Sleep and sleep disturbance in generalized anxiety disorder
Sleep disturbance is included as one of the diagnostic features of GAD. GAD is char-acterized by generalized and persistent symptoms of anxiety that are driven by worry, which lasts for at least 6 months. The diagnosis of GAD requires the presence of three of the six anxiety-associated symptoms, including easily fatigued, restlessness, poor concentration, irritability, muscle tension, and sleep disturbance [5].
Survey studies have shown that about 50–70% of patients with GAD experience sleep disturbances [7–9]. Similar to primary insomnia, common sleep complaints in GAD are difficulty falling sleep, difficulty staying asleep and restless and unrefresh-ing sleep. Their sleep disturbances often become a subject of their obsessive worry, particularly around bedtime. Although nightmares are not one of the most common sleep complaints in GAD, one study showed that the frequency of disturbing dreams was associated with GAD symptoms in adolescences [10]. Several studies have ex-amined sleep in GAD patients with polysomnographic (PSG) recordings. In general, the findings were consistent with the patients’ subjective complaints. PSG sleep of drug-free GAD patients are characterized by increased sleep onset latency, increased wake time after sleep onset, reduced total sleep time, and decreased sleep efficiency when compared to healthy individuals. The distribution of different sleep stages across the night, however, did not show remarkable and consistent abnormalities across studies [11–13].
Sleep and sleep disturbance in panic disorder
Patients with panic disorder suffer from episodes of acute anxiety associated with several somatic symptoms such as tachycardia, chest pain, heart palpitations, and gastrointestinal discomfort, accompanied by the impression that they are going to die.
Patients are diagnosed as panic disorder with agoraphobia when they have “anxiety about, or avoidance of, places or situations from which escape might be difficult (or embarrassing) or in which help may not be available in the event of having a panic attack or panic-like symptoms” [5]. Panic attacks may occur during the daytime as well as during sleep.
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The studies on subjective sleep complaints in patients with panic disorder have not obtained consistent results. One study showed that 68% of patients with panic disorder reported moderately to severely impaired sleep, compared to only 15% of healthy controls, and 26% of panic disorder patients complained of frequent awak-enings, compared to none in healthy controls [14]. Another study, however, did not find significantly higher rate of sleep complaints in patients with panic disor-der than in normal controls [15]. The findings on PSG sleep in patients with panic disorder are also not consistent across studies. Different PSG sleep features found included increased sleep onset latency, decreased total sleep time [16, 17], decreased sleep efficiency [16–18], decreased stage 4 sleep [18], and increased movement time [19, 20]. One study reported no remarkable findings [21].
Panic attacks may occur during sleep at night. Nocturnal panic attacks that occur recurrently have been reported in about 18–45% of patients with panic disorder [21–23]. A study using an ambulatory monitoring system also confirmed that 18% of panic attacks occurred during sleep [24]. Patients usually awake abruptly from sleep with physical symptoms similar to their daytime panic attacks. Patients frequently experiencing nocturnal panic attacks may have a fear of going to bed and eventually develop insomnia [25]. PSG studies showed that the attack episodes usually occur following stage 2 or stage 3 sleep [16]. It has been suggested that the presence of sleep panic attacks may define a subtype of panic disorder. These patients were shown to experience early difficulties with anxiety and have higher co-morbidity with affective and anxiety disorders [26]. It has also been proposed that a nocturnal panic attack is a marker of a more severe panic disorder [27]. However, there is not enough evidence to support either of these points of view.
The mechanisms that result in nocturnal panic attacks are not yet fully clear.
Daytime panic attacks have been theorized to develop and be maintained by various psychological and physiological factors, such as hypersensitivity to somatic reactions and bodily sensations, conditioned anxiety responses, catastrophic misinterpretations of the somatic reactions, and anticipation of dangers [28]. Since the psychological or cognitive aspects of panic are presumed to be relatively absent during sleep, nocturnal panic attacks should result more from an endogenous physiological mechanism.
Proposed possible triggering mechanisms include changes of autonomic functioning [16, 18] and breathing regulation [29, 30] during sleep. One hypothesis suggests that nocturnal panic results from the combination of CO2hypersensitivity and the increase of CO2 pressure that usually occurs during sleep. To test this hypothesis, a study measured the baseline end-tidal CO2level and responses to forced hyperventilation and CO2 inhalation challenges in patients with nocturnal panic attacks, and those who experienced daytime attacks only. The results did not support this hypothesis, and showed no differences between these two groups in their end-tidal CO2levels and the frequencies of panic attacks induced by the procedures [23]. Studies have also examined the role of cognitive factors (i.e. , misappraisal of bodily sensations as threatening) in nocturnal panic attacks. It was shown that fake feedback signals during sleep, when they were believed to indicate unusual changes of arousal levels, led to more incidences of panic attacks than when they were believed to signal expected fluctuations of arousal level during sleep [31, 32]. The results suggest that cognitive
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factors may still contribute to nocturnal panic attacks in spite of the minimization of cognitive processes during sleep.
Since patients with panic disorder, in general, are more sensitive to bodily sensa-tions [28], sleep pathologies that lead to arousals and somatic reacsensa-tions may trigger panic attacks during sleep. Irregular breathing patterns and sleep apnea events have been shown to be increased in patients with panic disorder [30, 33]. These respira-tory events may result from an obstruction of the upper airway during sleep or be attributable to altered brainstem sensitivity to CO2[30]. Symptoms of sleep apnea, such as shortness of breath, feeling of choking, chest discomfort and autonomic re-actions to the apnea, are very similar to the features that characterize panic attacks.
These symptoms may possibly provoke the nocturnal panic attacks [34]. It is impor-tant to rule out sleep apnea syndrome with PSG when evaluating panic patients with predominantly nocturnal attacks.
Sleep and sleep disturbance in post-traumatic stress disorder
PTSD is defined by clusters of symptoms as the consequence of a profound traumatic event. The symptoms include the re-experiencing of the traumatic event (including nightmares), increased arousal (including insomnia), and avoidance of stimuli asso-ciated with the trauma [5]. Survey studies also reported that insomnia, nightmares and anxiety arousal are common sleep symptoms in patients with PTSD [35–37]. The content of the disturbed dreams and associated emotions are usually similar to the experiences of the traumatic event. It has been hypothesized that the memory of the traumatic event, by repeatedly stimulating the hippocampus and amygdala (kindling phenomenon), may be imprinted in the central nervous system and re-experienced in the nightmares [38]. The insomnia may in one way reflect the increased overall arousal, and in another way, result from the fear of sleep due to frequent disturbed dreams. However, the insomnia can be persistent and continue despite the remission of both nightmares as well as hypervigilance after treatment with cognitive behavior therapy for PTSD [39]. This implies that the insomnia may have been precipitated by PTSD originally, and with the development of subsequent sleep-specific pathologies the sleep disturbance may be perpetuated.
PSG studies on chronic PTSD patients have shown inconsistent results. Some studies reported no evidence of disturbances in sleep initiation or maintenance [40–42]; other studies showed decreased sleep efficiency and increased awakening [43, 44]. PTSD nightmares typically occurred during episodes of REM sleep, al-though some studies reported occurrences in NREM sleep [41, 43, 45–49]. Alal-though no typical pattern of REM sleep abnormality has been consistently reported in chronic PTSD patients, various features in REM sleep have been identified in different stud-ies, including increased eye movements [41, 50], increased phasic muscle activations [51], increased brief arousals [52], and increased awakening with and without dream recall [43]. Furthermore, nocturnal awakenings were found to be higher in PTSD patients with frequent nightmares than in idiopathic nightmare sufferers [53]. Taken together, all of these findings suggest an increased arousal level or decreased arousal threshold during REM sleep in patients with chronic PTSD [43, 54].
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Studies also compared the PSG sleep of victims of traumatic events who subse-quently developed PTSD with those who did not. Development of PTSD symptoms was found to be associated with a shorter average duration of REM sleep and more periods of REM sleep [55] as well as a higher sympathetic activation during REM sleep as measured by heart rate variability [56]. The authors hypothesized that the development of PTSD is associated with increased arousal and, possibly, elevated noradrenergic activity during REM sleep.The rate of sleep-disordered breathing has also been found to be elevated in patients with PTSD [57]. As in the case of panic disorder, nocturnal symptoms of sleep apnea can be confused with or exacerbate the symptoms associated with disturbed dreaming and anxiety arousals in patients with PTSD. The coexistence of sleep apnea syndrome may complicate the evaluation and management of PTSD.
Sleep and sleep disturbance in obsessive-compulsive disorder
Obsessive-compulsive disorder (OCD) is characterized by the presence of obsessions and compulsions. Obsessions are images, ideas, thoughts or impulses that enter the patient’s mind repeatedly and that are recognized as irrational by the patient.
Compulsions are repetitive or stereotyped behaviors that are performed in response to a specific obsession to prevent the occurrence of an unlikely event or to prevent discomfort [5].
OCD patients report only limited sleep complaints, most frequently difficulty falling asleep and early morning awakening [15]. They seldom present with sleep disturbances as their primary concern. The findings of PSG sleep, performed in pa-tients with OCD, are inconsistent across studies. An early study showed that the sleep abnormalities in patients with OCD generally resembled those of an age-matched group of depressed patients, with decreased total sleep time, reduced stage 4 sleep and shortened REM latency as the primary features [58]. More recent studies, how-ever, reported no sleep abnormalities except for a decrease in sleep efficiency [59, 60]. It is conceivable that the abnormalities of sleep architecture in the earlier study was related to the co-morbid condition of depression [61].
Sleep and sleep disturbance in social phobia
Social phobia is characterized by phobic anxiety and resulting avoidance of so-cial or performance situations [5]. Generally speaking, it is not unusual for patients with social phobia to complain of sleep difficulties; however, sleep disturbances are usually not the primary complaint of phobic patients. Social phobia can further be classified into two subtypes: generalized/pervasive type and discrete/circumscribed type. Patients with generalized social phobia reported relatively more frequent sleep disturbance, with significantly poorer sleep quality, longer sleep latency, and more severe daytime dysfunction [62]. In addition, 70–80% of patient with social phobia may have co-morbid conditions, such as depression and substance abuse [63]. Social phobia patients with these co-morbid disorders tend to have higher rates of sleep com-plaints, such as increased sleep latency, sleep fragmentation and nightmares. PSG
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study of patients with social phobia has been limited. The one PSG study showed no remarkable findings in patients with social phobia. All measures of sleep architecture were found to be comparable to sleep of control subjects [64].
Sleep in mixed anxiety-depressive disorder
Although anxiety disorders and depression are in general considered to be different diagnoses with different pathogeneses, the coexistence of symptoms of both disor-ders is very common in clinical patients. Research has shown that the rate of anxiety symptoms in depressive patients is as high as 60% . An epidemiological study in the community also reported that 10% of participants with depression symptoms also reported symptoms of anxiety disorders [65]. According to the DSM-IV, these patients, if not fulfilling the diagnostic criteria of either diagnosis, are classified as mixed anxiety-depressive disorder as a type of anxiety disorder not otherwise speci-fied (NOS) [5]. Whether this condition is a milder form of depressive disorders or a subtype of anxiety disorders is still at issue [66, 67]. It has been well-documented that patients with major depression have some specific manifestations in their PSG sleep, including decreased REM sleep latency, increased REM density in the first REM period, and decreased slow wave sleep. These PSG markers were thought to indicate specific neurochemical abnormalities in depression [68, 69]. The possibility of us-ing the PSG to differentiate anxiety and depressive disorders in patients with mixed symptoms has been examined in some studies. Although GAD patients, similar to de-pression patients, were shown to have prolonged sleep onset latency and decreased slow wave sleep, they do not usually have shortened REM latency and increased REM density, as shown in patients with depression [11, 12, 70]. Studies showed that patients with symptoms of both anxiety and depression had sleep architecture similar to GAD patients, and were differentiated from patients with depressive disorders [71, 72]. However, there are also studies reporting sleep architecture in OCD as similar to those in depression patients, although this may be attributable to the co-morbid condition of depression [58, 61].