing to the role of the pedunculopontine nucleus in modulating behavioral state, the impact of stimulation at this target on sleep has also been evaluated in a small number of patients, showing that pedunculopontine nucleus DBS increases REM sleep. In this review, we discuss the effects of stimulation at these various targets on sleep in patients with PD. Studying the effects of DBS on sleep can enhance our understanding of the pathophysiology of sleep disorders, provide strategies for optimizing clinical benefit from DBS, and may eventually guide novel therapies for sleep dysfunction.
PMCID: PMC3036959  PMID: 21339905
deep brain stimulation; globus pallidus; Parkinson’s disease; pedunculopontine nucleus; sleep; subthalamic nucleus; ventral intermediate nucleus of the thalamus
7.  Effects of transient and persistent cerebrospinal fluid drainage on sleep disordered breathing in patients with idiopathic adult hydrocephalus syndrome 
OBJECTIVES—To examine sleep disordered breathing including obstructive sleep apnoea in patients with idiopathic adult hydrocephalus syndrome (IAHS) and to study the effects of CSF drainage and shunting procedure on sleep disordered breathing.
METHODS—In 17 patients with IAHS polysomnographic investigations were performed before and after lumbar CSF drainage and after shunt operation.
RESULTS—Baseline investigations documented a high prevalence of sleep related obstructive respiratory events (respiratory disturbance index >10 in 65% of the patients) and impaired sleep structure. There was no correlation between respiratory disturbance index and CSF pressure. Minimum oxygen saturation was highly correlated with cognitive function. Neither lumbar CSF drainage nor shunting alleviated the respiratory disturbance index. REM and delta sleep increased initially after shunting but there was no sustained effect on sleep quality.
CONCLUSIONS—Sleep disordered breathing is a prevalent finding in patients with IAHS. The shortcoming of CSF drainage to improve sleep disordered breathing either transiently or permanently implies that sleep disordered breathing is a coexistent condition, or an irreversible consequence of the hydrocephalus, with a potential of causing additional dysfunction in IAHS.

PMCID: PMC2170295  PMID: 9771772
8.  Sleep and its importance in adolescence and in common adolescent somatic and psychiatric conditions 
Restoring sleep is strongly associated with a better physical, cognitive, and psychological well-being. By contrast, poor or disordered sleep is related to impairment of cognitive and psychological functioning and worsened physical health. These associations are well documented not only in adults but also in children and adolescents. Importantly, adolescence is hallmarked by dramatic maturational changes in sleep and its neurobiological regulation, hormonal status, and many psychosocial and physical processes. Thus, the role of sleep in mental and physical health during adolescence and in adolescent patients is complex. However, it has so far received little attention. This review first presents contemporary views about the complex neurobiology of sleep and its functions with important implications for adolescence. Second, existing complex relationships between common adolescent somatic/organic, sleep-related, and psychiatric disorders and certain sleep alterations are discussed. It is concluded that poor or altered sleep in adolescent patients may trigger and maintain many psychiatric and physical disorders or combinations of these conditions, which presumably hinder recovery and may cross into later stages of life. Therefore, timely diagnosis and management of sleep problems appear critical for growth and development in adolescent patients.
PMCID: PMC3119585  PMID: 21731894
cognitive; psychological; neurobiology; growth; development; sleep physiology; rapid eye movement; non-REM sleep; behavioral disorders; adolescents
9.  Genetics of Sleep and Sleep disorders 
Cell  2011;146(2):194-207.
Sleep remains one of the least understood phenomena in biology – even its role in synaptic plasticity remains debatable. Since sleep was recognized to be regulated genetically, intense research has launched on two fronts: the development of model organisms for deciphering the molecular mechanisms of sleep and attempts to identify genetic underpinnings of human sleep disorders. In this Review, we describe how unbiased, high-throughput screens in model organisms are uncovering sleep regulatory mechanisms and how pathways, such as the circadian clock network and specific neurotransmitter signals, have conserved effects on sleep from Drosophila to humans. At the same time, genome-wide association (GWA) studies have uncovered ~14 loci increasing susceptibility to sleep disorders, such as narcolepsy and restless leg syndrome. To conclude, we discuss how these different strategies will be critical to unambiguously defining the function of sleep.
PMCID: PMC3153991  PMID: 21784243
10.  Neurocognitive Consequences of Sleep Deprivation 
Seminars in neurology  2009;29(4):320-339.
Sleep deprivation is associated with considerable social, financial, and health-related costs, in large measure because it produces impaired cognitive performance due to increasing sleep propensity and instability of waking neurobehavioral functions. Cognitive functions particularly affected by sleep loss include psychomotor and cognitive speed, vigilant and executive attention, working memory, and higher cognitive abilities. Chronic sleep-restriction experiments—which model the kind of sleep loss experienced by many individuals with sleep fragmentation and premature sleep curtailment due to disorders and lifestyle—demonstrate that cognitive deficits accumulate to severe levels over time without full awareness by the affected individual. Functional neuroimaging has revealed that frequent and progressively longer cognitive lapses, which are a hallmark of sleep deprivation, involve distributed changes in brain regions including frontal and parietal control areas, secondary sensory processing areas, and thalamic areas. There are robust differences among individuals in the degree of their cognitive vulnerability to sleep loss that may involve differences in prefrontal and parietal cortices, and that may have a basis in genes regulating sleep homeostasis and circadian rhythms. Thus, cognitive deficits believed to be a function of the severity of clinical sleep disturbance may be a product of genetic alleles associated with differential cognitive vulnerability to sleep loss.
PMCID: PMC3564638  PMID: 19742409
Neurobehavioral performance; sleep restriction; attention and executive function; functional neuroimaging; prefrontal cortex; thalamus; sensory processing areas; genetics
11.  Insomnia in school-age children with Asperger syndrome or high-functioning autism 
BMC Psychiatry  2006;6:18.
Asperger syndrome (AS) and high-functioning autism (HFA) are pervasive developmental disorders (PDD) in individuals of normal intelligence. Childhood AS/HFA is considered to be often associated with disturbed sleep, in particular with difficulties initiating and/or maintaining sleep (insomnia). However, studies about the topic are still scarce. The present study investigated childhood AS/HFA regarding a wide range of parent reported sleep-wake behaviour, with a particular focus on insomnia.
Thirty-two 8–12 yr old children with AS/HFA were compared with 32 age and gender matched typically developing children regarding sleep and associated behavioural characteristics. Several aspects of sleep-wake behaviour including insomnia were surveyed using a structured paediatric sleep questionnaire in which parents reported their children's sleep patterns for the previous six months. Recent sleep patterns were monitored by use of a one-week sleep diary and actigraphy. Behavioural characteristics were surveyed by use of information gleaned from parent and teacher-ratings in the High-Functioning Autism Spectrum Screening Questionnaire, and in the Strengths and Difficulties Questionnaire.
Parent-reported difficulties initiating sleep and daytime sleepiness were more common in children with AS/HFA than in controls, and 10/32 children with AS/HFA (31.2%) but none of the controls fulfilled our definition of paediatric insomnia. The parent-reported insomnia corresponded to the findings obtained by actigraphy. Children with insomnia had also more parent-reported autistic and emotional symptoms, and more teacher-reported emotional and hyperactivity symptoms than those children without insomnia.
Parental reports indicate that in childhood AS/HFA insomnia is a common and distressing symptom which is frequently associated with coexistent behaviour problems. Identification and treatment of sleep problems need to be a routine part of the treatment plan for children with AS/HFA.
PMCID: PMC1479331  PMID: 16646974
12.  Subject-Adaptive Real-Time Sleep Stage Classification Based on Conditional Random Field 
Sleep staging is the pattern recognition task of classifying sleep recordings into sleep stages. This task is one of the most important steps in sleep analysis. It is crucial for the diagnosis and treatment of various sleep disorders, and also relates closely to brain-machine interfaces. We report an automatic, online sleep stager using electroencephalogram (EEG) signal based on a recently-developed statistical pattern recognition method, conditional random field, and novel potential functions that have explicit physical meanings. Using sleep recordings from human subjects, we show that the average classification accuracy of our sleep stager almost approaches the theoretical limit and is about 8% higher than that of existing systems. Moreover, for a new subject snew with limited training data Dnew, we perform subject adaptation to improve classification accuracy. Our idea is to use the knowledge learned from old subjects to obtain from Dnew a regulated estimate of CRF’s parameters. Using sleep recordings from human subjects, we show that even without any Dnew, our sleep stager can achieve an average classification accuracy of 70% on snew. This accuracy increases with the size of Dnew and eventually becomes close to the theoretical limit.
PMCID: PMC2655818  PMID: 18693884
13.  Identifying sleep regulatory genes using a Drosophila model of insomnia 
Although it is widely accepted that sleep must serve an essential biological function, little is known about molecules that underlie sleep regulation. Given that insomnia is a common sleep disorder that disrupts the ability to initiate and maintain restorative sleep, a better understanding of its molecular underpinning may provide crucial insights into sleep regulatory processes. Thus, we created a line of flies using laboratory selection that share traits with human insomnia. After 60 generations insomnia-like (ins-l) flies sleep 60 min a day, exhibit difficulty initiating sleep, difficulty maintaining sleep, and show evidence of daytime cognitive impairment. ins-l flies are also hyperactive and hyper responsive to environmental perturbations. In addition they have difficulty maintaining their balance, have elevated levels of dopamine, are short-lived and show increased levels of triglycerides, cholesterol, and free fatty acids. While their core molecular clock remains intact, ins-l flies lose their ability to sleep when placed into constant darkness. Whole genome profiling identified genes that are modified in ins-l flies. Among those differentially expressed transcripts genes involved in metabolism, neuronal activity, and sensory perception constituted over-represented categories. We demonstrate that two of these genes are upregulated in human subjects following acute sleep deprivation. Together these data indicate that the ins-l flies are a useful tool that can be used to identify molecules important for sleep regulation and may provide insights into both the causes and long-term consequences of insomnia.
PMCID: PMC3654681  PMID: 19494137
Drosophila; behavior; sleep; insomnia; learning; genomics
14.  A Review on Genetics of Sleep Disorders 
One-third of population deal with sleep disorders which might be due to social, economic or medical problems. Studies on twins have indicated the role of genetic factors in these disorders. Monozygotic twins have a very similar hypnogram. A higher prevalence of some sleep disorders is reported in relatives of the patients with these disorders. Genes also affect sleep disorders as well as some other disorders at the same time. Sleep disorders can also influence the level of the personal and social functioning. Recent genetic advances have clarified the role of different genes in sleep disorders. The purpose of this article is to present a brief review about the role of genetic factors in some of the sleep disorders.
PMCID: PMC3939950  PMID: 24644464
Gene; Genetic study; Sleep disorders
15.  Relationship between sleep disturbance and recovery in patients with borderline personality disorder 
Journal of psychosomatic research  2013;74(4):278-282.
Patients with borderline personality disorder (BPD) frequently experience sleep disturbance, however, the role of sleep quality in the course of BPD is unknown. The purpose of this study was to evaluate the cross-sectional association between sleep quality and recovery status (symptomatic remission plus good concurrent psychosocial functioning) in a well-characterized cohort of patients with BPD to examine the role of sleep disturbance in the course of the disorder.
223 patients with BPD participating in the McLean Study of Adult Development (MSAD) were administered the Pittsburgh Sleep Quality Index (PSQI) as part of the 16-year follow-up wave. Sleep quality was compared between recovered (n=105) and non-recovered (n=118) BPD participants, including adjustment for age, sex, depression, anxiety, and primary sleep disorders.
Non-recovered BPD patients had significantly worse sleep quality than recovered BPD participants as measured by the global PSQI score (adjusted means 12.01 vs. 10.73, p=0.03). In addition, non-recovered BPD participants had longer sleep onset latency (adjusted means 39.20 vs. 28.11 minutes, p=0.04), as well as increased odds of using sleeping medication (adjusted OR 1.49, p=0.009) and experiencing daytime dysfunction as a result of their sleep disturbance (adjusted OR 1.48, p=0.008).
These results demonstrate an association between subjective sleep disturbance and recovery status among BPD patients. Further research is indicated to evaluate the mechanisms underlying sleep disturbance in BPD, and whether treatment of sleep complaints improves the symptomatic and psychosocial course of the disorder.
PMCID: PMC3603271  PMID: 23497827
borderline personality disorder; sleep; insomnia
16.  A Clinical Overview of Sleep and Attention-Deficit/Hyperactivity Disorder in Children and Adolescents 
The relationship between attention-deficit/hyperactivity disorder (ADHD) and sleep is a complex one which poses many challenges in clinical practice.
Studies of sleep disturbances in children with academic and behavioral problems have underscored the role that primary sleep disorders play in the clinical presentation of symptoms of inattention and behavioral dysregulation. In addition, recent research has shed further light on the prevalence, type, risk factors for, and impact of sleep disturbances in children with ADHD.
The following discussion of the multi-level and bi-directional relationships among sleep, neurobehavioral functioning, and the clinical syndrome of ADHD synthesizes current knowledge about the interaction of sleep and attention/arousal in these children.
Guidelines are provided, outlining a clinical approach to evaluation and management of children with ADHD and sleep problems.
PMCID: PMC2687494  PMID: 19495429
sleep; attention deficit hyperactivity disorder; sleep disorders; sommeil; trouble du déficit d’attention avec hyperactivité; troubles du sommeil
17.  Sleep Disturbances as Nontraditional Risk Factors for Development and Progression of CKD: Review of the Evidence 
Despite the high prevalence and enormous public health implications of chronic kidney disease (CKD), the factors responsible for its development and progression remain incompletely understood. To date, only a few studies have attempted to objectively characterize sleep in CKD patients prior to kidney failure, but emerging evidence suggests a high prevalence of sleep disorders, particularly obstructive sleep apnea. Laboratory and epidemiologic studies have shown that insufficient sleep and poor sleep quality promote the development and exacerbate the severity of three important risk factors for CKD, namely hypertension, type 2 diabetes, and obesity. In addition, sleep disturbances might have a direct effect on CKD through chronobiological alterations in the renin-angiotensin-aldosterone system and sympathetic nervous system activation. The negative impact of sleep disorders on vascular compliance and endothelial function may also have also have a deleterious effect on CKD. Sleep disturbances may therefore represent a novel risk factor for the development and progression of CKD. Optimizing sleep duration and quality and treating sleep disorders may reduce the severity and delay the progression of CKD.
PMCID: PMC3461247  PMID: 22727724
Sleep disorders; obstructive sleep apnea; chronic kidney disease
18.  Topographic and sex-related differences in sleep spindles in major depressive disorder: A high-density EEG investigation 
Journal of affective disorders  2012;146(1):120-125.
Sleep spindles are believed to mediate several sleep-related functions including maintaining disconnection from the external environment during sleep, cortical development, and sleep-dependent memory consolidation. Prior studies that have examined sleep spindles in major depressive disorder (MDD) have not demonstrated consistent differences relative to control subjects, which may be due to sex-related variation and limited spatial resolution of spindle detection. Thus, this study sought to characterize sleep spindles in MDD using high-density electroencephalography (hdEEG) to examine the topography of sleep spindles across the cortex in MDD, as well as sex-related variation in spindle topography in the disorder.
All-night hdEEG recordings were collected in 30 unipolar MDD participants (19 women) and 30 age and sex-matched controls. Topography of sleep spindle density, amplitude, duration, and integrated spindle activity (ISA) were assessed to determine group differences. Spindle parameters were compared between MDD and controls, including analysis stratified by sex.
As a group, MDD subjects demonstrated significant increases in frontal and parietal spindle density and ISA compared to controls. When stratified by sex, MDD women demonstrated increases in frontal and parietal spindle density, amplitude, duration, and ISA; whereas MDD men demonstrated either no differences or decreases in spindle parameters.
Given the number of male subjects, this study may be underpowered to detect differences in spindle parameters in male MDD participants.
This study demonstrates topographic and sex-related differences in sleep spindles in MDD. Further research is warranted to investigate the role of sleep spindles and sex in the pathophysiology of MDD.
PMCID: PMC3648867  PMID: 22974470
Sleep spindles; Major depressive disorder; High-density EEG
19.  Sleep problems and functional disability in children with functional gastrointestinal disorders: An examination of the potential mediating effects of physical and emotional symptoms 
BMC Gastroenterology  2012;12:142.
Sleep disturbances are increasingly recognized as a common problem for children and adolescents with chronic pain conditions, but little is known about the prevalence, type, and impact of sleep problems in pediatric functional gastrointestinal disorders (FGIDs). The objectives of the current study were two-fold: 1) to describe the pattern of sleep disturbances reported in a large sample of children and adolescents with FGIDs; and, 2) to explore the impact of sleep by examining the inter-relationships between sleep disturbance, physical symptoms, emotional problems, and functional disability in this population.
Over a 3-year period, 283 children aged 8–17 years who were diagnosed with an FGID and a primary caretaker independently completed questionnaires regarding sleep, emotional functioning, physical symptoms, and functional disability during an initial evaluation for chronic abdominal pain at a pediatric tertiary care center. A verbal review of systems also was collected at that time. Descriptive statistics were used to characterize the pattern of sleep disturbances reported, while structural equation modeling (SEM) was employed to test theorized meditational relationships between sleep and functional disability through physical and emotional symptoms.
Clinically significant elevations in sleep problems were found in 45% of the sample, with difficulties related to sleep onset and maintenance being most common. No difference was seen by specific FGID or by sex, although adolescents were more likely to have sleep onset issues than younger children. Sleep problems were positively associated with functional disability and physical symptoms fully mediated this relationship. Emotional symptoms, while associated with sleep problems, evidenced no direct link to functional disability.
Sleep problems are common in pediatric FGIDs and are associated with functional disability through their impact on physical symptoms. Treatments targeting sleep are likely to be beneficial in improving physical symptoms and, ultimately, daily function in pediatric FGIDs.
PMCID: PMC3527282  PMID: 23067390
Sleep; Functional disability; Functional gastrointestinal disorders; Pediatrics
20.  Study protocol: the sleeping sound with attention-deficit/hyperactivity disorder project 
BMC Pediatrics  2010;10:101.
Up to 70% of children with Attention-Deficit/Hyperactivity Disorder (ADHD) experience sleep problems including difficulties initiating and maintaining sleep. Sleep problems in children with ADHD can result in poorer child functioning, impacting on school attendance, daily functioning and behaviour, as well as parental mental health and work attendance. The Sleeping Sound with ADHD trial aims to investigate the efficacy of a behavioural sleep program in treating sleep problems experienced by children with ADHD. We have demonstrated the feasibility and the acceptability of this treatment program in a pilot study.
This randomised controlled trial (RCT) is being conducted with 198 children (aged between 5 to 12 years) with ADHD and moderate to severe sleep problems. Children are recruited from public and private paediatric practices across the state of Victoria, Australia. Upon receiving informed written consent, families are randomised to receive either the behavioural sleep intervention or usual care. The intervention consists of two individual, face-to-face consultations and a follow-up phone call with a trained clinician (trainee consultant paediatrician or psychologist), focusing on the assessment and management of child sleep problems. The primary outcome is parent- and teacher-reported ADHD symptoms (ADHD Rating Scale IV). Secondary outcomes are child sleep (actigraphy and parent report), behaviour, daily functioning, school attendance and working memory, as well as parent mental health and work attendance. We are also assessing the impact of children's psychiatric comorbidity (measured using a structured diagnostic interview) on treatment outcome.
To our knowledge, this is the first RCT of a behavioural intervention aiming to treat sleep problems in children with ADHD. If effective, this program will provide a feasible non-pharmacological and acceptable intervention improving child sleep and ADHD symptoms in this patient group.
Trial Registration
Current Controlled Trials ISRCTN68819261.
PMCID: PMC3022790  PMID: 21192797
21.  Sleep and allergic disease: A summary of the literature and future directions for research 
Atopic diseases, such as asthma and allergic rhinitis, are common conditions that can influence sleep and subsequent daytime functioning. Children and patients with allergic conditions from ethnic minority groups might be particularly vulnerable to poor sleep and compromised daytime functioning because of the prevalence of these illnesses in these groups and the high level of morbidity. Research over the past 10 years has shed light on the pathophysiologic mechanisms (eg, inflammatory mediators) involved in many atopic diseases that can underlie sleep disruptions as a consequence of the presence of nocturnal symptoms. Associations between nocturnal symptoms and sleep and poorer quality of life as a result of missed sleep have been demonstrated across studies. Patients with severe illness and poor control appear to bear the most burden in terms of sleep impairment. Sleep-disordered breathing is also more common in patients with allergic diseases. Upper and lower airway resistance can increase the risk for sleep-disordered breathing events. In patients with allergic rhinitis, nasal congestion is a risk factor for apnea and snoring. Finally, consistent and appropriate use of medications can minimize nocturnal asthma or allergic symptoms that might disrupt sleep. Despite these advances, there is much room for improvement in this area. A summary of the sleep and allergic disease literature is reviewed, with methodological, conceptual, and clinical suggestions presented for future research.
PMCID: PMC3576835  PMID: 22867694
Sleep; allergic disease; asthma; allergic rhinitis; atopic dermatitis
22.  Overlapping prefrontal systems involved in cognitive and emotional processing in euthymic bipolar disorder and following sleep deprivation: A review of functional neuroimaging studies 
Clinical psychology review  2012;32(7):650-663.
Prefrontal cortex (PFC) mediated cognitive and emotional processing deficits in bipolar disorder lead to functional limitations even during periods of mood stability. Alterations of sleep and circadian functioning are well-documented in bipolar disorder, but there is little research directly examining the mechanistic role of sleep and/or circadian rhythms in the observed cognitive and emotional processing deficits. We systematically review the cognitive and emotional processing deficits reliant upon PFC functioning of euthymic patients with bipolar disorder and in healthy individuals deprived of sleep. The evidence from two parallel lines of investigation suggests that sleep and circadian rhythms may be involved in the cognitive and emotional processing deficits seen in bipolar disorder through overlapping neurobiological systems. We discuss current models of bipolar highlighting the PFC-limbic connections and discuss inclusion of sleep-related mechanisms. Sleep and circadian dysfunction is a core feature of bipolar disorder and models of neurobiological abnormalities should incorporate chronobiological measures. Further research into the role of sleep and circadian rhythms in cognition and emotional processing in bipolar disorder is warranted.
PMCID: PMC3922056  PMID: 22926687
Bipolar Disorder; Sleep; Cognition; Emotional Processing; Prefrontal Cortex
Among older persons, sleep complaints in the form of insomnia and daytime drowsiness are highly prevalent and associated with adverse outcomes. The underlying mechanisms are linked to age-related declines in physiology, i.e., normal aging, and age-related increases in disease prevalence, i.e., usual aging. In this monograph, we describe how normal aging leads to less restorative sleep, characterized by reductions in homeostatic and circadian sleep, and to phase advancement of the sleep-wake cycle, characterized by older persons being more alert in the early morning but drowsier in the early evening. We also describe how usual aging leads to sleep complaints through reductions in health status, loss of physical function, and primary sleep disorders. Psychosocial influences are likewise described and their relevance to sleep complaints is discussed. We subsequently incorporate these aging-related changes into a conceptual model that describes sleep complaints as a consequence of multiple and interdependent predisposing, precipitating, and perpetuating factors, akin to a geriatric syndrome. We conclude our discussion by applying our conceptual model to the sleep-related care of an older person with insomnia and daytime drowsiness, and suggest that the diagnostic assessment consider, in addition to primary sleep disorders, multiple domains including medical, physical, cognitive, psychological, and social issues with the intent of developing an overall therapeutic plan and establishing long-term follow-up.
PMCID: PMC2785709  PMID: 17916123
insomnia; drowsiness; senescence
24.  Evaluating daytime alertness in individuals with restless legs syndrome (RLS) compared to sleep restricted controls 
Sleep medicine  2008;10(1):134-138.
Background and purpose
Restless Legs Syndrome (RLS) is a common sensorimotor disorder often associated with significant chronic sleep loss. Previous studies looking at the effects of sleep loss on daytime function in RLS individuals, using subjective reporting techniques have yielded mixed results. In this study we used more objective measures of alertness and compared RLS subjects who are off treatments and chronically sleep restricted to chronic sleep-restricted controls.
Subjects and Methods
The final sample consisted of 20 RLS subjects (10 male and 10 female) and 13 sleep-restricted controls (seven male and six female). Thirteen controls underwent a 14-day chronic partial sleep-restriction protocol in order to closely match the degree of chronic sleep loss reportedly experienced by untreated RLS patients. On the final day of the protocol each subject performed a morning and evening Suggested Immobilization Test (SIT) which served as a modified Maintenance of Wakefulness Test (MWT). RLS and control groups were compared for differences in alertness as measured objectively by the sleep latency on the morning and evening SITs.
The RLS subjects had a longer sleep latency on the morning and evening SIT than controls (t = 3.80, p = .001, U = 31.0, p < .001, respectively). Even after controlling for the potential arousal impact associated with increased leg activity, RLS individuals still demonstrated a higher degree of objective alertness (p = 0.023, p = 0.006, Fisher's exact test).
RLS subjects, despite having, if anything, greater sleep loss, displayed greater sustained alertness than sleep-restricted controls. Thus, the heightened degree of alertness demonstrated by RLS patients may be in contrast to the perceived impairment in mood, vigor, and vigilance commonly reported in previous studies.
PMCID: PMC2650846  PMID: 18226948
Restless legs syndrome; Sleep deprivation; Chronic sleep restriction; Polysomnogram; Sleep Latency; Suggested Immobilization Test (SIT)
25.  Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity 
The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA) axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB) display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment.
PMCID: PMC2902103  PMID: 20628523

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