Mood Disorders

Chapter 130 Mood Disorders


Mood disorders, including major depressive disorder and bipolar disorder, are commonly associated with sleep disturbance, and sleep problems are part of the diagnostic criteria for these disorders. Although subjective complaints of insomnia are most common, hypersomnia and fatigue are also sometimes reported during periods of depression. Insomnia and hypersomnia are associated with an increased risk for the development or recurrence of mood disorder and increased severity of psychiatric symptoms. Polysomnographic studies of depressed patients have consistently revealed abnormalities in sleep architecture in comparison to controls, including decreased time in slow-wave sleep, reduced latency to rapid eye movement (REM) sleep onset, and disrupted sleep continuity. These associations provide insight into the neurobiological relationships between mood and sleep. Both subjective and objective sleep abnormalities commonly persist even during periods of clinical remission, making sleep disturbance a chronic problem for many patients with a history of a mood disorder. Depression thus must be assessed in any patient with a sleep complaint, and sleep problems often require specific and potentially ongoing treatment in persons with mood disorders.

Mood disorders are the second most common category of psychiatric disorders after anxiety disorders,1 and major depression alone affects at least 121 million persons worldwide. Moreover, the associated disability of mood disorders is among the highest reported for any disease: In 2000, bipolar disorder was in the top 10 causes of disability, and depression was the leading cause of disability and the fourth leading contributor to the global burden of disease. By 2020, depression is projected to be the second leading contributor to global burden of disease for all ages and both sexes.2 The impact of mood disorders includes eventual suicide in 15% of those affected, as well as increased morbidity and mortality from other illnesses.

Subjective sleep complaints are some of the most consistent symptoms associated with mood disorders. Disruptions of typical sleep patterns (insomnia, hypersomnia, or decreased need for sleep) are a core diagnostic criterion of mood episodes in the DSM-IV-TR3 (Boxes 130-1 and 130-2), reflecting their importance and prevalence in the presentation of these disorders. Sleep has been studied more extensively in patients with depression than with any other psychiatric disorder, and in addition to the subjective reports, there are objective, robust, and relatively specific changes in sleep architecture that can relate to the underlying neurobiology of depression.

Box 130-1

Adapted from the American Psychiatric Association: Diagnostic and statistical manual of mental disorders, 4th ed, text revision.

DSM-IV-TR Criteria for Major Depressive Episode

At least five of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either depressed mood or loss of interest or pleasure. Do not include symptoms that are clearly the result of a general medical condition or that are mood-incongruent delusions or hallucinations.

The symptoms do not meet criteria for a mixed episode.

The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The symptoms are not due to the direct physiologic effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).

The symptoms are not better accounted for by bereavement (i.e., after the loss of a loved one). The symptoms persist for longer than 2 months, or the symptoms are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

Box 130-2

Adapted from the American Psychiatric Association: Diagnostic and statistical manual of mental disorders, 4th ed, text revision.

DSM-IV-TR Criteria for Manic Episode

A manic episode is a distinct period of abnormality and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).

During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:

The symptoms do not meet criteria for a mixed episode.

The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

The symptoms are not due to the direct physiologic effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

Manic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of bipolar I disorder.

Classification and Diagnosis

Mood disorders are subclassified into depressive and bipolar disorders, based on the pattern of depressive and manic episodes.3 Diagnostic criteria for major depressive episodes are listed in Box 130-1 and include the characteristic finding(s) of depressed mood or anhedonia lasting at least 2 weeks. Recurrent major depression includes multiple, distinct major depressive episodes separated by at least 2 months of remission. In contrast, dysthymic disorder includes persistent but less-severe symptoms lasting for at least 2 years.

Manic episodes are described in Box 130-2 and are characterized by elevated or irritable mood lasting at least a week or requiring hospitalization. Hypomania has similar but less severe symptoms and may be less persistent. Mixed episodes occur when patients concurrently meet criteria for both manic and major depressive episodes for at least 1 week. Patients who experience one or more manic or mixed episodes have bipolar I disorder, and those with at least one lifetime episode each of major depression and hypomania have bipolar II disorder.

Major depressive episodes may be further categorized with one of several specifiers, including melancholic, atypical, or seasonal, each of which is at least partly related to sleep patterns. Melancholic depression includes a loss of pleasure in all, or almost all, activities; a lack of improvement in mood in response to normally pleasurable stimuli; and early morning awakening and diurnal variation in mood, with depression worse in the morning. Interestingly, patients with melancholic depression are more likely to have an improvement of depression with total sleep deprivation. Depression with atypical features includes significant mood reactivity to positive events, and weight gain and hypersomnia during periods of depression. Depressive episodes, in both major depression and bipolar disorder, can have a seasonal pattern, with a typical onset in the fall or winter and remission (or even mania or hypomania, when associated with bipolar disorder) in the spring or summer, suggesting a correlation with diurnal patterns of light exposure (Box 130-3).

Epidemiology and Risk Factors

Major depression is a common disorder and is reported to have a lifetime prevalence of 16.2% and a prevalence of 6.6% for the past 12 months in U.S. adults, with an increased risk (odds ratio [OR], 1.7) in women.4 The reason for increased rates of major depressive episodes in women is unclear, but it might include hormonal factors as well as differences in psychosocial stressors, and it is likely that the increased rates of both insomnia and depression in women are related. In contrast to major depression, bipolar I and II disorders each affect about 1% of the population (lifetime) and show no sexual predilection.5 Most bipolar disorder patients have at least one other DSM-IV comorbidity (such as substance use or anxiety disorders) and are more likely to have a persistent course and severe impairment.5 Major depression and bipolar disorders have an onset in early adulthood; the median age for major depression is 32 years and for bipolar disorders 18 to 20 years.5 Major depression and bipolar disorder both usually have recurrent episodes with recovery between episodes. However, increased number and severity of episodes and poorer interepisode recovery can lead to an overall worse prognosis, suggesting that chronic treatment may be beneficial for patients with recurrent illness.


Despite the devastating impact of mood disorders, relatively little is known about their etiology or pathophysiology. It has long been hypothesized that deficiencies in central nervous system monoaminergic systems, including noradrenergic, serotoninergic, and dopaminergic neurotransmission, are responsible for depression, and most effective antidepressant treatments, including medications and electroconvulsive therapy, increase intrasynaptic concentrations of monoamines.6,7 Antidepressants can also precipitate mania in susceptible persons, which supports the theory that mania may be related to increased monoaminergic activity.

Neural plasticity (via amino acid neurotransmitters, such as glutamate, and brain-derived neurotrophic factor [BDNF] levels) has been shown to play a role in depression.6,7 In addition to the role of neurotransmitter systems in mood pathophysiology, researchers have begun to elucidate the neuroanatomic, endocrine, and genetic factors involved.6,7 Studies of normal sleep and disrupted sleep also demonstrate clearly that most of the systems involved in mood regulation also appear to be involved in the regulation of sleep and wakefulness (see Chapter 7), suggesting that dysfunction in particular brain systems might lead to both mood and sleep abnormalities.

Clinical Features

Subjective Sleep Complaints

Problems with sleep are some of the earliest and most commonly reported symptoms of mood disorders. Specific sleep complaints include difficulty falling asleep, frequent nocturnal awakenings, early morning awakening, nonrestorative sleep, decreased or increased total sleep, and disturbing dreams. Insomnia, hypersomnia, or both are reported by approximately 75% of adults, children, and adolescents with major depression.8,9 Similarly, patients with bipolar disorder also often report insomnia or hypersomnia when they are depressed, but they are more likely to exhibit hypersomnia than unipolar patients.10 Little has been reported about sleep during (hypo)manic episodes, but diagnostic criteria (see Box 130-2) include a decreased need for sleep, usually accompanied by decreased sleep time.

Association of Sleep Disturbance and Mood Disorders

Sleep problems are extremely common in the general population and are often associated with psychiatric comorbidity. More than 35% of adults report some sleep problem.11 In the general adult population, 14% to 20% of persons with significant complaints of insomnia and about 10% of those with hypersomnia showed evidence of major depression, whereas rates of depression were less than 1% in those without sleep complaints.11,12 Additionally, the degree and duration of insomnia were positively correlated with more severe or recurrent major depression, or both.12 An assessment of the lifetime prevalence of sleep disturbance and psychiatric disorders in young adults also found greatly increased rates of major depression in persons with insomnia (OR, 3.8) in comparison to those with no sleep complaints (2.7%).13

The association between insomnia and depression may be even greater in clinical samples. More than half of patients with insomnia and medical or psychiatric patients evaluated by clinical interview in sleep disorders centers had a sleep disorder associated with mood disorder according to the International Classification of Sleep Disorders diagnosis.14 In children seen in general pediatrics clinics, insomnia and daytime fatigue were strongly correlated with elevated scores on the Child Behavior Checklist, and insomnia was particularly associated with symptoms of depression, anxiety, and attentional problems.15

Predictive Value of Sleep Complaints

It has historically been assumed that mood disorders cause changes in sleep patterns. Sleep disturbances, however, can also affect mood disorders, and epidemiologic data support this contention. Insomnia often precedes the onset of a first episode of major depression13 or mania10; in contrast, insomnia was more likely to occur subsequent to the onset of anxiety disorders.13 A similar temporal relationship between onset of insomnia and depression or anxiety has also been shown in adolescents.13

In prospective two-wave longitudinal studies, subjects who reported sleep disturbance at both the initial and 1- to 3-year follow-up interviews were much more likely to have developed new-onset major depression.16,17 The presence of insomnia or difficulty sleeping at an initial assessment is also associated with a long-term (>30 years) increased relative risk for development of major depression.18

In a meta-analysis of prospective studies on risk factors for depression among community-dwelling elderly persons, 57% of the risk for depression was attributable to insomnia, and insomnia was second only to recent bereavement in predicting depression.19 Women with more disrupted sleep also had more depression both before and after giving birth, and the presence of initial insomnia seemed to be the most relevant screening question for identifying women at risk for postpartum depression.20 Children who reported decreased amounts of sleep21 or insomnia13 were more likely to develop symptoms of depression and reduced self-esteem.

In patients who have had a previous episode of depression or mania, sleep changes remain a robust predictor of recurrent mood episodes, and their persistence is associated with a more severe course. Insomnia and fatigue were the most commonly reported symptoms preceding a recurrent major depression.22 In patients with bipolar disorder, an increase or decrease of 3 hours or more of sleep suggested imminent onset of a recurrent mood episode.23

Polysomnographic Findings

Major depression has been studied polysomnographically more than any other psychiatric disorder, and the majority of patients have shown objective sleep disturbances (reviewed in reference 26). Since at least the late 1960s, sleep electroencephalographic (EEG) changes have been extensively evaluated for their potential as biological markers of mood disorders. Objective sleep abnormalities in depression have been grouped into three general categories: disturbance of sleep continuity, deficits of slow-wave sleep (SWS, non–rapid eye movement [NREM] sleep stage 3), and abnormalities of REM sleep.27

Depressed patients showed prolonged sleep latency, increased wakefulness after sleep onset, and early morning awakening, which results in sleep fragmentation and decreased sleep efficiency. Patients with depression have decreased SWS, both as a fraction of total sleep and as SWS minutes. SWS loss is most significant during the first NREM period, but depressed patients appear to have reduced delta (1 to 4.5 Hz) EEG power and slow-wave counts throughout the night.28 The distribution of SWS during the night is abnormal, with a decreased ratio of slow-wave activity in the first relative to the second NREM period.29 The most robust finding in depression is a decreased REM sleep latency (time from onset of sleep to onset of REM sleep).26 Other REM sleep abnormalities include a prolonged first REM sleep period and increased REM density. Increased percentage of REM sleep has also been observed. Common sleep complaints and polysomnographic abnormalities are listed in Box 130-4.

Studies of subjects with bipolar disorder during either mania or depression have reported similar findings. During manic episodes, disrupted sleep continuity, shortened REM sleep latency, and increased REM density have been reported.30 Patients with bipolar depression and hypersomnia did not consistently show reduced REM sleep latency, and although they complained of daytime sleepiness, their sleep latency, as measured on the multiple sleep latency test (MSLT), was relatively normal.31 Results from the few studies investigating dysthymia have been variable, but they suggest that some of the characteristic sleep findings of major depression are present but not to the same extent.32

Sleep disturbances in patients with mood disorders are not limited to periods of acute depression or mania: Several studies have reported abnormal sleep parameters in patients during remission and during acute illness. Some sleep abnormalities may be more severe in acute versus remission phases, including increased REM density and reduced sleep efficiency.33 However, reduced REM sleep latency and decreased SWS can persist for prolonged periods in otherwise asymptomatic persons. Thus, sleep disturbances—particularly reduced REM sleep latency and SWS abnormalities—may be trait markers for some patients with mood disorders rather than simply indications of an acute state of illness. The persistence of sleep abnormalities suggests that sleep disturbance might indicate a biological susceptibility for depression and predate the illness, or sleep changes may be caused by depression and persist much longer than other affective symptoms.27 Additionally, first-degree relatives of subjects with major depression also show reduced REM sleep latency and SWS deficits, whether or not they have a personal history of a mood disorder,34 suggesting that sleep changes in depression include a hereditary component.

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Mar 13, 2017 | Posted by in NEUROLOGY | Comments Off on Mood Disorders
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