Psychiatric Co-morbidity
by Ruth Benca


INTRODUCTION
    Psychiatric disorders account for the largest diagnostic category for patients with sleep complaints. Factors which may account for the strong relationship between sleep abnormalities and psychiatric illness include common neurobiological mechanisms for sleep regulation and mood. Sleep disturbance is part of the primary diagnostic criteria for several disorders. Medications used to treat psychiatric illnesses can have various effects on sleep, including exacerbation of insomnia and precipitation of primary sleep disorders. There may be an increased association between primary sleep disorders and psychiatric disorders. The possible causal relationships between sleep abnormalities and psychiatric symptomatology are not clearly understood. Do sleep abnormalities precipitate the onset of psychiatric disorders or are they simply an early sign of illness?


BACKGROUND
    Association between sleep disturbance and psychiatric illness

    Chronic sleep disturbance is highly correlated with psychiatric illness. In epidemiological surveys of the general adult population, at least one third of individuals with significant complaints of insomnia or hypersomnia showed evidence of primary psychiatric disorders, whereas rates of psychiatric illness were signifcantly lower in those without sleep complaints (Mellinger et al., 1985; Ford et al., 1989). Depression and anxiety disorders were the most common diagnoses. An assessment of the lifetime prevalence of sleep disturbance and psychiatric disorders in young adults also found greatly increased rates of psychiatric disorders in individuals with sleep complaints (70.7% for those with insomnia, 78.3% for those with hypersomnia and 88.9% for those with both insomnia and hypersomnia) in comparison to individuals with no sleep complaints (40.8%) (Walsh et al., 1994). Odds ratios for major depression were higher than for other illnesses. The association between insomnia and psychiatric illness may be even greater in clinical samples. Sleep disturbance, particularly insomnia, is reported by at least three-quarters of acutely ill psychiatric patients and persists in up to a third of patients even during periods of clinical remission (Sweetwood et al., 1980). A study of patients presenting to general medical clinics found that the symptoms of sleep disturbance and fatigue had the greatest positive predictive values (61% and 69%, respectively) for significant depressive symptoms (Gerber et al., 1992). Studies of diagnostic patterns in sleep disorders centers have found that the most common primary diagnosis for patients presenting with a complaint of insomnia is a psychiatric illness. In a multicenter study of patients evaluated by clinical interview and polysomnography, a diagnosis of insomnia related to psychiatric disorders was made in 35% of cases (Coleman et al., 1982). In a more recent study, psychiatric disorders were diagnosed in over 75% of insomnia and medical/psychiatric patients evaluated by clinical interview in sleep disorders centers (Buysse et al., 1994). There may also be an increased association between primary sleep disorders and psychiatric disorders. For example, patients with sleep apnea or narcolepsy appear to have elevated levels of anxiety, depression and substance abuse (Beutler et al., 1981; Guilleminault et al., 1978; Kales et al., 1982; Reynolds, III et al., 1984).



    Possible causal relationships between insomnia and psychiatric disorders

    It has historically been assumed that psychiatric disorders cause sleep disturbance. Possible explanations for the effects of psychiatric illnesses on sleep include the increased anxiety and arousal experienced by most psychiatric patients, abnormalities in circadian rhythms in some disorders, and neurobiological dysregulation in mood and behavioral systems which impact on sleep as well (Walsh et al., 1994). Sleep changes, however, may impact on psychiatric illnesses as well, and some epidemiological data support this contention. Subjects who reported insomnia at both an initial interview and a one-year follow-up interview were more likely to have developed a new major depression (odds ration 39.8) than were individuals whose insomnia had resolved by the second interview (odds ratio 1.6)(van den Burg et al., 1975). In a subsequent study using a similar two-wave longitudinal design, Breslau et al. (Breslau et al., 1996) found that a history of sleep disturbance in the baseline interview was associated with an increased risk for new onset of major depression, anxiety disorders, substance abuse disorders and nicotine dependence. The association appeared to be strongest between sleep disturbance and major depression, even when depression was defined on criterion symptoms other than sleep disturbance. The specific causal relationships between sleep loss and effects on psychiatric disorders have been most extensively studied in patients with mood disorders. Shifts into mania in bipolar patients are often preceded by periods of insomnia, and sleep deprivation has been shown to induce a manic state in susceptible individuals (Wehr et al., 1987; Wehr, 1991). Wehr has suggested that sleep deprivation may represent a final common pathway in the genesis of mania, and that sleep loss is both a precipitating and reinforcing factor for the manic state. New episodes of major depression are often preceded by periods of insomnia as well (Perlis et al., 1997). Although many patients with major depression believe their illness is the result of poor sleep, sleep deprivation has mood elevating effects in the majority of severely depressed patients, including those with significant insomnia (Leibenluft et al., 1992; Wu et al., 1990). Conversely, it appears that sleep may have depressogenic effects; even short amounts of recovery sleep can reverse the antidepressant effects of sleep deprivation, and patients with bipolar or seasonal depressions often sleep excessively. Specific sleep markers appear to have predictive value for the onset, longitudinal course and treatment response of mood disorders. Reduced REM sleep latency is not only associated with acute illness (Benca et al., 1992), but it persists in periods of clinical remission. Some studies have demonstrated that sleep abnormalities may be more severe in acute versus remitted phases (Kerkhofs et al., 1985; Knowles et al., 1986; Schulz et al., 1979). However, sleep abnormalities can persist for prolonged periods of time in otherwise asymptomatic individuals (Giles et al., 1989; Hauri et al., 1974; Puig-Antich et al., 1983; Rush et al., 1986). There is evidence to suggest that individuals with reduced REM latency but no prior history of depression may be at greater risk to develop depression than those with normal REM latency . For patients with depression and reduced REM sleep latencies, it has been shown that the REM sleep-suppressing effects of antidepressant medications were predictive of clinical efficacy (Gillin et al., 1978; Kupfer et al., 1976; Kupfer et al., 1981; Rush et al., 1989). Increased amounts of REM sleep rebound were also indicative of clinical response to the drug (Gillin et al., 1978). Furthermore, the efficacy of REM sleep deprivation in treating depression was correlated positively with both greater suppression of REM sleep early in the treatment as well as increased REM sleep rebound during recovery sleep (Vogel et al., 1980).



SUMMARY
    Psychiatric illnesses are strongly associated with sleep disturbances, including insomnia and hypersomnia. However, it is not clear whether psychiatric illnesses are caused by or produce sleep abnormalities, or if both are related to other primary factors. Most evidence for causal associations between sleep manipulations and psychiatric symptomatology relates to mood disorders. Sleep loss appears to have mood-elevating effects for bipolar patients in any mood state and for patients suffering with more severe episodes of major depression. However, both insomnia and hypersomnia are associated with an increased risk for the development of depression.


RECOMMENDATIONS
    Further research is needed to determine the functional relationships between sleep and psychiatric disorders. Specific questions include the following:

    1. What are the neural mechanisms for sleep changes in depression and other psychiatric illnesses?

    2. How do sleep manipulations lead to mood changes?

    3. Do sleep abnormalities lead to increased risk for psychiatric disorders, or do they simply indicate vulnerability?

    4. Do sleep patterns have predictive value in determining treatment response in psychiatric disorders? Do psychiatric disorders produce changes which are specific to sleep, or is sleep a window through which we can observe broader changes in EEG and/or functional organization of the brain?





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Ruth Benca, University of Wisconsin-Madison Madison, Wisconsin


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