Significant clinical overlap between depressive and anxiety symptoms is a frequent phenomenon. Differential diagnosis on clinical grounds alone is not easily accomplished. Sleep EEG findings from our center lend support to the view that the two disorders are distinct biologically. Our data further suggest that in younger individuals (<40 years) significant clinical symptomatic overlap of anxiety and depression is more likely to reflect anxiety neurosis as the primary diagnosis; depressive manifestations, often with atypical features such as over­eating, initial insomnia, and daytime somnolence, lethargy, or fatigue represent secondary phenomena. Finally, in older patients (>40 years), panic attacks and other signs of autonomic irregularity —once concurrent medical causes are ex­cluded—are more likely to represent genuine manifestations of primary depres­sive illness.

The subjects in this study (4) were consecutive referrals to our Sleep Disorders Center located in a private setting. All but one were outpatients. The group of anxious depressives (« = 22) consisted of various DSM-III (6) anxiety disorders: 11 with generalized anxiety disorder, 5 with full-blown panic disorder, and 3 with agoraphobia with panic attacks; in 1 patient the anxiety state was best defined as a simple phobia, and in 2 patients the additional diagnosis of obsessive-compulsive disorder could be given. Low grade, typically subsyn-dromal, fluctuating depression occurred in most subjects. However, anxiety symptoms were the dominant clinical core and typically preceded the onset of the depressive symptoms. In view of the chronicity of the illness in the anxious depressive group, we chose depressed subjects with comparable chronicity (n = 20). They consisted of individuals with early onset and long-standing, fluctuating subsyndromal de­pressive symptoms in the absence of a diagnosable nonaffective illness from the Washington University list (9) of validated psychiatric disorders; exception was made for substance use disorders, which can complicate the early course of primary mood disorders before full syndromal episodes occur. These patients conformed to what we have elsewhere (1) defined as a subaffective dysthymic disorder, i.e., a form of dysthymia that is a subsyndromal but chronic manifes­tation of major depressive illness and that is referred to as primary dysthymia in the latest DSM-III revision. The nonpsychiatric control group (« = 11) consisted of patients with medical illness and asymptomatic volunteers without evidence of major psychiatric dis­order by DSM-III criteria. All of them were in some physical discomfort due to their medical condition or to the various sleep monitoring montages in which they had volunteered to participate. Such a comparison group was necessary in order to determine whether sleep EEG findings in the depressive and dysthymic groups could be distinguished from those with nonspecific effects of mild to moderate stress. The routine procedure in our sleep disorders center (5) consists of at least 14 days free of psychoactive drugs (except for "stable" nicotine and caffeine intake); the Minnesota Multiphasic Personality Inventory (MMPI) and the Beck Depres­sion Inventory (BDI); formal psychiatric evaluation completed blind to sleep polygraphy; at least two consecutive nights of sleep polysomnographic study consisting of continuous EEG, horizontal electrooculogram (EOG), submental electromyogram (EMG), and electrocardiogram (EKG). Categorical data were analyzed by chi-square (with Yates’ correction when appropriate) and continuous data by ANOVA. In all three groups, the mean age of subjects was around 40, and sex ratio nearly even. Insomnia was a prominent clinical feature of the anxious patients, which differentiated them from the dysthymics (P < 0.05). The anxious patients had moderately elevated BDI scores (15 ± 10) indicating a level of subjective dysphoria comparable with that of the dysthymics (17 ± 8). This finding underscores the similarity of cross-sectional dysphoric complaints in those two groups and explains the difficulties in clinical differential diagnosis. Further, on four MMPI scales measuring dysphoric and somatic symptoms, the only significant difference between the anxious and dysthymic groups was higher mean psychasthenia scores in the latter (P < 0.02). Finally, dysthymics appeared to be globally somewhat more symptomatic than the anxious patients as reflected in modestly higher mean numbers of elevations exceeding 2 SD on the 10 MMPI psychopathology scales (P < 0.05). Compared with dysthymic and control subjects, the anxious group experienced significantly greater difficulty adapting to the sleep clinic environment on night 1. This was manifested by lower mean (±SD) sleep efficiency percentage in the anxious versus the dysthymic and control groups (P < 0.001), and a higher mean (+SD) number of awakenings in the anxious versus the dysthymic and control groups (P < 0.001). In addition, the anxious group had significantly longer (P < 0.02) mean (±SD) REM latency (128 ± 173 min) compared with the dysthymics (66 ± 23 min) but not the controls (108 ± 39 min). Mean REM% (±SD) showed a similar pattern with anxious patients comparable with controls but significantly lower (P < 0.02) than the dysthymics. In brief, compared with the anxious group, dysthymics and controls had less trouble in sleep continuity on the night of adaptation, but dysthymics could be distinguished from the other two groups on the basis of shorter REM latency and higher REM%. Table 1 summarizes significant night 2 differences. The sleep efficiency of the anxious group had improved to a level comparable to that of the other two groups, but they continued to experience higher degrees of arousal as measured by greater mean number of gross awakenings and stage shifts; dysthymics were no worse than nonpsychiatric controls on measures of sleep continuity. The major differences between the groups were in REM measures: dysthymics had significantly shorter REM latencies and higher REM% compared with the other two groups, which were indistinguishable. Thus, although group differences are less prominent on night 2, anxious and dysthymic subjects can still be differ­entiated on selected measures of sleep continuity and REM sleep. Comparing the variability of the three groups across nights demonstrated that anxious subjects experienced greater change (improvement) than the other two groups in sleep latency (P < 0.02), sleep efficiency (P < 0.001), and number of awakenings (P < 0.005). Overall, these findings testify to the greater adaptational difficulties of the anxious patients in sleep continuity. By contrast, REM measures appear relatively robust across nights in all groups. To summarize, despite overall comparable levels of dysphoria and chronicity, anxious depressive and dysthymic patients could be distinguished neurophysi-ologically. The performance of the sleep EEG in differentiating the two groups should be measured against the background of the failure of psychometric mea­sures to set them apart. Shortened REM latency appears to be the most robust difference. This difference has now been shown (8) to be accentuated with the cholinomimetic drug arecoline that reduces the latency in primary mood dis­orders but not in primary anxiety disorders. From a clinical standpoint, the increased number of awakenings, especially in the early part of the night, in the anxious group are significant in that they underline the patients’ tendency to achieve normal sleep patterns only in the last part of the night, hence the irri­tability, fatigue, and somnolence—the "neurasthenic" triad—so characteristic of anxious neurotics.

This study (2,3) compared masked depressives (n = 25) with classical major depressives (n = 20) and anxious depressives (n = 22) with comparable age and sex (Table 2). Masked depressives were affectively ill patients who were referred from primary care settings with autonomic manifestations of anxiety and who denied subjective depressive complaints. Such patients, who constitute a large segment of the psychiatrically ill population seen in general medical practice, may be considered "crocks," "hysterics," or "hypochondriacs." They usually are treated with benzodiazepines or other sedative-hypnotics on which they often become dependent. In our sample, which was free of psychoactive medication for 2 weeks prior to sleep study, lethargy, insomnia, fear of choking in sleep, chest pain, and impotence were the most common presenting complaints; except for subjective depression, they also met the Washington University (9) and DSM-III (6) criteria for major depression. Compared with major depressives diagnosed using both Washington University criteria (9) and DSM-III (6), masked depressives denied psychological manifes­tations of the depressive syndrome and showed low BDI and MMPI D (depres­sion) scores; furthermore, as judged by the number of elevated scales above 2 standard deviation, they were less likely to volunteer psychopathology on all the scales of the MMPI. When compared with patients who met the full criteria for hysterical neurotic, and sociopathic and anxiety disorders, masked depressives had shorter REM latencies similar to those of primary major depressives. Such findings suggest that some primary depressions with a protracted course occur in the absence of subjective depression; autonomic nervous system manifestations of anxiety or other somatic complaints are the major presenting complaints.

1. Akiskal, H. S. (1983): Am. J. Psychiatry, 140:11-20. 2. Akiskal, H. S. (1983): In: Affective Disorders Reassessed, edited by F. Ayd, I. J. Taylor, and B. J. Taylor, pp. 125-137. Ayd Medical Communications, Baltimore. 3. Akiskal, H. S. (1983): Psychiatric Developments, 1:123-160. 4. Akiskal, H. S. (1984): J. Affective Disord, 6:287-295. 5. Akiskal, H. S., Lemmi, H., Yerevanian, В ., King, D., and Belluomini, J. (1982): Psychiatry Res., 7:101-110. 6. American Psychiatric Association. (1980): Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. American Psychiatric Association, Washington, D.C. 7. Davidson, J. T. R., Miller, R. D., Turnbull, С D., and Sullivan, J. L. (1982): Arch. Gen. Psychiatry, 39:527-534. 8. Dube, S., Kumar, N., Ettedgui, E., Pohl, R., Jones, D., and Sitaram, N. (1985): Biol. Psychiatry, 20:408-418. 9. Feighner, J. P., Robins, E., Guze, S. G., Woodruff, R. A., Winokur, G., and Munoz, R. (1972): Arch. Gen. Psychiatry, 26:57-63. 10. Lloyd, G. E. R. editor (1983): Hippocratic Writings. Penguin Books, Hammondsworth, England. 11. Reynolds, С F„ Shaw, D. H., Newton, T. F., Coble, P. A., and Kupfer, D. J. (1983): Psychiatry Res., 9:81-89. 12. Roth, M., and Mountjoy, Q. (1982): In: Handbook of Affective Disorders, edited by E. S. Paykel, pp. 70-92. The Guilford Press, New York. 13. Sargent, W. (1961): Br. Med. J., 1:225-227. 14. Torgersen, S. (1983): Arch. Gen. Psychiatry, 40:1085-1089. 15. Uhde, T. W., Roy-Byrne, P., Gillin, J. C, Mendelson, W. G., Boulenger, J. P., Vittone, B. J., and Post, R. M. (1984): Psychiatry Res., 12:251-259. 16. VanValkenburg, C, Akiskal, H. S., Puzantian, V. R., and Rosenthal, T. L. (1984): J. Affective Disord., 6:67-82. 17. West, E. D., and Dally, P. J. (1959): Br. Med. J., 1:1491-1494.
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Sleep Disorders Center, Baptist Memorial Hospital and "Department of Psychiatry, University of Tennessee, Memphis, Tennessee, 38163
Patients with fear or depression of long standing are subject to melancholia. Hippocrates, Aphorisms V (10) A woman at Thasos became morose as the result of a justifiable grief, and . . . she suffered from insomnia, loss of appetite . . . she complained of fears and talked much; she showed despondency and . . . many intense and continuous pains. Hippocrates, Epidemics HI (10) (more…)

There exist a group of patients commonly seen in primary care as well as psychiatric settings that exhibit admixtures of depressive and anxiety symptoms that fluctuate over time on a subacute or chronic basis. They are variously referred to as anxious depressives, mixed anxiety depressives, and atypical depressives. A longitudinal perspective is necessary to determine the temporal relationship between the depressive and anxiety symptoms. When anxiety symptoms antedate depressive manifestations —and this is often the case in young individuals—then the likelihood is that this is a neurotic illness complicated by depression. Patients who have suffered from many years of generalized anxiety or full-blown panic attacks gradually get demoralized and disgusted with themselves; insomnia in the first half of the night leads to a tendency to feel fatigued and hypersomnolent in the morning, hence the origin of several of the symptoms that are considered to be atypical depressive manifestations. Even in the original British reports (13,17), these atypical depressive patients with neurasthenic symptoms were ba­sically considered anxiety neurotics. In these patients studied in our sleep lab­oratory, polysomnographic findings have failed to reveal REM sleep findings characteristic of primary depressive illness, and instead have shown features observed in anxiety disorders (i.e., multiple awakenings in the first half of the night). Hence our contention that a subgroup of atypical depressives is more appropriately described as atypical anxiety disorder, and would therefore benefit from monoamine oxidase inhibitors or alprazolam. Other depressives with atyp­ical features conform to the subaffective dysthymic pattern and are more likely to respond to noradrenergic tricyclics and lithium carbonate (1); these patients represent genuine forms of primary mood disorder and are unrelated to anxiety disorders. In other words, there seem to be at least two types of atypical depression (7), of which one with anxious depressive features is more accurately classified as an anxiety disorder. When anxiety symptoms occur in the setting of depressive manifestations — and this is often the case in older individuals—one must give preference to the diagnosis of a primary depressive illness. As emphasized in DSM-III (6), an anxiety disorder rarely, if ever, begins after the age of 40. Unfortunately, this fact is sometimes forgotten and manifestations indicative of autonomic nervous system hyperactivity are automatically ascribed to a neurotic illness. Indeed, once physical illness is excluded, the diagnosis of an anxiety state, rather than primary depressive illness, is initially entertained by many primary care physi­cians. What complicates differential diagnosis is the fact that some of these pa­tients completely deny the subjective psychological symptoms of mood disorder, e.g., depression, anhedonia, lowering of self-esteem, guilt, suicidal ideation, etc. Among the masked depressives studied in our sleep laboratory, about a dozen were middle aged or elderly patients (in their late 40s or older) who presented with such symptoms as sudden awakening with intense autonomic arousal and the fear of dying in their sleep. None of these patients had experienced panic attacks in their younger years or had premorbidly exhibited neurotic patterns. Elderly individuals with no psychiatric illness showed modest shortening of their REM latency. But even after taking this fact into consideration, the patients we studied with fear of dying in their sleep and other autonomic manifestations of anxiety had sleep EEG findings characteristic of primary depression. It would appear that the mere presence of anxiety attacks is not diagnostic of anxiety neurosis in that such attacks appearing for the first time after age 40 may represent affective equivalents. Melancholic patients presenting in this way are typically agitated and experience intense apprehension; they may even harbor delusions regarding calamities to themselves and their loved ones, which confirms the diagnosis. These agitated melancholias should be treated like other primary depressives. The use of benzodiazepines, if needed, should be purely on a symp­tomatic basis and limited to short periods of time to supplement standard an­tidepressant therapy.