Sleep in Psychiatric Disorders
Introduction
Sleep problems are commonly reported among children and adolescents with psychiatric disorders. Growing numbers of epidemiological studies in patients attending child psychiatric clinics have described a high prevalence of sleep-related disorders that include: bedtime refusal, fear of the dark, nightmares, night terrors, and restless sleep.1 Long sleep latencies, short sleep durations, frequent nocturnal awakenings, and restless sleep have all been shown to correlate with the severity of psychiatric symptoms in a diverse cohort of children with psychiatric disorders.2
Numerous surveys have indicated a strong association between sleep complaints and symptoms of emotional distress, depression, and anxiety in children.3–6 In a large community-based prospective study of 6-year-old children, 13% of those with trouble sleeping were found to have clinically elevated anxiety and depressive scores compared to just 3% of children without problems sleeping; at age 11, the percentage of children with anxiety or depressive symptoms increased to 29% and 4%, respectively.7
Adolescents with sleep problems have significantly elevated rates of depression, anxiety, low self-esteem, excessive worry, and irritability, as well as an increased likelihood of using alcohol, nicotine, and caffeine.8–12 A recent cross-sectional and prospective study of 12–18-year-olds found that 54% of adolescents with insomnia reported depressive symptoms, 26% had suicidal ideation, and 10% indicated a history of suicide attempts, with all frequencies higher than those found in a non-insomnia group (which were 32%, 12%, and 3%, respectively).13
Sleep in Early-Onset Major Depression
Major depressive disorder (MDD) is a severe and debilitating clinical condition that is often recurrent and associated with poor psychosocial, academic, and occupational outcomes. Approximately 2% of children and 8% of adolescents are affected by MDD with a male-to-female ratio of 1 : 1 in children and 1 : 2 in adolescents.14 Suicide is the most dramatic outcome of MDD and the third leading cause of death for people aged 15 to 24.15
Subjective sleep complaints are characteristic of MDD in adults and include: sleep initiation and sleep maintenance insomnia, early morning awakenings, non-refreshed sleep, disturbed dreams, and decreased total sleep time. A subset of adult patients with MDD present with hypersomnia and daytime fatigue. Objective polysomnographic (PSG) studies of adults with MDD yielded consistent findings with prolonged sleep onset latency, short rapid eye movement (REM) sleep onset latency, reduced slow-wave sleep, and increased sleep fragmentation.16 Furthermore, research data suggest that insomnia predicts relapse of depression in previously remitted patients,17 and that objectively measured prolonged sleep onset latency and short sleep duration, with or without complaints of insomnia, are risk factors for poor depression treatment outcome.18
Subjective Sleep Complaints in Early-Onset Major Depression
Early studies of sleep complaints in clinically depressed pre-adolescent children revealed that two-thirds of children with depression reported sleep onset and sleep maintenance problems and half suffered from terminal insomnia. Furthermore, their sleep complaints continued throughout the depressive episode with 10% of children experiencing insomnia after remission.19,20 In a large community sample of 1507 adolescents, 88.6% of those who met diagnostic criteria for major depression reported sleep disturbances.21 Interestingly, the 75.7% of adolescents who went on to develop a major depressive episode over a 12-month period had insomnia as an initial complaint. A more recent study assessed sleep-related symptoms among children and adolescents ages 7.3 to 14.9 years diagnosed with major depression using a structured diagnostic interview.22 Sleep complaints were present in 72.7% of the patients. Children and adolescents with sleep disturbances had more severe depression with higher rates of anxiety symptoms. In that same clinical sample, 53.5% of those with sleep complaints reported insomnia, 9% experienced hypersomnia alone, and 10.1% had both insomnia and hypersomnia (with that combination of symptoms seemingly associated with the most severe forms of depression).22
Sleep Complaints and Adolescent Suicide
Sleep disturbances, especially insomnia and nightmares, have been associated with increased rates of reported suicidal ideation and suicide attempts in youngsters.23–25 In the only known study that examined sleep disturbances in 15 to 19-year-old suicide completers, insomnia was 10 times more likely to have been reported in that group than it was in community controls. Furthermore, adolescents who completed suicide were five times more likely than controls to have exhibited insomnia in the week preceding death.26
An association between suicidality and sleep duration was examined using the Youth Risk Behavior Surveys from 2007 and 2009, which consist of school-based, nationally representative samples (n = 12 154 for 2007, n = 14 782 for 2009). Adolescents who reported sleeping ≤5 or ≥10 hours had a significantly higher risk for suicidality compared to those with a total sleep time (TST) of 8 hours. The largest odds ratios were found among the most severe forms of suicide attempt behaviors (such as those requiring treatment) with an odds ratio of 5.9 for a TST ≤4 hours and 4.7 for a TST ≥10 hours.27
In a 2011 prospective study of high-risk adolescents, Wong et al. compared 392 children (280 boys and 112 girls, 12–14 years old) from high-risk alcoholic families to controls.28 They found that having sleep problems at 12 to 14 years significantly predicted suicidal thoughts and self-harm behaviors at 15 to 17 years, even when controlling for other variables such as gender, parental alcoholism or prior suicidal thoughts. Interestingly enough, variables such as depression and substance-related problems at age 12 to 14 were not significant predictors. This study emphasized the importance of sleep assessment when screening for risk factors for suicidal behaviors in adolescents.
Objective Sleep Measures in Early-Onset Major Depression: PSG/EEG Studies
PSG characteristics of sleep have been examined in prepubertal children with major depression and have yielded inconsistent results. The early work by Puig-Antich and colleagues (1982) failed to reveal significant differences in any sleep variables between children with major depression and normal controls.19 Their findings were later supported by other studies that demonstrated no differences in PSG characteristics between children with MDD and healthy controls.29,30 However, when depressed children were recruited from inpatient facilities, reduced REM onset latencies, increased REM time, and increased sleep onset latencies were found in a subset of prepubertal children with MDD30,31 Based on such PSG characteristics, it was suggested that inpatient status, severity of MDD, and presence of other psychiatric comorbidities may influence sleep characteristics in pre-adolescent depressives. Over the years of PSG research, a prolonged latency to sleep onset has emerged as one of the more stable characteristics of sleep dysregulation associated with early-onset MDD.32
PSG characteristics have been examined much more extensively in adolescents with MDD. The first such study, which compared 13 depressed adolescents with 13 age-matched normal controls, revealed shorter REM onset latencies and greater REM densities in the depressed patients.33 At least one subsequent study found PSG abnormalities in early-onset MDD to be similar to those found in depressed adults.34 However, a few other studies failed to differentiate adolescents with MDD from normal controls based on REM sleep characteristics.35–37
In a more recent mixed-age group sample of children aged 7 to 17 years with either MDD or an anxiety disorder, subjective and objective sleep characteristics were similar in the MDD group and normal controls.38 When electroencephalographic (EEG) sleep measures during an episode were compared to those during recovery, 15–17-year-old adolescents with MDD demonstrated lower sleep efficiencies and REM latencies than controls, a reduction that remained unchanged even in remission, suggesting that EEG sleep changes are state-independent and represent a biological trait of MDD.39
The discrepancies between studies may be explained by the subtypes of depression, severity of clinical state, gender, age range of participants, and presence of anxiety, attention deficit hyperactivity disorder (ADHD), or other psychiatric symptoms.40,41
Based on the available research data, there seems to be a stronger association between subjective sleep complaints and depression than there is to objective instrumental measures of sleep and MDD. When both subjective and EEG sleep characteristics were examined in youngsters with MDD, there was no evidence of EEG sleep disruptions in children with depression compared to healthy controls, even in the presence of significant sleep-related complaints. What is even more interesting is that children with the highest rating of insomnias showed the highest sleep efficiencies according to PSG reports.42 Perception of sleep thus seems to be different in depressed individuals than in normal controls.
Objective Sleep Measures in Early-Onset Major Depression: Actigraphic Studies
Abnormal circadian rhythms were described in children and adolescents with depression compared to controls; these were characterized by blunted activity level with diurnal variations that did not peak until early evening.43,44 Armitage et al. found that among children (as opposed to adolescents) with MDD, there were sex differences noted, with damped circadian amplitudes seen only in girls.44
When children with depression were compared, by actigraphic study, both with normal children and ones with a history of abuse, the children who had been abused showed both the highest levels of nocturnal activity and the longest sleep onset latencies.45 The authors concluded that abuse has a more profound effect on sleep regulation than does depression alone.
Sleep in Early-Onset Bipolar Disorder
Bipolar disorder is a chronic severe psychiatric illness with a prevalence rate in the pediatric population of 1.8%.46 There are four types of bipolar disorder currently defined in the DSM-IV: bipolar-I disorder, bipolar-II disorder, bipolar disorder-not otherwise specified (NOS), and cyclothymia. Research studies in adults with bipolar disorder showed sleep problems to be associated with every phase of bipolar illness and usually include insomnia with reduced need for sleep during the manic phase, and insomnia with hypersomnia during depressed phase.47–50
Circadian and social rhythm dysfunction has been proposed as one of the pathophysiological mechanisms of bipolar disorder in adults.51 Although research on circadian rhythms in pediatric bipolar disorder is limited, some evidence exists that interpersonal and social rhythm therapy is beneficial to adolescents with bipolar illness.52,53 Interpersonal and social rhythm therapy is based on the belief that sleep deprivation, and disruptions of our circadian rhythms, may provoke or exacerbate symptoms commonly associated with bipolar disorder. This form of therapy uses methods from both interpersonal psychotherapy and cognitive-behavioral therapy to teach patients the importance of, and help them maintain in a regular fashion, their daily circadian rhythms and activity routines such as of eating and sleeping.
Sleep Complaints in Early-Onset Bipolar Disorder
Examinations of sleep complaints among different samples of children and adolescents with bipolar disorder-I, bipolar disorder-II, and cyclothymia revealed a weighted average of 72% of patients reporting a decreased need for sleep with symptoms of mania.54 Geller et al. compared the clinical characteristics of 7–16-year-old children and adolescents with bipolar disorder, ADHD, and healthy controls and found a reduced need for sleep in 40% of children with mania compared to only 6.2% of those with ADHD and 1.1% of normal controls.55 Thus, decreased need for sleep is one of the core symptoms of pediatric mania along with hypersexuality, elated mood, racing thoughts, and grandiosity.
When both parent and child reports of sleep problems were analyzed in patients with early-onset bipolar disorder, Lofthouse et al. found that 96.2% of children suffered from sleep disturbances related to manic, depressive, or comorbid symptoms during different phases of their illness.56 In their more recent web-based survey completed by parents of children with bipolar disorder, the following sleep problems were frequently reported: insomnia, daytime sleepiness, parasomnias, night wakings, bedtime resistance, anxiety, and sleep-disordered breathing.57 Nearly all children whose parents completed the web-based survey (96.9%) were affected by sleep disturbances that required either pharmacological or non-pharmacological sleep interventions.57,58
Diurnal variations of mood have been described in youth with bipolar disorder, with findings of evening acceleration of mood and energy and of delayed sleep onset with difficulty waking up in the morning. Nearly 30% of children exhibited elevated mood during the day switching into depression overnight.59
In their 2012 study, Baroni et al. evaluated sleep complaints in youth with bipolar-I and bipolar-NOS using a structured diagnostic interview (K-SADS-PL) during both manic and depressive episodes.60 At least one sleep symptom was reported by 84.3% of subjects: 71.4% of patients had insomnia during depressive episodes, 51.4% experienced decreased need for sleep during hypomania/mania, 22% of subjects reported circadian reversal, and 27% reported nocturnal enuresis. Decreased need for sleep correlated significantly with measures of global functioning, which suggests that manic symptoms, perhaps, have a more profound impact on global functioning in youth. There were no significant differences found in sleep characteristics between bipolar-I and bipolar-NOS, according to this study.
Objective Sleep Measures in Early-Onset Bipolar Disorder
There are only a few studies that have used PSG or actigraphic assessment of sleep in bipolar youth. In the first such study, published by Rao et al. in 2002, EEG characteristics of sleep were compared among three groups: adolescents with unipolar depression, those with bipolar disorder, and normal healthy controls.61 There were no differences in REM sleep found among the groups; however, those with bipolar disorder demonstrated increased amounts of stage 1 sleep and reduced percentages of stage 4 sleep.
In a study by Mehl et al., PSGs of children, whose results on the Child Behavior Checklist (CBCL) were suggestive of bipolar disorder, were compared with normal controls.62 Sleep measures of children with bipolar profile revealed reduced sleep efficiencies, reduced amounts of REM sleep, and increased numbers of nocturnal awakenings. On sleep questionnaires, parents of children with bipolar profile reported that their children had more problems with sleep onset, more restlessness, and more frequent nightmares and morning headaches than did controls. This study, however, was limited by the lack of validated clinical assessment of bipolar disorder in children participating in the study.
In a 2011 study, sleep was assessed in a small sample of adolescents with bipolar disorder, who were between mood episodes, and compared both to children with ADHD and to normal controls.63 Patients with bipolar disorder experienced their sleep as more fragmented and less restorative than their peers. However, actigraphy indicated the reverse, namely longer periods of sleep and fewer interruptions compared to their peers. Further research is needed to understand the discrepancy between self-perception of sleep and actigraphic sleep measures in this population.
Sleep in Childhood Anxiety Disorders
The presence and frequency of sleep disruption in children with anxiety disorders is among the highest seen in any form of child psychopathology. For example, in addition to rates of sleep problems above 90% in samples of anxious youth,64–66 group-based comparisons found that anxious youth experienced more frequent and more varied types of sleep problems than did their counterparts with ADHD.67 Conversely, children presenting with insomnia complaints were also most likely to have co-occurring anxiety disorders.2,68 Problems with sleep initiation, nighttime awakenings, nightmares, and bedtime resistance are among the problems most commonly reported.65,66
Retrospective reports of sleep are nonetheless subject to a range of potential limitations including reporter and recall biases. Far fewer studies have investigated the sleep of anxious youth prospectively. In one of the few studies to examine at-home sleep patterns, anxiety-disordered and healthy control children completed prospective 1-week sleep diaries. Later bedtimes, less sleep on weekdays, and more variable weekend sleep patterns were found among those with anxiety.69
Reports of sleep also have been found to vary based on informant. In particular, and in contrast to community samples where parents tend to underestimate child sleep problems,70,71 anxious youth reported fewer sleep problems than did their parents.66,72 Differential findings may be explained by greater parental awareness of, or sensitivity to, sleep problems in clinically anxious youth due to these problems commonly being covert or of an embarrassing nature (e.g., nighttime fears, requests to co-sleep, night terrors). It is also possible that anxious youth possess distorted perceptions about their sleep. Children with anxiety disorders have been found to underreport sleep disruption compared to objective sleep measures.73
In one of the few studies to examine PSG sleep patterns in these children, Forbes et al. used two nights of laboratory-based PSG to compare the EEG sleep patterns of three groups of children, all aged 7–17 years: those with anxiety disorders (including generalized anxiety disorder, panic disorder, separation anxiety disorder, or social phobia), those with depression, and those comprising a group of healthy controls.73 On both nights the anxiety group had more awakenings than the depressed group and less slow-wave (deep) sleep than depressed and control children. On the second PSG night anxious youth exhibited a prolonged sleep onset latency, whereas the latency to REM sleep decreased in both other groups. A greater percentage of missing data from night two was also reported in the anxious group. Thus, in addition to alterations in sleep architecture, results suggest that anxious children experience greater difficulty adapting to the sleep lab environment. Such data underscore a need for research examining objective sleep patterns in the home environment.
Generalized Anxiety Disorder
Diagnostic criteria and empirical data indicate that sleep plays an important role in pediatric generalized anxiety disorder (GAD). First, in addition to excessive and uncontrollable worry, DSM-IV criteria specifically include ‘difficulty falling or staying asleep’ as one of six possible physiological symptoms.74 Similar to rates in adults with GAD,75 a majority of youth experience difficulty sleeping, with rates as high as 94%.64–66 Other common sleep-related problems include nightmares and daytime sleepiness. Although a majority of research is based on parent report, one study found 87% of youth with a primary GAD diagnosis self-report difficulty sleeping and difficulty awakening in the morning, a greater proportion than seen in children with other primary anxiety disorders.66
In a study of EEG-based sleep patterns, Alfano and colleagues examined the sleep of prepubescent children (7 to 11 years) with GAD in comparison to a matched healthy control group based on one night of PSG.76 Anxious children studied were not depressed or taking any psychotropic medications at the time of the study. Children with GAD exhibited significantly longer sleep onset latency and reduced latency to REM sleep than controls. A marginally significant increase in REM sleep, and a decrease in sleep efficiency, also was found in the GAD group. Thus, although anxious children did not meet criteria for comorbid depressive diagnoses, objective sleep findings correspond in part with the trait-like sleep alterations found in clinically depressed and at-risk samples of adults.77–79 A shared genetic basis for GAD and depression, with overlapping of clinical features (i.e., negative affectivity) and/or of other neurobiological markers of risk, may serve to explain a similar overlap in sleep parameters.80
Separation Anxiety Disorder
Separation anxiety disorder (SAD) is characterized by developmentally inappropriate and excessive anxiety surrounding separation from major attachment figures.74 Two possible diagnostic symptoms of SAD are specific to sleep: persistent reluctance or refusal to sleep alone, and repeated nightmares involving themes of separation. Refusing to sleep alone is among the most common reasons for referral to an anxiety specialty clinic.81 Although empirical studies examining sleep problems in children with SAD specifically are limited, one study, based on parent and clinician reports, found that 97% of children with SAD had at least one sleep problem, which was more than that seen in children with social anxiety disorder (but not more than seen in children with GAD).65 Based on child reports, 60% of children with SAD reported difficulty sleeping.66 The most frequently listed sleep problems were insomnia, reluctance or refusal to sleep alone, and nightmares.65 Parents of children with primary SAD also reported that their children exhibited more parasomnias (including sleepwalking, bedwetting, and night terrors) than did parents of youth with social anxiety disorder.66 This last finding agrees with results, reported by Verduin and Kendall, that parasomnias commonly occur in the presence of SAD diagnosis.82
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