Sleep and Mood Disorders Among Youth

Research suggests that sleep plays an important role in the development, progression, and maintenance of mood disorder symptoms among children and adolescents.^1-4 While most of the extant research focuses on the relationship between insomnia and mood disorders, other sleep disorders such as delayed sleep phase, inadequate total sleep duration and bedtime resistance in younger children may play important roles in mood episodes.^{1, 4, 5} While there are no FDA approved medications specifically for sleep disorders in children and adolescents, fortunately there are effective behavioral sleep interventions. Research indicates that these behavioral interventions do effectively improve sleep in children and adolescents with depression, and indicate that sleep improvement is an important mediator of depression treatment outcome.^6-8 There is far less literature on Bipolar Disorders among youth and sleep and more research is needed to examine the potential role of a sleep intervention on the course of mood episodes among youth.

Defining sleep problems among children and adolescents.

While there are many sleep disorders which have been associated with depression, this review will highlight the three most common sleep disorders studied in the context of mood disorders among youth 1) insomnia, 2) delayed sleep phase, and 3) hypersomnia. Other sleep disorders/behaviors such as nightmares and obstructive sleep apnea are also important factors to consider, however they are not the focus of the present review.^{9, 10}

Insomnia

Most research on sleep disorders among youth has focused on insomnia. Insomnia is defined as difficulty initiating, maintaining or returning to sleep after an early morning awakening at least 3 nights per week for 3 months or more.¹¹ The DSM-5 also specifies that the difficulty sleeping must occur despite adequate opportunity for sleep.

Psychophysiologic (sometimes termed “conditioned”) insomnia is among the most common forms of insomnia in adults and may occur in older children and adolescents. Psychophysiological insomnia is characterized by heightened physiologic and emotional arousal related to sleep and the sleep environment. Children with psychophysiological insomnia often report anxiety about sleep, including maladaptive cognitions about the consequences of their sleep problems which often exacerbate their difficulties falling asleep.

In children, another distinct form of insomnia is behaviorally-based insomnia. It typically presents as bedtime resistance, characterized by prolonged sleep onset, and/or night wakings. Many children present with both bedtime resistance and prolonged nighttime awakenings which often require parental intervention and therefore disrupt parents’ sleep as well. This behaviorally-based insomnia is often related to either inconsistent or inadequate parental limit-setting or maladaptive sleep-onset associations. The limit-setting type of behavioral insomnia is characterized by bedtime resistance with verbal protests, and repeated requests/demands at bedtime (“curtain calls”). The delayed sleep onset resulting from bedtime resistance may result in inadequate sleep and subsequent moodiness and irritability the following day. The type of behavioral insomnia that is generally the result of certain sleep-onset associations is characterized by prolonged night waking and often results in insufficient sleep. In this disorder, the child has learned to fall asleep with specific sleep associations that typically require parental intervention, such as being held, rocked or fed. During the night, when the child awakens they are not able to return to sleep (“self-soothe”) unless those same sleep associations are available. The child then seeks the parents' attention to provide the necessary associations.

It is important to note that it is developmentally appropriate for some degree of transient bedtime resistance or insomnia to occur in children. To be considered a sleep disorder, the symptoms must occur frequently (at least 3 times per week) and persistently (for at least 3 months) and result in significant impairment of functioning in the child, parent(s), or family.

Insomnia is more common in children than in adolescents. Behavioral insomnia is most common in young children aged zero to five years but it can persist into school-age years.^{12, 13} Indeed, bedtime resistance has been reported in 10 to 15 percent of toddlers, and estimates indicate that 15 to 30 percent of preschool-aged children have insomnia.¹⁴ Among school aged-children (4 to 10 years of age), 25 to 40 percent report a sleep problem; 15 percent of these children have behavioral insomnia and approximately 11 percent have psychophysiologic insomnia.¹⁵ Approximately 11 percent of adolescents (13 to 16 years of age) report significant insomnia symptoms.¹⁶

Importantly, evidence indicates that insomnia tends to be chronic. Indeed, 88% of adolescents with a history of insomnia report current insomnia.¹⁶ Therefore, insomnia in children is an important problem to address.

Delayed Sleep Phase

Another important factor, particularly during adolescence, are sleep disorders affecting the circadian system; specifically the focus of this review will be on delayed sleep phase. Adolescence is associated with a biological shift in the circadian system at puberty in the direction of a delayed sleep phase, characterized by a preference for later sleep onset and offset, and sometimes referred to as an evening circadian preference or evening chronotype.¹⁷ This biological shift in the circadian system at puberty in the direction of a delayed sleep phase is often compounded by social changes during adolescence, such as less parental control, increased access to stimulating social activities (music, internet, text messaging etc.), increased academic demands at school, early school start times, increased social pressures and increased use of alcohol and drugs.^18-20 These social and hormonal influences can be synergistic in their effects, resulting in delayed bedtimes, less time available for sleep, and greater difficulty falling and staying asleep. Not surprisingly, adolescents report that they find it difficult to wake up for school and stay awake at school; they then attempt to “catch-up” on sleep on weekends, resulting in variability in timing of sleep and contributing to poor sleep quality. As a result, adolescents with delayed sleep phase also frequently experience insomnia, short sleep duration, poor sleep quality, and daytime sleepiness.

In community samples, rates of evening circadian preference or delayed sleep phase range between 30 to 40% of adolescents.^{1, 21} While this delay in circadian preference can be problematic for many youth, for youth that are able to adjust their sleep and wake times to accomodate this biologically driven delay there may be few adverse consequences. Indeed, the American Academy of Sleep Medicine²² and the Center for Disease Control and Prevention²³ recommend that middle and high schools implement start times no earlier than 8:30 A.M. to promote adolescents’ sleep needs, alertness, learning, safety, mental health and well-being.

Hypersomnia

Although not as clearly-defined or thoroughly-researched as insomnia and delayed sleep phase, hypersomnia (or hypersomnolence) is a crucial sleep disorder to consider among youth. Based on diagnostic criteria in the DSM-5, ICSD-2 and ICD-10, hypersomnia can be characterized by a combination of prolonged nighttime sleep episodes, increased nighttime wakefulness, frequent daytime napping, and, most notably, excessive daytime sleepiness (EDS).²⁴ However, excessive daytime sleepiness is neither synonymous with nor unique to hypersomnia—for example, in the ICSD-2, EDS is also listed as an essential feature of both narcolepsy and behaviorally induced insufficient syndrome, and is associated with a variety of syndromes (e.g., Kleine-Levin syndrome) and other sleep disorders, including insomnia and delayed sleep phase.²⁵ Because excessive daytime sleepiness is implicated in so many other diagnoses, idiopathic hypersomnia—that is, hypersomnia not explained by sleep deprivation, substance use, or other medical or psychiatric conditions—is significantly less common than EDS itself, which, as a symptom, is reported at fairly high rates among both adults and children.²⁶ Idiopathic hypersomnia is chronic, and patients tend to experience onset of symptoms during adolescence or early adulthood.²⁷ In addition to excessive daytime sleepiness combined with normal or prolonged (>10 hours) major sleep periods, patients with idiopathic hypersomnia often report a symptom known as “sleep drunkenness”, or waking up with confusion, automatic behavior, and repeated returns to sleep.²⁷

Epidemiological studies of hypersomnia have been inconsistent, focusing on the presence of one of two primary symptoms: excessive quantity of sleep or, more commonly, excessive daytime sleepiness.²⁵ Excessive daytime sleepiness among children and adolescents appears to be both prevalent and influenced by age: in pediatric clinics, EDS was twice as common among middle school-aged children than preschool-aged children,²⁸ and prevalence rates among preadolescents average to 4%, compared with 20% among high school seniors.²⁹ A confluence of factors—including physiologic changes that occur with maturation, sociocultural factors, and certain pathologies—predisposes teenagers in particular to excessive daytime sleepiness. ²⁹

Rates of sleep disorders among mood disordered youth

As noted above, the prevalence of insomnia, delayed sleep phase, and hypersomnia are quite common among community samples of children and adolescents, however, among samples of mood-disordered youth the prevalence rates are even higher. In a study of 553 youth (ages 7.3 to 14.9) with major depression,³⁰ 72.7% also reported a sleep disturbance (mostly insomnia). In adolescents with major depression, rates of insomnia vary between 33 and 51%.³⁰ While there are fewer studies that estimate rates of evening circadian preference among depressed youth, there are numerous studies which indicate a strong association between depression and evening circadian preference^31-33 with some studies of depressed youth indicating evening preference in as much as 81% of some depressed samples.³⁴ Based on prevalence rates alone, it is clear that the relationship between sleep disorders and depression among youth is important.

Importantly, in a review by Gregory and Sadeh³⁵ the authors note that the concurrent relationship between sleep problems and depression may change over time. Indeed, one study¹⁶ found that the association between sleep problems and depression was greater in children aged 11 years (odds ratio = 9.7) than aged 6 years (odds ratio = 4.7). Additionally, Gregory and Sadeh³⁵ reference a report³⁶ showing an increase in the magnitude of the association between sleep problems and depression from childhood (age 4 years, correlation = 0.39) to adolescence (age 13-15 years, correlation = 0.52). Gregory and Sadeh posit that one possible explanation for this trend is that sleep problems may be more common in children than adolescents and therefore perhaps more part of a typical development trajectory and less significant/indicative of a problem.

Bipolar disorder, with a weighted average prevalence rate across subtypes of 3.9% among children and adolescents, is also inextricably linked with sleep disorders.³⁷ Sleep disturbances associated with bipolar disorder may differ across manic, depressive, and euthymic states. Interestingly, diagnostic criteria suggest that individuals in manic states may experience a decreased need for sleep, and community studies show the prevalence of reduced sleep need to be between 21% to 87.5% among youth affected by bipolar disorder.³⁸ In a sample of 8 to 11 year-olds with early onset bipolar spectrum disorders, 82% report having depression-related sleep problems, with initial insomnia being the most pervasive.³⁹ Hypersomnia is also particularly salient in youth with bipolar disorder—a study by Parker and colleagues found hypersomnia to be present in 75% of bipolar disorderpatients younger than 25 years, but with increasing age, early morning awakening emerged as the dominant pattern instead.⁴⁰

Additionally, it is important to note that major depression, as well as subsyndromal depression, during adolescence and prepuberty appears to precede the development of bipolar disorder in emerging adulthood—this association has been replicated in a variety of prospective and retrospective studies.^41-43

Sleep problems may predict and predate the development of mood disorders.

The relationship between sleep problems and the development of depression can be linked back to the perinatal period. Research suggests that maternal perinatal sleep quality has the potential to influence vulnerabilities in children’s affective development. A large birth cohort study⁴⁴ found a prospective effect of prenatal insomnia symptoms on the social-emotional development of the child at 2 years of age, even after adjusting for confounding factors. However, the authors found the effect of perinatal insomnia on social-emotional child development to be mediated by postnatal factors—specifically, insomnia and depression symptoms—suggesting a potential chain of mechanisms characterizing this longitudinal process.⁴⁴ Indeed, in a review of the relationship between sleep quality and depression during the perinatal period,⁴⁵ Okun concluded that prenatal sleep disturbance is predictive of increased risk for development of postpartum depression.

Sleep characteristics in early infancy and toddlerhood appear to predict internalizing symptoms among toddlers and children. In a longitudinal study of 32,662 children,³ Sivertsen and colleagues found short sleep duration and nocturnal awakenings at 18 months to be significantly predictive, in a dose-response manner, of internalizing problems at 5 years. Similarly, a recent study by Morales-Muñoz and colleagues⁴⁶ also found short sleep duration and nocturnal awakenings in infancy to be prospectively related to internalizing symptoms in toddlers. Another large population-based prospective study⁴⁷ found dyssomnia (frequent nocturnal awakenings), parasomnia (the presence of nightmares), and short sleep duration in infancy and toddlerhood to be associated with an increased risk for depressive symptoms at 3 years. Results from several studies indicate a significant path from sleep problems among preschool aged children to internalizing problems at school age.^48-50

Among school-age children and adolescents, research indicates that insomnia likely precedes and predicts depressive episodes. A study of 289 twin pairs⁵¹ found that sleep problems at age 8 predicted depression at age 10. Importantly, the authors also found that genetic influences played a significant role in the prospective relationship between insomnia and depression in this sample.⁵¹ In another sample of youth age 13 to 16 with comorbid insomnia and depression,² insomnia preceded depression in 69% of the sample; the authors also found a significant association between prior insomnia and onset of depression even after adjusting for gender, race/ethnicity, and any prior anxiety disorder.² Data from the Great Smoky Mountains Study⁵² suggests a bidirectional relationship between sleep and depression, such that sleep problems during childhood predicted increases in the prevalence of later depression and anxiety symptoms in adolescents, and depression in childhood predicted later increases in sleep problems. Using a nationally representative sample of adolescents, our research group¹ examined specific sleep parameters that predict future depressive episodes. We found that late bedtime in middle school predicted more depression symptoms in young adulthood.¹ This study and others^{32, 33} suggest that evening circadian preference (indexed by late bedtime) may also be an important predictor of depression.

In a review,⁵³ Alvaro, Roberts, and Harris concluded, with caution, that the association between childhood sleep problems and depression is likely unidirectional. Indeed, several long-term longitudinal studies indicate that school-age childhood insomnia can predict adolescent and adult depression. As part of the British Cohort Study 1970, a prospective birth cohort with 30 years of follow-up (1975–2005), 7437 parents reported on the sleep difficulties of their 5-year olds (Greene et al., 2015).⁵⁴ These children were followed up over 30 years – and when the participants were aged 34 years they were asked if they had been treated for depression in the past year.⁵⁴ After adjusting for a number of potential cofounds (including maternal depression and sleep), severe sleep problems at 5 years was a significant predictor of depression at age 34.⁵⁴ In another sample of 490 children from a large longitudinal study,³⁶ analyses indicate that sleep problems at age 4 predicted behavioral/emotional problems in mid-adolescence. However, it is important to note that some researchers have failed to find evidence for this long-term relationship between sleep and depression. For example, Armstrong and colleagues failed to find a prospective relationship between insomnia persistence and depression over 15 years.⁵⁵

Relatedly, there is increasing evidence that insomnia is also a prospective risk factor for self-harm, suicidal ideation and suicidal behavior. In a longitudinal sample of adolescents, self-reported difficulties initiating or maintaining sleep at ages 12–14 significantly predicted suicidal thoughts and self-harm behaviors at ages 15–17.⁵⁶ In another sample of 101 youth selected for the presence of repeated self-harm behavior and high suicidality, self-reported sleep quality was significantly associated with elevated levels of overall self-harm, suicide attempts, nonsuicidal self-injurious behavior, and suicidal ideation at the same assessment, and predicted future self-harm within 30 days.³⁴

Taken together, sleep problems as early as the perinatal period may be an opportunity for early identification of those at risk for depression. Sleep problems may also be a potential prevention intervention target for youth at risk for depression.

Sleep disorders may also indicate a risk for the later development of bipolar disorders. Evidence from adult experimental sleep research studies indicate that induced sleep deprivation is associated with the onset of mania or hypomania. In a study by Wehr and colleagues⁵⁷ nine rapidly cycling adult patients with bipolar disorder who were in a depressed phase were sleep deprived for 40 hours (i.e., one night’s sleep deprivation), triggering mania or hypomania in seven of the nine individuals. In another study, Colombo and colleagues (1999)⁵⁸ recruited 206 depressed bipolar patients and randomized them to receive one night of total sleep deprivation followed by either a recovery night or a recovery night in combination with several medications (lithium salts, fluoxetine, amineptine, pindolol). The results indicated that after only one night of sleep deprivation, 9% of patients switched into mania or hypomania.⁵⁸ These results point to the possibility that chronic sleep deprivation could greatly influence relapse to mania.

Similarly, evidence suggests that the development of bipolar disorder is often preceded by sleep disturbance in childhood and adolescence. In a sample of offspring (ages 10-16 years) with at least one parent with bipolar disorder, youth with poor sleep had nearly twice the odds of developing bipolar disorder relative to good or variable sleepers.⁵⁹ Another study using a distinct sample of offspring with at least one parent with bipolar disorder found that over an average of 3.8 years, disturbed sleep patterns accounted for nearly a third (33.1%) of the explained variance in psychiatric symptom change; specifically, changes in mania, depression, anxiety, and mood lability were associated with shorter sleep duration, later sleep timing preference, poorer sleep continuity, and worsening daytime sleepiness.⁶⁰ In a community sample of 3021 young adults and adolescents, symptoms of trouble falling asleep and early morning awakening at baseline were predictive of subsequent onset of bipolar disorder.⁶¹ Additionally, according to a meta-analysis of sleep disturbance predicting the onset of bipolar disorder, sleep disturbances during childhood and adolescence frequently precede bipolar episodes—specifically, insomnia appears to precede the onset of manic episodes (with a frequency range of 48.8% to 54.8%), and both insomnia (14% to 66.7%), and hypersomnia (14% to 33.3%) appear to precede the onset of depressive episodes.⁶²

Given the evidence for a prodromal role of sleep disturbance in depression and mood episodes in bipolar disorder, sleep disturbance presents itself as a rich opportunity for early detection of and intervention for youth at risk for mood disorders. However, for youth who already have mood disorders, the data on the prospective relationship between mood disorders and the development of sleep disorders is reviewed below.

The relationship between mood disorders and the development of sleep disorders.

While the evidence reviewed above points to a unidirectional relationship between sleep problems and mood disorders, there is also evidence to suggest the reverse relationship—that is, mood disorders as risk factors for later sleep problems—as well as a bidirectional relationship between the two.

There is a body of perinatal depression research which supports the idea that maternal perinatal depression may predict sleep problems among children, although it is unclear to what extent this association is mediated by concurrent maternal depression. In the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort,⁶³ O’Connor and colleagues found that prenatal mood disturbance predicted offspring sleep problems at 18 and 30 months, independent of postnatal mood covariates. Similarly, results from the Finnish PREDO cohort showed that toddler-aged children of women with clinically significant depressive symptomology during pregnancy had, on average, shorter sleep duration, longer sleep latency, and more night awakenings (although this was fully mediated by concurrent maternal depressive symptomology) and were more likely to have a sleep disorder.⁶⁴ Interestingly, concurrent maternal depression added to the effect of prenatal depression on sleep disorders, such that children were most likely to have sleep disorders if their mothers had clinically significant depressive symptoms both during pregnancy and at the time of assessment.⁶⁴ Also utilizing the ALSPAC cohort, Taylor and colleagues⁶⁵ found evidence that maternal postnatal depression was associated with increased risk of sleep problems in adolescent offspring, suggesting that this association has the potential to persist beyond early childhood.

Most studies tend to support a unidirectional relationship where sleep problems precede and predict depression symptoms among children; however, a few studies have found a bidirectional relationship between sleep problems and depression. A longitudinal study⁶⁶ conducted among 2475 Norwegian children gathered from a primary care setting found a bidirectional relationship such that depression at age 4 was associated with insomnia at age 6 and insomnia at age 4 increased the risk for developing symptoms of depression at age 6. As mentioned earlier, in data from the Great Smokey Mountain Study conducted among 1420 children followed longitudinally from ages 9 to 16 years, Shanahan and colleagues found that sleep problems both predict and are predicted by depression.⁵²

In summary, while most of the longitudinal data seems to support the idea that sleep problems commonly predict and predate depression, there is also data to support a more complex and bidirectional model where depression can also predict later development of sleep problems. These studies support the idea that perinatal depression is likely a predictor of sleep problems among offspring and that depressed youth may also be at risk for developing future sleep problems; thus creating a vicious cycle between sleep problems and depression.

A review of the literature found no such studies indicating the mania may precede sleep problems. However, as noted earlier, depression symptoms during adolescence and the prepubertal period appear to precede the development of bipolar disorder in emerging adulthood.^41-43

Comorbidity between mood disorders and sleep problems is associated with more symptom severity.

Sleep problems are associated with greater depression symptom severity. In a sample of over 500 patients between the ages of 7 and 14.9 years,³⁰ sleep disturbance (observed in over 70% of the sample) was associated with greater depression severity and a greater likelihood of presenting depressed mood, irritability, distinct sadness, psychomotor agitation, fatigue, anhedonia, inappropriate guilt, weight loss, and diurnal variation. Emslie and colleagues⁶⁷ found that among children and adolescents with depressive disorders, insomnia symptoms, which were present in over half the sample, were associated with greater severity of specific depressive symptoms, including fatigue, suicidal ideation, physical complaints, and concentration. Similarly, among young adults with depressive symptoms, those reporting sleep disturbance had more anxiety symptoms than those without sleep disturbance.⁶⁸

In children and adolescents, there is a growing body of research documenting the connection between sleep and suicidal ideation and self-harm. One community-based study of over 600 school-aged children⁶⁹ found that significantly more children with self-harm behaviors reported subjective insomnia symptoms, even after adjusting for symptoms of depression. A cross-sectional, national and representative sample consisting of over 75,000 students (grades 7-12) in Korea⁷⁰ found that sleep disturbance was significantly associated with suicidal ideation in adolescents. In a study conducted by Goldstein, Bridge and Brent,⁷¹ sleep disturbances were assessed in 140 adolescent suicide victims and in 131 controls with a psychological autopsy protocol. The authors found that when rates of sleep disturbances were compared between groups, suicide completers had higher rates of overall sleep disturbance within both the last week and the current affective episode.⁷¹ In another study of Korean adolescents,⁷² weekend catch-up sleep duration (an indicator of insufficient weekday sleep and a common behavior among evening preference teens) was associated with suicide attempts and self-injury.

In summary, youth that present with both sleep problems and depression represent a particularly high risk group. These youth tend to have more severe depression and higher rates of self-harm and suicidality. Sleep problems may be a marker of disease severity in these patients.

To date, there is little to no published data on the relationship between sleep and disease severity among youth with bipolar disorder. One study conducted by Lunsford-Avery and colleagues⁷³ among youth with bipolar disorder who were entering a treatment trial found that sleep disturbance was associated with greater depression severity but not mania; Another study using an fMRI paradigm found that long and short sleep disturbance among youth with bipolar disorder was associated with less cognitive control under stress, an important factor for regulating impulsivity, which is characteristic of the disorder⁷⁴ and a correlate of disease severity.

Among adults with bipolar disorder, there is much more data to support the hypothesis that sleep problems correlate with disease severity. For example, in a sample of over 400 adults with bipolar disorder in a euthymic phase, shorter sleep duration was associated with increased mania severity, and greater sleep variability was associated with increased mania and depression severity.⁷⁵ A study of adolescents with bipolar disorder compared to control adolescents, found that increased awakenings and wakefulness on weekends predicted deprssion symtpoms among adolescents with bipolar disorder.⁷⁶ In the STEP-BD trial, conducted among over 2000 adults with bipolar disorder, short sleep duration was associated with a more severe symptom presentation, while both short and long sleep duration were associated with poorer function and quality of life compared to normal sleep duration.⁷⁷

Sleep problems may be associated with poor mood disorder treatment response.

Problematically, sleep problems may also be associated with poor response to both psychosocial and psychopharmacological antidepressant treatments. One study conducted among 166 depressed adolescents treated with either a 12-week course of sertraline, cognitive-behavioral therapy, or a combination, found that, across treatment groups, pre-treatment and persistent sleep disturbance was associated with lower response and remission rates.⁷⁸ In another study of 309 children and adolescents randomized to fluoxetine or placebo, the authors found similar antidepressant response in those with or without insomnia symptoms, however there was a significant difference by age group.⁶⁷ Among adolescents, those with insomnia symptoms were less likely to respond to fluoxetine than those without; while in children, the reverse was true (i.e., those with insomnia symptoms were more likely to respond to fluoxetine than those without insomnia).⁶⁷ While it is not clear why age moderated the association between disturbed sleep and response to fluoxetine, the authors suggest that this might be related to developmental differences in sleep architecture between depressed children and adolescents.⁶⁷ This finding may also be related to the point made by Gregory and Sadeh³⁵ that sleep problems are more common among children than adolescents and may therefore be less associated with risk. In a study of psychotherapy conducted by McGlinchey and colleagues (2017), the authors found that among depressed adolescents undergoing interpersonal psychotherapy for adolescents (IPT-A) or treatment as usual, sleep disturbance predicted more depression and interpersonal stress across treatments and led to a slower improvement in depression and interpersonal functioning.⁷⁹ Interestingly in a retrospective study of adults being treated for comorbid depression and insomnia, the authors found that childhood onset insomnia predicted worse treatment outcomes, underlying the importance of treating insomnia for a succesful course of depression treatment at all developmental stages.⁸⁰

Taken together, the data points to sleep problems among adolescents as a risk factor for poor depression treatment response. This data highlights the clinical importance of evaluating sleep problems among child and adolescent health care providers, especially among youth with comorbid depression.

Among adults and adolescents with bipolar disorder the data is more mixed. Youth with bipolar disorder who received either Family-Focused Treatment or a control therapy did not demonstrate improved sleep symptoms compared to the control treatment, however their mood symptoms were significantly improved.⁷³ Moreover, in a study of adults with bipolar disorder who participated in the STEP-BD trial, sleep duration was not a moderator of psychotherapy outcomes. However, this study did not look at other important sleep outcomes such as sleep irregularity or insomnia symptoms.⁸¹

Sleep problems may be associated with recurrence of mood episodes

Recovery from depression occurs in over 90% of depressed children and adolescents within 1 to 2 years.^{82, 83} However, once recovered, depressed children and adolescents experience high rates of recurrence of their depression. When re-evaluated 6 to 7 years later, depression remained a problem in 25% to 50% of youth, and a new episode of depression was reported in 54% to 72% of depressed children and adolescents followed for 3 to 8 years.^84-89

In adults and adolescents, insomnia is the most common residual symptom in remitted depression.^90-92 Moreover, adult data points to insomnia as an important predictor of recurrent depressive episodes.^93-95 In adolescents and children, there is less evidence for insomnia as a predictor of recurrence; however, one study providing evidence that sleep disruption may be a predictor of depression recurrence is highlighted here. Emslie and colleagues (2001) conducted a naturalistic 1 year follow-up on 113 depressed children and adolescents.⁹⁶ Using sleep polysomnography, the authors found that decreased sleep efficiency and delayed sleep onset (both indices of insomnia symptoms) at baseline predicted depression recurrence at 1 year follow-up.⁹⁶ More research is needed in children and adolescents to further investigate sleep problems as a risk factor for depression recurrence.

Results from samples of adults and youth with bipolar disorder similarly find that sleep problems are associated with mood episode reocurrence. Results from one study of youth with bipolar disorder indicated that sleep impairment and severity of manic and depressive symptoms were significantly intercorrelated over a two year period following treatment for mood symptoms.⁷³ As noted earlier, in adults with bipolar disorder enrolled in the STEP-BD trial for whom follow-up data was available, shorter sleep duration was associated with increased mania severity, and greater sleep variability was associated with increased mania and depression severity over a 12 month period.⁷⁷

Treatment of comorbid mood disorders and sleep problems.

Given, the severity and clinical implications of samples of depressed youth with comorbid sleep problems, the natural conclusion is to address both conditions with evidence-based psychotherapy and psychopharmacology. In the Treatment of Resistant Depression in Adolescents Study (TORDIA),⁹⁷ 334 treatment-resistant adolescents with depression received one of the four treatment strategies in a two-by-two balanced factorial design: (a) switch to another SSRI; (b) switch to venlafaxine; (c) switch to another SSRI plus cognitive behavioral therapy (CBT); or (d) switch to venlafaxine plus CBT. Those adolescents who received pharmacological treatment for sleep difficulties showed a poorer response rate than did those who did not receive medication for sleep, indicating that non-pharmacological therapies may be a preferable first line of treatment for adolescents with treatment resistant depression receiving antidepressant pharmacotherapy.⁹⁷

Cognitive Behavioral Therapy for Insomnia (CBT-I) is the first line recommended treatement for insomnia in adults. Numerous studies have demonstrated its effectiveness in treating insomnia with and without medical and psychiatric comorbidities. Several systematic reviews and meta-analyses^{7, 8, 98} focused on the effectiveness of CBT-I in children and adolescents have found that CBT-I can effectively improve sleep in school-age children and adolescents and that improvements are maintained over time.

In the preparation of this review, only one trial that tested concomitant treatment of depression and insomnia among adolescents was identified. The study compared the combination of CBT for depression (CBT-D) plus CBT-I to CBT-D plus sleep hygiene control therapy for insomnia among adolescents with comorbid insomnia and depression; the authors found no difference in rates of recovery from depression between the two conditions.⁶ However, when limiting the analysis to those who remitted from depression, the researchers found a trend for faster remission among those in the CBT-I condition,⁶ indicating that sleep improvement does play an important role in depression remission. Interestingly, this mirrors the findings in adult trials of depression treatment augmentation with CBT-I.^99-101 More research is needed in this important domain to identify potential moderators of depression treatment outcome among youth with comorbid depression and sleep problems.

In summary, while sleep pharmacotherapy may be contraindicated in some samples of youth with comorbid depression and sleep problems, CBT-I is an effective psychosocial intervention for improving insomnia symptoms among youth. However, while sleep improvement appears to be an important mediator of depression treatment among youth with depression and sleep problems, augmenting antidepressant treatment (psychosocial or pharmacological) with CBT-I may not necessarily improve depression outcomes. Of note, individuals with delayed sleep phase (who also very commonly have insomnia) have been left out of many of these trials^{6, 100, 102} due to concerns that CBT-I does not adequately address circadian concerns. As noted earlier, delayed sleep phase is a very common concern among adolescents and particularly among depressed adolescents.^{1, 17, 32} A paper published by our group provides some evidence from the adult literature that those with a delayed sleep preference and depression may be at risk for poor depression treatment response unless their sleep problems are addressed.¹⁰³

There are no studies conducted to date that directly address treatment of sleep disturbance among youth with bipolar disorder and there is only one trial of CBT-I among adults with bipolar disorder. This study, conducted by Allison Harvey and colleagues, found that relative to a psychoeducation condition, CBT-I for Bipolar Disorder (CBTI-BP) reduced insomnia severity and led to higher rates of insomnia remission at posttreatment and marginally higher rates at 6 month follow-up, indicating that CBTI-BP is safe and effective for patients with bipolar disorder.¹⁰⁴ Moreover, during the 6-month follow-up, the CBTI-BP group had fewer days in a bipolar episode (3.3 days vs. 25.5 days), experienced a significantly lower hypomania/mania relapse rate (4.6% vs. 31.6%) and a marginally lower overall mood episode relapse rate (13.6% vs. 42.1%) compared with the control group.¹⁰⁴ In summary, this study indicates that CBTI-BP is effective for insomnia among patients with bipolar disorder and may also reduce the frequency and intensity of mood episodes among patients with bipolar disorder. The authors recommend that practitioners should encourage regularity in sleep and wake times as a first step in treatment, and carefully monitor changes in mood and daytime sleepiness throughout the intervention.¹⁰⁵ However, it should be noted that this is the only study to date to specifically test CBT-I in patients with bipolar disorder and the results should be replicated.

Summary

In conclusion, sleep problems play an important role in the development, progression, and maintenance of unipolar and bipolar depression symptoms among children and adolescents. Identification of sleep problems as early as maternal perinatal insomnia may predict and predate depression among youth. Depression prevention through the early identification and treatment of sleep problems is an important future direction for research. Data suggests that children and adolescents who go on to develop comorbid mood symptoms and sleep problems represent a particularly high-risk group. Children and adolescents with comorbid mood symptoms and sleep problems tend to have more severe depressive symptoms, higher rates of self-harm and suicidality, and their depression symptoms tend to be less responsive to treatment. Even when depression and bipolar disorder treatments successfully improve mood symptoms, sleep problems tend to be among the most common residual symptoms and, if untreated, may be associated with recurrent depression and/or mania. Treatment research supports the idea that sleep problems can be improved through CBT-I among youth with and without depression. Although limited, the treatment research also indicates that, while CBT-I may not significantly augment depression treatment outcomes, sleep improvement is an important mediator of depression treatment outcomes. While there is no CBT-I data among youth with bipolar disorder, adult data suggests that CBTI-BP may improve both insomnia and mood symptoms among adults with bipolar disorder. Moreover, more research is needed on sleep problems which have been underevaluated and undertreated such as delayed sleep phase.

Synopsis.

The authors sought to review the literature on mood disorders and sleep disorders among children and adolescents. Research suggests that sleep plays an important role in the development, progression, and maintenance of mood disorder symptoms among children and adolescents. Sleep problems as early as maternal perinatal insomnia may predict and predate depression among youth. Children and adolescents who develop comorbid mood disorders and sleep problems represent a particularly high-risk group with more severe mood episode symptoms, higher rates of self-harm and suicidality, and less responsivity to treatment in some cases. Treatment research supports the idea that sleep problems can be improved through behavioral interventions.

Key Points.

• Evidence indicates that sleep problems often predict and predate the development of mood disorders.

• Rates of sleep disorders among mood disordered youth are high and comorbidity between mood episodes and sleep problems are associated with more severe mood episodes.

• Sleep problems are associated with poor depression treatment response and may be associated with recurrence of mood episodes episodes

• CBT-I is an effective psychosocial intervention for improving insomnia symptoms among youth

• Sleep improvement appears to be an important mediator of depression treatment among youth

Clinics Care Points.

• Sleep problems such as delayed sleep phase, hypersomnia and insomnia should be evaluated in clinical care for both the treatment and prevention of mood symptoms among youth.

• Youth who present with comorbid mood and sleep problems are a particularly high risk group.

• CBT-I is an effective treatment for sleep problems among youth with and without depression.

• If left untreated, sleep problems are among the most common residual symptoms following mood episode remission and are likely a risk factor for mood episode recurrence.