A scale consists of a defined continuum or dimension along which judgments are placed. The scale may be a set of ordered categories with numbers attached corresponding increasing or decreasing amount of severity or other quantitative characteristics of the phenomena being observed. The form of a psychological scale is dependent on particular psychometric techniques; the content, however, is dependent on the underlying psychological theory as noted by Hamilton (6). Psychiatric scales are special kinds of psycho­logical scales. They derive their form from the science of psychological scales in general (about which there is a vast literature) and their content from underlying theories and notions concerning the nature of psychiatric illness thought relevant by various schools of psychiatry. Characteristics of Clinical Scales in Affective Disorders For practical purposes clinical scales in psychiatry have been divided by Garside (4) into four main types, each with distinct characteristics. The first type is the assessment or descriptive scale that can be used to assess the degree of psychiatric illness such as depression. An example of this type of scale is the Hamilton Depression Scale (HDS) (5). The second is discriminatory rather than descriptive, and may be useful in arriving at a psychiatric diagnosis; an example of this scale is the Newcastle Diagnostic Index (2). The essential feature of a descriptive scale is that individual items should correlate more highly among themselves and give rise to a general factor indicating that it is meaningful to describe patients along such a dimension, i.e., convergent validity. In diagnostic scales, it is essential that the items produce separate correlational groups, i.e., discriminant validity. While there appears to be some general agreement on empirical findings with the use of descriptive scales (12), there has been little general agreement on findings on diagnostic scales in depression, for instance. Descriptive scales have also been referred to as quantitative scales to distinguish them from qualitative ones, e.g., discriminatory or diagnostic scales (1). The other types of scales are predictive, in the sense of predicting the course and outcome of particular psy­chiatric conditions, as in Kerr et al. (8), Paykel (11), and Carney et al. (2). These latter scales will not be discussed further in any detail. There are a number of commonly used and established descriptive scales for measuring anxiety and depression (Table 1). The main uncertainty in their use centers on the question of validity. There are uncomfortably high correlations between any of the scales listed measuring depression and those designated to measure anxiety (10). For instance, the Hamilton Depression and Hamilton Anxiety Scales show intercorrelations of around 0.5 to 0.6 in the literature. This could suggest that clinical anxiety and depression are highly correlated. However, impure scales could magnify this relationship, and most of our present scales fail to distinguish anxiety from depression adequately enough. What if, for instance, the HDS was not a sufficiently pure measure of the illness termed depression. After all, it was designed on a logical empirical basis by Max Hamilton, although he did go on to examine its psychometric properties. What if the margin of error in accuracy was, say 30% or even 50%, where would that leave interpretations of amine levels or pharmacological treatment indices, when the HDS is the critical variable?
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The type of treatment of the anxious-depression of the aged patient, on the basis of what is reported above, should consider three main variables: the role of anxiety, the primarity or endogenicity of the depression, and the coexistence of somatic disorders. Anxiety, insomnia, and somatizations justify the onset of a secondary depres­sion and may play a preeminent role in the depressive picture. In this instance, anxiety should be treated with anxiolytic agents, first of all of benzodiazepine type, or with low-dose neuroleptics, or as a second choice with beta-adrenergic blockers or valproic acid amide. The choice of one of these agents could be motivated as follows: the use of benzodiazepines appears to be justified especially by the lack of important organic problems (vascular or metabolic brain disorders). It is known that benzodiazepines (BD2) could cause paradoxical effects, such as psychomotor agitation or confusional states, especially in subjects with a marked metabolic impairment in CNS. In other terms, the more impaired the cerebral functions, the easier the onset of paradoxical effects or side effects (confusional states). At any rate, it is necessary to prefer BDZ without active metabolites and with a short or ultra-short half-life (oxazepam, triazolam) without risks of ac cumulation owing to longer half-lives since the marked reduction of liver met­abolic capacity. The new BDZ, so-called antidepressant benzodiazepines such as alprazolam, adinazolam, zometapine (this latter is still in the stage of phase II study) are rather interesting, since they act on the noradrenergic system and exert an an­tidepressant as well as an anxiolytic action. The limit to the use of these agents is that they can activate, in some cases, the anxious somatizations and, therefore, are contraindicated if the degree of somatization is particularly remarkable. Low-dose neuroleptics, such as trifluo­perazine and thioridazine, have no contraindications; but it must be stressed that they could worsen the depression, if it is not secondary to the anxious phenomena, but is elusive, creeping, and masked in its severity (depressive "iceberg").
Beta-adrenergic blockers are particularly indicated in the course of somati­zations, especially at heart level. The limit to their use is that they are of course hypotensive and, therefore, must be used in low doses and, like neuroleptics, could worsen depression. Concerning the use of valproic acid amide, it is widely used in subjects in which treatment with the above mentioned agents is problematic, and, in any rate, it could be combined with one of them, since valproic acid is a metabolic inhibitor and will tend to raise the blood levels of the combined drugs, with the obvious result that the side effects will also increase. In the course of anxiolytic therapy, it is possible that the patient has no more anxiety or somatizations, but the depressive features not only do not disappear, but could even become more evident and severe. This could suggest hidden endogenous depressive elements, probably worsened by the use of a neuroleptic Read the rest of this entry »

Baseline profiles were derived from the HSCL-90 self-rating scale, and the SUMMY variables for this sample were first compared with the same baseline measures derived from the first 80 Pisa Center subjects enrolled in the Worldwide Upjohn Phase II Study for Panic Disorder (9). The Upjohn study patients were selected utilizing stricter criteria in two respects, compared with the CLO-IMI study; the Upjohn study required at least one panic attack each week during the month before evaluation, whereas the CLO-IMI study required panic attacks during the past month without specifying disorder, or other anxiety disorder, whereas the CLO-IMI study did not. Even though the 152 subjects participating in the IMI or CLO treatments were selected according to broader, less restrictive criteria, they did not differ significantly from the Upjohn sample in any of the major SUMMY variables (Table 2). Contrary to expectation, the depressive mood item from the HDS was not significantly higher in the more leniently selected open study sample. Obviously, owing to selection criteria, the Upjohn study patients would be ex­pected to have more spontaneous and situational panic attacks, but even these differences were small and nonsignificant. The variance in monthly number of situational panic attacks was higher in the Upjohn sample (p < 0.05), indicating
that relatively few cases accounted for the mean difference of two attacks per month between the two samples. The open study patients had slightly higher ratings on phobic avoidance, anticipatory and baseline anxiety, and impaired social adjustment (i.e., greater disability). A comparative analysis of the HSCL-90 factors also confirmed nearly super-imposable psychopathological profiles for the two groups (Table 2). The open study sample was slightly to somewhat higher in mean scores on all the psycho-pathology factors, but only the obsessive-compulsive factor mean was significantly higher, whereas the depression factor was nearly so. The actual rank ordering of the 9 HSCL factors by their weighted mean item scores was practically identical for the two samples. These baseline comparisons of the two study samples suggest a particular stability of the panic-phobic diagnostic categories. Although the operational cri­teria for the disorders were less strictly followed in the open trial, the typical panic-phobic syndromes are clearly present in that sample, and the overall profiles of psychopathology are remarkably similar. In the CLO-IMI study, the two treatment groups were comparable in the proportion of the three DSM-III-R diagnoses and in age, sex, and age at onset. These characteristics were also not related to dropout rates. The attrition rate to date has included 31 IMI and 29 CLO patients. None of these cases returned after the first visit and then were lost to follow-up. The attrition rate did not differ for the two groups, but patients lost from the IMI group had significantly more situational panic attacks per month than those who discontinued CLO treatment (Table 3). Dropouts from the two treatments did not differ significantly in the other syndrome features shown in Tables 3 and 4. At present 33 patients are in progress in the study but have completed less than 10 weeks of treatment. The 33 IMI and 26 CLO cases who have completed the 10th week did not differ significantly at baseline in any of the major features shown in Table 3. Read the rest of this entry »

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.

Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06510
The occurrence of anxiety symptoms with episodes of major depression is veil documented (2,8-11,16). When individuals with either an anxiety disorder or major depression are followed over time, a particularly strong association has been observed between panic anxiety and depression. Dealy et al. (8) compared patients who had anxiety neurosis alone with patients who had anxiety neurosis with major depression. They found a significantly elevated rate of panic attacks among patients with depression. Other studies have suggested that when the two disorders co-occur in the same individual, they may be temporally independent. Raskin et al. (17) reported that 14 of 17 patients with panic disorder had expe­rienced major depression that did not coincide with an episode of panic disorder. Bowen and Kohout (1) found that 91% of patients with agoraphobia and panic attacks had had an episode of major depression that did not coincide with episodes of panic, whereas Munjack and Moss (14) found that 41% of agoraphobic patients with panic attacks had had previous episodes of depression. Results from other studies have also suggested an association between panic disorder and depression. However, none of these studies specifically addressed whether the two disorders occurred together or separately. Cloninger et al. (4) noted that 75% of patients who experienced panic attacks later developed depres­sion and Crowe et al. (6) found that 13 of 41 patients with panic disorder had chronologically secondary depression. In a follow-up study of 29 patients with "cardiac phobia," Nutzinger and Zapotoczky (16) found that 82.8% showed depression in addition to suffering from anxiety symptoms. While it is clear that the onset of depression came after the onset of anxiety in these studies, the investigators did not report whether the episodes of depression occurred inde­pendently of the episodes of panic disorder experienced by the patients. In examining patients with major depression, Leckman et al. (12) found that 81 of 133 patients had anxiety disorders in addition to being depressed. Twenty­two of the 81 individuals with both anxiety and depression had panic disorder. of the total 133 depressed subjects, 16.5% experienced panic attacks with suf ficient frequency and severity to satisfy criteria for a diagnosis of probable or definite panic disorder. This frequency is higher than expected by chance alone. These results, taken with the data from studies of panic disorder patients, suggest that panic disorder (PD) and major depressive disorder (MDD) may share some etiological factors. Treatment studies have also provided data that support the hypothesis of a potential relationship between PD and MDD. It is well known that tricyclic antidepressants and monoamine oxidase inhibitors are effective in the treatment of MDD (7). Evidence from controlled studies indicates that these agents also are effective in the reduction of the frequency of panic attacks (3). This antipanic effect appears to be independent of clinical manifestations of depression (18,22) suggesting that there may be some common underlying etiological factors for both panic and major depressive disorders. Although results from the above studies imply that PD and MDD are strongly associated and may have common factors involved in their etiology, additional data are needed to examine more carefully the relationship between the two illnesses. Since both disorders have been shown to be familial, family data can be quite useful in elucidating whether they share etiological factors. If PD and MDD are etiologically related, then increased rates of one disorder should be observed in the relatives of patients with the other illness. Family data have given apparently contradictory results. Several studies (1,12,14,19) have suggested that there is a familial relationship between PD and MDD since an increased rate of depression was observed among the relatives of probands with either MDD and PD (MDD + PD) or with PD alone. However, other studies (6,15) did not find an increased rate of primary depression in the relatives of probands with PD or agoraphobia with panic attacks (Ag/PD). The discrepancy between these family study results may be accounted for by meth­odological differences (5,13). The purpose of the study reported here was to reexamine the reports of Leckman et al. (12), Crowe et al. (6), and Noyes et al. (15) to determine if methodological differences could account for the apparent discrepant findings. Methodological differences between the studies focused on the procedures used in assigning diagnoses. In the Crowe et al. and Noyes et al. studies, DSM- III convention was used in that a diagnosis of a specific psychiatric condition was precluded when it could have been secondary to another mental disorder. For example, a diagnosis of primary major depression would not have been made if it occurred after the onset of panic disorder. Thus, the morbid risk figures reported in these two studies reflect the rates of chronologically primary disorders. These rates, in effect, represent the frequency of ill individuals among the relatives since no one would be included more than once. On the other hand, Leckman and co-workers did not use the primary/secondary distinction in re­porting diagnoses. If an individual had sufficient symptoms to meet DSM- Ш criteria for a specific diagnosis, that diagnosis was assigned and reported. An individual could, and often did, receive several diagnoses. Therefore, the rates reported by Leckman et al. were rates of diagnoses and not rates of ill individuals, дп individual was included in the computation of rates as many times as that person received a diagnosis. Because of this difference in how rates of illness were reported, it is difficult to compare the results of the studies.

The authors would like to acknowledge the contribution of Drs. V. K. Sharma, P. Saunders, C. Sullivan, С McWilliam, L. M. Voruganti, and S. V. Manohar, who undertook the follow-up interviewing, and Dr. N. Wood, Miss M. Heary, Mrs. J. Silcock, Miss C. Hensey, Mrs. J. Wood, and Mrs. R. Searle, who undertook the interviewing of the initial sample. Our thanks are also due to Mr. M. Kayodi for his work on the computer and to Mrs. B. Ackerley for her skill in organizing the interviewing. This research was supported by grants from the Wellcome Trust and the Mersey Regional Health Authority, United Kingdom.
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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.

The total scores of the scales, and individual clinical, personality, and bio­graphical items were subjected to Principal Component Analysis. A series of sequential analyses indicated the stability of the clusters derived. Figure 1 illus­trates a typical outcome of this analysis, with symptoms and personality scores included. It can be seen that the upper right-hand quadrant contains a cluster of items that are consistent with the entity depression; similarly in the upper left-hand quadrant is a cluster consistent with the term anxiety. These data were reanalyzed a number of times, leaving out a variety of items on each occasion and were also analyzed separately for sex. No matter which items were included or excluded, the basic patterns established remained invariant.
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Brain 5-hydroxytryptamine (5HT) system has been implicated in the processes associated with the response to punishment and the suppression of behavior, as in conflict situations (29). The selective neurotoxin lesions of the 5HT forebrain pathways reverse the suppressive effects of punishment, as do anxiolytic drugs, supporting the view that 5HT may play a role in conflict behavior and in the biology of anxiety disorders. It has been reported that release of behavioral suppression following intraraphe chlordiazepoxide was abolished by prior 5,7-dihydroxytryptamine infusion in this nucleus (27). On the other hand, evidence against the involvement of se­rotonergic neurons in the antipunishment activity of diazepam in the rat has been also demonstrated (28). However, it is known that different classes of anxiolytics, including benzodi­azepines, cause marked inhibition of dorsal raphe neuronal firing (7). Consistent with this finding is the fact that benzodiazepines significantly reduce 5HT turn­over in the central neurons system (32). The role of 5HT neurons in the effects of anxiolytic drugs has recently become of interest in studying a novel nonben-zodiazepine agent, buspirone (8) (Table 1). Unlike diazepam, buspirone has no effect on the benzodiazepine-GABA receptor complex. It is inactive at benzo
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