79

Journal of Affective Disorders, 20 (1990) 79-85 Elsevier

JAD 00743

Concordance

of symptoms

in recurrent

depressive

Michael A. Young, Louis F. Fogg, William A. Scheftner

episodes

and Jan A. Fawcett

Department of Psychiatry, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL 60612, U.S.A. (Received 27 March 1990) (Accepted 14 May 1990)

Summary The presence or absence of 12 depressive symptoms was examined in 93 bipolar and 108 unipolar patients who had two discrete episodes of major depression over a 5-year period. For each symptom the concordance of its presence or absence across episodes was low. The agreement observed was largely that to be expected by chance. A substantial amount of concordance was obtained if differences in episode intensity (propensity to have symptoms) were taken into account. This suggests that although there may be factors related to depression which remain stable across episodes, symptom presentation is moderated by other factors, such as intensity, which vary from episode to episode.

Key words: Recurrent depression; Course; Symptoms; Concordance

Introduction The course of depressive disorder tends to consist of recurring episodes. Each episode may meet diagnostic criteria for major depression based on the composite of symptoms exhibited. However, the specific symptoms in different episodes can vary. The similarity of symptomatology within individuals from episode to episode has not been studied. This kind of information could shed light on the nature of the pathology of recurrent depression. For example, Young et al. (1987) found that the Research Diagnostic Criteria (RDC;

Address for correspondence: Dr. M.A. Young, Department of Psychiatry, Rush-Presbyterian-St. Luke’s Medical Center, 1725 W. Harrison Street, Suite 915, Chicago, IL 60612, U.S.A. 0165-0327/90/$03.50

0 1990 Elsevier Science Publishers

Spitzer et al., 1978) endogenous subtype was unstable within patients across episodes. This suggests that the endogenous subtype does not represent a trait characteristic of major depressive disorder. Similarly, Winokur et al. (1985) found psychotic symptoms to be unstable in multiple episodes of affective disorder. We will use the term “concordance” to indicate systematic agreement in the presence or the absence of a symptom in two episodes of depression. One might hypothesize that there are relatively stable pathological processes which result in depressive symptoms and that consequently symptoms will be relatively concordant across episodes. Informal communication suggests that a number of clinicians believe that their patients do exhibit similar symptoms in recurrent episodes. Concordance would be expected regardless of the biologi-

B.V. (Biomedical

Division)

80

cal, psychological or social sources of the pathology as long as the processes which lead to symptoms remain constant. This theory does not require all individuals to have the same pathological processes, only that the processes remain stable over time within each individual. Such a theory predicting symptom concordance across episodes could be incorrect for at least two reasons. First, the basic pathological processes leading to symptoms could differ from episode to episode even within a single individual. For example, biological or psychological treatments could alter these processes. Likewise, levels of stressful events or social supports could change. Second, while certain pathological processes might remain stable within the individual, symptoms might be mediated by other factors which differ over time. For example, a constant basic pathology may lead to the onset of episodes but the particular symptoms exhibited may be determined by physiological, psychological and social factors which are variable. As a result, concordance across episodes would exist at some level of pathology but not at the level of symptoms. One additional factor which could affect the concordance of symptoms is the severity of the episodes being compared. For example, a symptom might occur in a more severe episode but not appear in a less severe episode. Severity differences could result from natural course or treatment intervention. However, what exactly do we mean by “severity”? Severity is a complex term which may include the magnitude of experienced distress, the type of symptoms (e.g., delusions) and the degree of impairment (e.g., social withdrawal, suicide). Here, as a construct to explain the presence or absence of symptoms, we mean only that some episodes tend to have more symptoms while other episodes tend to have fewer symptoms. Thus, episodes may be characterized on a dimension of their propensity to have a greater or lesser number of symptoms. We will use the term intensity to correspond to this more specific aspect of severity. Thus, if one episode has a low intensity and another a high intensity, one might expect that the concordance of symptoms in these episodes would be less than if the episodes were of equal intensity. Regardless of the theoretical position adopted,

one would not expect symptoms to exhibit either absolute concordance or complete randomness. The purpose of the current study was to assess the magnitude of concordance and evaluate what light this sheds on the nature of depressive psychopathology. Two models were evaluated. The first model implemented the usual adjustment for the degree of concordance to be expected due to chance given the base rate of the symptom in the sample. This is an important step since the clinician’s observation is of an individual patient while the influence of chance can only be assessed on a group basis. For example, if 70% of subjects exhibit a symptom in each episode, 49% of subjects will have the symptom in both episodes by chance overlap alone. The second model modified the first by assuming that concordance of symptoms also depends on the similarity of the intensities of the episodes. Methods Subjects were the 201 patients from the NIMH Collaborative Study of the Psychobiology of Depression who had two episodes of depression over a 5-year observation period (21.0% of the original sample). The goals and design of the overall project have been described elsewhere (Katz and Klerman, 1979). The project was conducted at hospitals associated with five academic centers: Rush-Presbyterian-St. Luke’s Medical Center in Chicago, Harvard Medical School in Boston, The University of Iowa School of Medicine in Iowa City, New York State Psychiatric Institute in New York City, and Washington University School of Medicine in St. Louis. Patients were seeking psychiatric treatment through the customary referral mechanisms of the institutions. They were required to be at leas{ 17 years old, Caucasian, fluent in English, above 70 in IQ, without evidence of organic brain syndrome, and knowledgeable of their biological parents. All subjects were evaluated with the Schedule for Affective Disorders and Schizophrenia (SADS; Endicott and Spitzer, 1978) and met RDC criteria for a major affective disorder. Following intake, subjects were interviewed every 6 months for 5 years using the Longitudinal Interval Follow-up Evaluation (LIFE; Keller et al., 1987). Overall

81

severity was assessed using the Global Assessment Scale (GAS; Endicott et al., 1981). Data documented the offset of the intake episode and the onset and offset of subsequent episodes according to the RDC. At least 8 weeks of return to premorbid status was required for an episode to be concluded and data collection was not considered completed until the subsequent interview. For each episode, the presence or absence of the 18 RDC symptom items in the criteria for major depression, endogenous subtype, agitated subtype and retarded subtype were scored. Twelve non-overlapping symptoms were selected for study *: decreased appetite, fatigue, pervasive loss of interest or pleasure, mood worse in the morning, psychomotor retardation, psychomotor agitation, middle or terminal insomnia, recurrent thoughts of death or suicide, distinct quality of mood, lack of reactivity of mood, feelings of guilt, difficulty concentrating or indecision. Each of the 201 subjects recovered from their intake episode and had at least two subsequent episodes of major depression during the 5-year follow-up. If a subject had more than two subsequent episodes, the first two were used. Intake episodes were excluded because they differed from subsequent episodes in at least two ways. First, the assessment instrument (SADS) varied somewhat from that employed in the follow-up (LIFE). Second, intake episodes all included help seeking at major academic medical centers; all subsequent episodes were assessed regardless of treatment. Based on all information at the end of the 5-year follow-up 93 subjects had a bipolar disorder and 108 had a recurrent unipolar disorder.

* Three items appear identically twice. Psychomotor agitation and psychomotor retardation diagnostic subtypes were selected rather than the single composite psychomotor item of the major depression criteria. Pervasive loss of interest or pleasure was selected over its counterpart without the pervasive qualifier; “middle or terminal” insomnia was selected over “increased or decreased sleep”; and “decreased appetite” was selected over “weight loss” and “increased or decreased appetite or weight”. Items were avoided which were exhibited by nearly all subjects since these would be less informative.

These two groups were analyzed separately. Of the bipolar subjects, 64 were female and 29 were male. Their mean (SD) age was 37.8 (13.8) years. The mean (SD) time between the onsets of the two episodes was 67.0 (46.5) weeks. Of the unipolar subjects, 73 were female and 35 were male. Their mean (SD) age was 37.1 (14.4) years. The mean (SD) time between the onsets of the two episodes was 69.6 (44.5) weeks. Statistical analyses Concordance in symptom occurrence was assessed using Cohen’s kappa (Cohen, 1960) which adjusts for the magnitude of agreement expected by chance. A second goal of the analyses was to adjust the amount of concordance for the differences in intensities of the episodes. Constructing such an intensity variable corresponds to the statistical model of the item response theory of Rasch (1960; Gibbons et al., 1985). Widely used in education research, in the present application the Rasch model can be stated as: the probability of a particular symptom being present in a given episode is a function of (1) the intensity of the particular episode and (2) the “difficulty” of the particular symptom (i.e., how uncommon it is). It is assumed that the greater the intensity of the episode the greater the probability of its occurring in any given episode and that the symptoms form a hierarchy of difficulty. Note that the model is probabilistic rather than deterministic, so that it does not postulate a completely fixed sequence of symptom occurrence. The Rasch model was estimated using the Multilog computer program (Thissen, 1988). **

** Models for the two episodes were estimated separately for unipolar and bipolar subjects. Fit statistics for each subject and each symptom indicated a satisfactory fit (Wright and Stone, 1979). Since, for each episode, the correlation of the estimated intensity scores from the Rasch model and the total number of symptoms was 0.99 (not an uncommon occurrence, Lewine et al., 1983), for convenience we used the total number of symptoms present as the estimate of the intensity score. More details of these analyses are available from the authors. They are not presented here because the Rasch analysis was used to construct a plausible intensity variable, not as a study in itself.

82

Results

scores are equal for the two episodes. This is because the probability of each symptom being present will be equal in the two episodes. Second, if the intensity scores are unequal, symptoms will be relatively unlikely to occur in the lower intensity episode only. Third, the greater the difference in intensity scores, the lower the concordance in symptoms should be. By applying a Rasch model, we estimated an intensity score for each episode. We then reevaluated symptom concordance adjusting on a subject-by-subject basis for the intensity of each episode. Our data were congruent with these predictions. Twenty-two subjects had equal intensity scores in the two episodes. The kappas for these subjects (Table 3) were substantially higher than those originally observed, varying from 0.377 to 1.00 (median, 0.620). Seventy-one subjects had different intensity scores in the two episodes. Over the 12 symptoms, between only one and eight subjects (median, 4) had a symptom present in the low-intensity episode only. Of 381 subject-symptoms present during low-intensity episodes, 53 (13.9%) were absent in the high-intensity episode and could be considered cases of discordance. Finally, subjects were grouped by the absolute value of the difference in intensity scores of the two episodes. Although the results were not com-

Bipolar patients We first examined the general equivalence of the first and second episodes. The two episodes were very similar in frequency of each symptom, the total number of symptoms present and the overall severity as measured by the GAS (Table 1); none of the differences were statistically significant. Thus, any discordance in symptom picture cannot be attributed to group differences between first and second episodes. Given the overall equivalence of the episodes, were symptoms consistently present or absent on a subject-by-subject basis? The chance-corrected magnitudes of concordance are shown in Table 2. Kappas for the 12 symptoms were in the low to moderate range, varying from 0.066 to 0.572 (median, 0.356). What could account for the relatively low magnitude of concordance observed? One possibility is that for any particular individual the two episodes differed in intensity. This could occur even if the intensities of the episodes in the sample as a whole were similar. If this explanation of the original findings is correct three things should be observed. First, concordance in symptoms should be substantially greater for subjects whose intensity

TABLE

1

FREQUENCIES

OF SYMPTOMS Bipolars Episode

Unipolars I

Episode

II

Episode

I

Episode

II

Decreased appetite Fatigue Loss of interest/pleasure Worse in morning Retardation Middle/Terminal insomnia Suicidal Distinct mood quality Non-reactivity Agitation Guilt Concentration/Indecision

60.2 92.5 60.2 30.1 41.9 58.1 68.8 66.1 58.1 17.2 64.5 94.6

61.3 92.5 53.8 33.3 35.5 57.0 68.8 64.5 60.2 16.1 68.8 89.2

63.9 87.0 43.5 22.2 23.1 52.8 58.3 69.4 44.4 15.7 62.0 87.0

52.8 * 96.3 * 39.8 25.0 25.9 56.5 61.1 63.0 50.0 13.9 71.3 87.0

Mean (SD) N Sx Mean (SD) GAS

7.1 (1.9) 41.0 (11.3)

7.0 (2.0) 40.9 (11.4)

6.3 (1.9) 45.5 (9.2)

6.4 (2.0) 45.5 (9.6)

* P -c 0.05.

83 TABLE

2

MEASURES

OF CONCORDANCE:

BIPOLAR

SUBJECTS

Concordance

Decreased appetite Fatigue Loss of interest/pleasure Worse in morning Retardation Middle/Terminal insomnia Suicidal Distinct mood quality Non-reactivity Agitation Guilt Concentration/Indecision

Revised

f%Exp.

I Obs.

K

52.3 86.1 50.8 56.6 52.3 51.1 57.1 54.8 51.6 72.2 55.5 85.0

79.6 93.5 69.9 73.1 69.9 68.8 72.0 67.7 63.4 77.4 63.4 86.0

0.572 0.537 0.388 0.380 0.368 0.362 0.349 0.286 0.244 0.187 0.179 0.066

a Kappas for 22 subjects with equal intensity socres in the two episodes. ’ Number of subjects with unequal intensity socres (n = 71) who have symptom

pletely uniform, the degree of agreement generally decreased as the difference in intensity between episodes increased. It also is noteworthy that, while the mean intensity was nearly identical in the two episodes, the correlation of intensities across episodes was only a moderate 0.40. The correlation of intensity and global severity measured by the GAS was low to moderate (episode one, -0.244; episode two, -0.398).

TABLE

present

Ka

Low-intensity episodes only b

0.673 1.00 0.723 0.703 0.455 0.377 0.545 0.596 0.585 1 .oo 0.560 0.645

3 1 6 5 7 4 8 4 5 4 3 3

in the low-intensity

episode

only.

Unipolar patients The pattern of results for unipolar patients was very similar to that for bipolar patients, with kappa coefficients uniformly somewhat lower. The two episodes were generally equivalent (Table 1) with no significant differences in number of symptoms, GAS score or frequency of 10 of the 12 symptoms. Fatigue was significantly more frequent in the second episode (96.3% vs. 87.0%) and

3

MEASURES

OF CONCORDANCE:

UNIPOLAR

SUBJECTS

Concordance

Decreased appetite Fatigue Loss of interest/pleasure Worse in morning Retardation Middle/Terminal insomnia Suicidal Distinct mood quality Non-reactivity Agitation Guilt Concentration/Indecision

% Exp.

% Obs.

K

50.8 84.3 51.3 63.9 62.9 50.4 51.9 55.0 50.0 74.7 55.1 77.4

66.7 85.2 66.7 80.6 69.6 64.8 63.9 63.9 61.1 79.6 70.4 77.8

0.323 0.057 0.315 0.462 0.176 0.291 0.250 0.197 0.222 0.193 0.340 0.015

i Kappas for 18 subjects with equal intensity scores in the two episodes. Number of subjects with unequal intensity scores (n = 90) who have symptom

present

Revised lea

Low-intensity episodes only b

0.289 0.455 1 .oo 0.557 0.368 0.640 0.400 0.556 0.658 1.00 0.491 0.341

13 4 6 4 7 6 5 13 2 4 3 4

in the low-intensity

episode

only.

84

decreased appetite was more frequent in the first episode (63.9% vs. 52.8%). Kappas for the 12 symptoms were in the low to moderate range, varying from 0.015 to 0.462 (median, 0.270) (Table 3). Eighteen subjects had equal intensity scores in the two episodes. The kappas for these subjects (Table 3) were higher than originally observed, varying from 0.289 to 1.00 (median, 0.524). Seventy-one subjects had different intensity scores in the two episodes. Over the 12 symptoms, between two and 13 subjects (median, 4.5) had a symptom present in the low-intensity episode only. Of 473 subject-symptoms present during low-intensity episodes, 73 (15.4%) were absent in the high-intensity episode and could be considered cases of discordance. Finally, subjects were grouped by the absolute value of the difference in intensity scores of the two episodes. As with the bipolar subjects, the degree of agreement generally decreased as the difference in intensity between episodes increased. Also as before, while the mean intensity was nearly identical in the two episodes, the correlation of intensities across episodes was only a moderate 0.35. Intensity correlated moderately with global severity measured by the GAS (episode one, - 0.404; episode two, - 0.455). Discussion Is there concordance of symptoms across episodes of depression? The answer depends on what is meant by concordance. If you mean that from one episode to another the symptoms systematically tend to be the same, the findings here give an answer of “no”. The magnitude of concordance was low for both unipolar and bipolar subjects. In general, concordance was somewhat lower for unipolar than bipolar, perhaps not surprisingly since unipolars are a more heterogeneous group. It is possible that some syndrome of symptoms would show concordance while individual symptoms did not, although Young et al. (1987) did not find this to be true for the RDC endogenous subtype in essentially the same subjects studied here. It is important to note the impact on these results of adjusting for chance. Over the 12 symptoms studied, 63-93% of subjects had the symptom either present or absent in both episodes.

However, the majority of this agreement was to be expected by chance overlap alone. Thus, an informal clinical impression of concordance can be misleading because it does not adjust for how likely a symptom is to occur in any given episode (i.e., base rates). An individual patient may present with the same symptom in two episodes. But whether this can be attributed to some systematic concordance is a question that cannot be answered on a single case basis, One methodological factor to consider in interpreting these results is the inherent reliability of the measures. Concordance cannot exceed the expected repeatability of a single symptom assessment itself. The reliability of the instruments as used in this study has been reported to be good (Andreasen et al., 1981). Although limitations in reliability could have attenuated the kappas to some extent, it is not likely to account completely for the finding of low concordance. In addition, while (1) most subjects were rated by the same rater in both episodes, (2) raters were aware of clinical data from previous episodes and (3) the two episodes were relatively close in time, these factors would tend to increase concordance and thus the low kappas obtained would be an overestimate of the true magnitude of concordance, If by concordance we mean that symptoms tend to be the same in episodes of equal intensity, then findings here answer “yes”. After adjusting for differences in episode intensity there were substantial levels of concordance. Note that these higher kappa values were not a function of the level of intensity but of the similarity in intensity levels. This is true for two reasons. First, the intensity adjustment was based on differences in intensity. Second, kappa itself takes into account the base rates of symptoms and how these affect the amount of concordance/discordance possible. These results represent a substantial amount of structure in psychopathology, but not a simple structure or one that is easily applied clinically. Thus, we cannot say that if a patient had a symptom in one episode he is likely to have it in another episode. We can say that if the intensity of two episodes is similar then the specific symptoms are likely to be similar. In addition, if a symptom is present in a less intense episode it is unlikely to be absent in a more intense episode.

85

One might infer that two episodes differ in intensity because the more intense episode developed further and additional symptoms appeared. However, while this is possible, our data consisted only of the symptoms exhibited at any time during the episode and contain no information about their order in time. How do our findings relate to the theoretical perspectives presented originally? Because unadjusted concordance was low, the view that symptoms are the direct result of an underlying factor which remains stable across episodes is not supported. This suggests that while there may be underlying stable factors which are causally related to symptom occurrence, they are moderated by other factors which vary over time. Episode intensity appears to be one such factor: both specific symptoms and intensity vary across episodes, but when intensity is held constant specific symptoms exhibit substantial concordance. Interestingly, intensity functioned identically in both unipolars and bipolars. The implications of the concept of intensity are not clear. Intensity may be related to what is commonly referred to as severity. However, severity is a complex term and the correlations of severity and intensity were only low to moderate. In this study intensity was defined as the overall tendency for symptoms to occur in the episode; it did not include the severity of the symptoms present. It is important to note that individuals’ episodes differed not only in the severity of the symptoms but in the specific symptoms experienced. Does intensity represent a marker for some more basic pathological process or for the final common pathway of a variety of factors related to symptom manifestation? How to define and measure intensity and how it relates to other variables are questions requiring further research. Also, a substantial amount of discordance in symptoms remained even after adjusting for intensity. Some of this is to be expected based on the probabilistic

model relating intensity and symptom occurrence. Other portions are likely due to other determinants of depressive symptoms which vary over time. References Andreasen, N.C., Grove, W.M., Shapiro, R.W., Keller, M.B., Hirschfeld, R.M.A. and McDonald-Scott, P. (1981) Reliability of lifetime diagnosis. Arch. Gen. Psychiatry 38, 400-405. Cohen, J. (1960) A coefficient of agreement for nominal tables. Educ. Psychol. Measurement 120, 37-46. Endicott, J. and Spitzer, R.L. (1978) A diagnostic interview: the Schedule for Affective Disorders and Schizophrenia. Arch. Gen. Psychiatry 35, 837-844. Endicott, J., Spitzer, R.L., Fleiss, J. and Cohen, J. (1981) The Global Assessment Scale: a procedure for measuring the overall severity of psychiatric disturbance. Arch. Gen. Psychiatry 38, 98-103. Gibbons, R.D., Clark, D.C. and Cavanaugh, S.A. (1985) Application of modem psychometric theory in psychiatric research. J. Psychiatr. Res. 19, 43-55. Katz, M.M. and Klerman, G.L. (1979) Overview of the clinical studies program. Am. J. Psychiatry 136, 49-70. Keller, M., Lavori, P.. Friedman, B., Nielsen, E., Endicott, J., McDonald-Scott, P. and Andreasen, N.(1987) The Longitudinal Interval Follow-up Evaluation. Arch. Gen. Psychiatry 44, 540-548. Lewine, R.R.J., Fogg, L.F. and Meltzer, H.Y. (1983) Assessment of negative and positive symptoms in schizophrenia. Schiz. Bull. 9, 368-376. Rasch, G. (1960) Probabilistic Models for Some Intelligence and Attainment Tests. University of Chicago Press, Chicago, IL. Spitzer, R.L., Endicott, J. and Robins, E. (1978) Research Diagnostic Criteria: rationale and reliability. Arch. Gen. Psychiatry 3, 773-785. Thissen, D. (1988) Multilog 5.1. Scientific Software, Moorseville IN. Winokur, G., Scharfetter, C. and Angst, J. (1985) Stability of psychotic symptomatology (delusions, hallucinations), affective syndromes, and schizophrenic symptoms (thought disorder, incongruent affect) over episodes in remitting psychoses. Eur. Arch. Psychiatry Neurol. Sci. 234, 303-307. Wright, B. and Stone, M. (1979) Best-Test Design: Rasch Measurement. MESA Press, Chicago, IL. Young, M.A., Keller, M.B., Lavori, P.W., Scheftner, W.A., Fawcett, J.A., Endicott, J. and Hirschfeld, R.M.A. (1987) Lack of stability of the RDC endogenous subtype in consecutive episodes of major depression. J. Affect. Disord. 12, 139-143.

Concordance of symptoms in recurrent depressive episodes.

The presence or absence of 12 depressive symptoms was examined in 93 bipolar and 108 unipolar patients who had two discrete episodes of major depressi...
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