A cluster analysis of manic states

Comprehensive

Psychiatry

(Official Journal of the American Psychopathological

Association)

MAY/JUNE 1991

VOL. 32, NO. 3

A Cluster Analysis

of Manic States

D.B. Double A cluster analysis was performed on 81 manically disturbed patients assessed at interview on items of manic symptomatology and general psychopathology. Four groups were obtained: (1) a mildly excited group, (2) a group characterized by elation and speech disturbance, (3) a small severely disturbed excited group, more schizophrenic than manic, and (4) a group characterized by aggressive overactivity. Copyright Fi 1991 by W.B. Saunders Company

T

HERE HAVE BEEN few studies that have used cluster analysis for classifying mania. Only one has specifically analyzed manic patients.’ Twenty patients were assessed and six clusters produced. All patients scored relatively high on manic items, but there were widespread differences on other scores and it was suggested that the traditional diagnosis of mania obscured diverse patterns of manic patients. Cluster analytic studies of unselected psychotic patients include some patients diagnosed as manic. For example, Lorr et al.’ divided a group of 100 chronically psychotic patients into six clusters, two of which seemed to have some bearing on the diagnosis of mania. They suggested one of these two types, which was called excited-grandiose, corresponded to the traditional euphoric manic, and the other type, which was called excited-hostile, had not been generally recognized in the literature. Different presentations of mania have been noted clinically. Kraepelin3 separated hypomania from mania in his original description of manic-depressive illness. He also proposed that mania could be divided into acute, delusional, and delirious subtypes. A theme of distinguishing elated and aggressive forms of mania can be discerned in the literature. It may be traced to Aretaeus in the third century, who observed that some manics are “cheerful and like to play” and others are “passionate and destructive.“4 In a similar way, Robertson in 1890 advocated the division of mania into hilarious and furious types. Beige1 and Murphy6 produced some empirical evidence to support the separation of mania into two forms, which they called elation-grandiose and paranoidFrom the Department of Psychiatry, University of Sheffield, Northern General Hospital, Sheffield, England. Address reprint requests to D.B. Double, M.A., M.R.C. Psych.. Lecturer in Psychiatry University of Sheffield, Northern General Hospital, Sheffield S57AV, England. Copyright 0 1991 by W B. Saunders Company OOIO-440X19113203-0005$03.00l0 Comprehensive

Psychiatry, Vol. 32, No. 3 (May/June),

1991: pp 187-194

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D.B. DOUBLE

destructive. The results of a factor analysis were seen as confirming the distinction.’ However, Loudon et al* failed to find evidence for a difference between these groups. The question of whether there are subtypes of mania remains undecided. Cluster analysis is the most appropriate statistical tool for deriving a categorical classification of psychopathology.9 It differs from factor analysis in that it seeks to identify groups of patients, rather than collections of symptoms. Like factor analysis, there is always some element of subjectivity in the method, as decisions need to be taken at various stages without clear-cut rules being available, which are necessarily any more objective than others, for example, when determining the number of clusters that forms the best subdivision. This study uses cluster analysis to propose a classification of manic states obtaining data from a larger series of patients than previous work.’ METHOD Subjects The subjects were 81 patients satisfying criteria (described below) for mania, admitted to Fulbourn Hospital, Cambridge between June 1987 and May 1988. There was no age limit in admitting patients to the study. All case notes of acute admissions to the hospital during this time were scrutinized for evidence of manic symptoms on admission. Any patient for whom the presence of manic symptoms could not clearly be excluded from these notes was interviewed to assess if the criteria for mania were met. The manic patients were further assessed by rating scales. Full details of the screening procedure are described in a previous report.“’ In brief, the case notes of 1,078 admissions were examined and 221 patients interviewed, producing a sample of 81 patients. There were 38 men and 43 women, with an age range of 21 to 81 years, mean 39.75. Twelve patients were first admissions with no previous admissions to a psychiatric hospital. Twenty-three patients in the series were readmitted for mania during the year of the study. All patients were interviewed within 3 days of admission to hospital.

Diagnostic Criteria The diagnostic criteria for mania used for inclusion in the study were those of Young et al.” Two of three symptoms from the criteria of Taylor and Abramsr’ are required: (1) elevated, expansive, or irritable mood (manic mood); (2) hyperactivity; and (3) rapid or pressured speech. Evidence is available from latent class analysis that only two of these three designated symptoms are required to make a diagnosis of mania.” There were 17 of the 81 patients in the series that had only two of the symptoms; the others fulfilled all three symptoms, thus meeting the stricter criteria of Taylor and Abrams.” Patients were excluded if there was an organic etiology or abuse of drugs. For example, a diagnosis of dementia or alcoholic intoxication as a cause of manic-like symptoms were reasons for exclusion. Different operational definitions of mania select different groups of manic patients.” The criteria used were deliberately broadly set to include a wide range of manic patients. The number of patients meeting the Research Diagnostic CriteriaI (RDC) was 48. A further 10 patients met the RDC criteria for schizoaffective disorder, manic type, and another eight met RDC criteria for hypomanic disorder. Thus, despite the apparently loose inclusion criteria, the vast majority of patients should be regarded as meeting recognized criteria for mania or hypomania. Consistent with this view is the evidence from latent class analysis that the addition of flight of ideas and grandiosity to the three designated symptoms of Taylor and Abrams does not alter the construct of mania.” Recent trends in diagnosis have tended to broaden the concept of mania. ” However, interpretation of the results may need to take into account that the series of patients could be seen as showing manic disturbance, rather than meeting more strictly defined criteria for mania.

A CLUSTER ANALYSIS

OF MANIC

STATES

189

Measures Ratings for each patient were made at interview by the same psychiatrist. Patients were rated on items from the Mania Rating Scale (MRS)‘” and the Comprehensive Psychopathological Rating Scale (CPRS).” The MRS is an 1l-item clinician-administered scale designed specifically to measure mania. Four of the items are given twice the weight of the other seven in an attempt to compensate for poor cooperation from severely ill patients. The CPRS has 67 items, only some of which are relevant to manic patients. It seemed important to measure general psychopathology, as well as specifically manic symptomatology, particularly as the criteria for inclusion in the study are broad. Thus, for example, more information is included in the analysis about psychotic symptomatology by including items from the CPRS, than if the analysis had been restricted to data from the MRS. One of the 67 items in the scale is a global rating of illness and another is the assumed reliability of the ratings. The scale steps 0, 1,2, and 3, are operationally defined for each item and half-steps were used, thus increasing the sensitivity of the scale.

Statistical Analysis All 11 items from the MRS were included in the analysis. Some of the items from the CPRS were rated as zero for all the manic patients, for example, because they relate specifically to nonmanic symptomatology. Only 26 of the 67 items had enough scores to be included in the analysis, items with zero or negligible scores being excluded. The 37 items were factor-analyzed and the principal components extracted, the criterion for stopping being an eigenvalue greater than one. The factor scores on these principal components were entered into the cluster analysis, rather than the original variables. Data were analyzed by the CLUSTAN programme.’ Ward’s hierarchical agglomerative methodlY was the method of cluster analysis used. Several Monte Carlo validation studies have tended to support the view that Ward’s method gives the best recovery of cluster structure.” Iterative reallocation by the k-means method was used to optimise the solution obtained.

RESULTS

The principal components analysis produced 10 factors that were entered into the cluster analysis. These factors accounted for 77.9% of the variance. The classification dendrogram obtained by Ward’s method is illustrated in Fig 1. From inspection of the diagram, clusters 1, 2, and 3 seem relatively stable and the four-cluster solution was chosen to be analyzed further. It suggests a hierarchical organization of patients, as shown in Fig 2. Reallocation switched 10 patients, producing final cluster sizes of 35 patients in cluster 1, 28 patients in cluster 2, three patients in cluster 3, and 15 patients in cluster 4. Characteristics of the reallocated groups were examined on the original 37 variables, and Table 1 shows the means of these items for the four groups. Interpretation of the clusters is necessarily subjective. Cluster 1 has the lowest rating for “global rating of illness” and several other items, particularly “overactivity, ” “language-thought disorder,” “content,” “appearance,” and “insight.” It seems to be a mildly disturbed group. Cluster 2 has the highest mean value for “elation,” which is an item in the CPRS rated by the report of the subject, and “elated mood,” which is an item rated by observation. The corresponding item from the MRS is “elevated mood” and, again, has its highest mean value in this cluster. “Pressure of speech,” “flight of ideas,” and “speech (rate and amount)” also have high scores. “Ideas of grandeur” has a higher value than in clusters 1 and 4. The cluster seems to contain an group characterized by elation and speech disturbance.

D.B. DOUBLE

190

80 70 ea t: 50 s: i

40

8 3 a

30

2a

a Fig 1. Dendrogram obtained by Ward’s Method.

CLUSTERS

Cluster 3 is a small group with only three members, which makes the mean values obtained less reliable. However, it does appear to be a distinctive group with high values for items particularly associated with schizophrenic symptomatology. For example, “content” and “insight” from the MRS and “disrupted thoughts,” “commenting voices,” “other auditory “other delusions,” hallucinations,” “ lack of appropriate emotion,” “perplexity,” “blank spells,” “incoherent speech,” “ mannerisms and postures,” and “hallucinatory behavior” from the CPRS all scored highly. The “global rating of illness” was also the highest of all the clusters. Some of the symptoms particularly associated with mania, like “pressure of speech” and “flight of ideas,” did not score highly. The cluster may be best described as a severely disturbed excited group, more

CluSterA

Cluster B

60 patients

21 patienta I

I

I Cluster 1 Fig 2. Hierarchical organization of patients.

31 ptlttents

Cluster 29 patients

I 2

cluster

I 3

3 patients

ClusteK

4

18 pat&nts

A CLUSTER ANALYSIS

191

OF MANIC STATES

Table 1. Characteristics

of Four Groups on Classification

Variables

(mean values)

Cluster

MRS items Elevated mood Increased motor activity-energy Sexual interest Sleep Irritability Speech (rate and amount) Language-thought disorder Content Disruptive-aggressive behavior Appearance Insight

1

2

3

4

1.8

2.8

2.3

1.9

2.0 0.5 :.:

2.6 1.3 2.3 1.9 5.0 2.1 3.7

2.3 0.7 1.0 4.0 3.3 2.7 8.0

3.2 1.3 1.9 6.1 3.9 1.6 3.3

0.5 0.5 1.7

1.0 :::

4.0 2.7 4.0

5.7 2.0 2.6

1.1 1.3 1.5 0.4 0.4 0.1 0.5 0.5 0.2 0.1 0.4 1.1 0.4 0.1 0.4 0.3 0.2 0.0 1.2 0.8 0.2 1.1 0.0 0.0 1.5 2.3

2.1 1.0 1.9 0.7 0.3 0.3 0.6 t?:

1.0 1.5 0.7 1.0 0.8 1.5 0.2 1.3 2.7 1.3 1.8 1.7 1.5 1.3 2.0 1.0 2.3 2.8 0.8 0.7 1.7 1.7 1.0 2.7 2.8 1.8

:*: 1:s 1.0 0.3 0.3 0.9 0.3 1.0 0.4 0.5 1.2 2.2 1.3 0.8 1.6 0.6 0.1 1.2 1.0 0.8 2.2 0.3 0.0 2.1 1.2

3:6 1.0 1.7

CPRS items Elation Hostile feelings Reduced sleep Increased sexual interest Feeling controlled Disrupted thoughts Ideas of persecution Ideas of grandeur Other delusions Commenting voices Other auditory hallucinations Elated mood Hostility Labile emotions Lack of appropriate emotion Distractibility Perplexity Blank spells Pressure of speech Flight of ideas Incoherent speech Overactivity Mannerisms and postures Hallucinatory behavior Global rating of illness Assumed reliability of rating

0:2 0.1 1.9 0.6 0.5 0.4 1.0 0.1 0.0 1.7 1.6 0.6 1.7 0.1 0.1 2.1 2.2

NOTE. Items on the MRS are rated from 0 to a maximum of 4, except for four items, i.e., irritability, speech (rate and amount), content, and disruptive-aggressive behavior, which are rated from 0 to a maximum of 8. Items on the CPRS are rated from 0 to a maximum of 3. Mean values of the patients in each cluster are, therefore, within these ranges.

schizophrenic than typically manic and may have only been included in the sample because of the broad nature of the operational criteria used. Cluster 4 has the highest mean values for “increased motor activity,” “irritability,” and “disruptive-aggressive behavior” from the MRS and “hostile feelings,” ‘chostility,” “distractibility,” and “overactivity” from the CPRS. It seems to include aggressive overactive patients. Discriminant function analyses were performed on the partitioned groups,

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*

Group

centroid

2

2

2222: 2m2 11 1 11111 1llM 1 11 1111 1 1 1111

22 2

2222 2

2 44

1

444 44*444 t

FUNCTION

4

1

Fig 3. Plot of patients on two discriminant function scores showing clusters 1,2, and 4.

again using the original variables, rather than the principal components. The scatterplot for clusters 1,2, and 4 is shown in Fig 3 with the two functions as axes. It indicates good separation of the groups. DISCUSSION

The results suggest that manic patients can be usefully separated into four groups. Using a broad definition of mania, the patients divide into (1) a mildly excited group, (2) a group characterized by elation and speech disturbance, (3) a small severely disturbed excited group, more schizophrenic than manic, and (4) a group characterized by aggressive overactivity. These results provide evidence, once the mildly excited group has been excluded, for the division of manic states into those that are predominantly elated and those that are predominantly aggressive. The mildly excited group could be seen as corresponding to hypomania, separated from mania by Kraepelin.3 The small severely disturbed group may be seen as patients with a schizophreniform disorder, which because of the excited nature of their presentation, meet the inclusion criteria for mania for the study. The groups may not precisely fit the “elation-grandiose” and “paranoiddestructive” descriptions of mania suggested by Murphy and Beigel’s factor analytic study.’ Although the elated group from the present cluster analysis does have a fairly high mean value for “ideas of grandeur,” the highest value is in the severely disturbed excited group. The item “ideas of persecution,” despite having the highest mean value in the overactive aggressive group, is not significantly different in the other clusters. The distinction between elated and aggressive forms of mania has been found by factor analysis, as well as cluster analysis.” Principal components analyses of

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both the clinician-administered MRS16 and the nurse-rated Manic-State Rating Scale” produced bipolar factors, with the extremes being characterized by aggression and elation. That a similar distinction has been found by cluster analysis could suggest that the principal components may reflect more than a dimension of mania and may be due to the different clusters of manic patients. The cluster and factor analyses are consistent, but the groupings produced do not precisely correspond. In particular, overactivity characterizes the aggressive cluster, but is only weakly associated with the aggressive pole in the principal components analysis of the MRS, and is strongly associated with the opposite pole in the analysis of the Manic-State Rating Scale. This finding of a difference between the results of the methods is reminiscent of studies in depression, where cluster analysis produces groupings consistent with the endogenous-reactive distinction found by factor analysis, but with some variations.22,u Such a finding is not inevitable, but may be commonly the case if clusters are real. Clustering methods are likely to be more useful in attempting to uncover a structure of psychopathology, as it is usually difficult to interpret principal components after the second factor, whereas there is not the same limitation in interpreting any number of clusters. The four-cluster solution has face validity as a classification of mania. Its clinical usefulness is less clear. Further studies are necessary to provide improved evidence of validity, and it would be particularly valuable if there were correlations with treatment and prognosis. The significance of the difference between the aggressive and elated forms of mania is uncertain. Although there is much more work on the multivariate analysis of depression, there is still a debate about its significancez4 and cluster analysis does not necessarily produce a more valid classification than can be created clinically. ACKNOWLEDGMENT I amgrateful to Professor

ES. Paykel and Dr. G.E. Berrios for their advice.

REFERENCES 1. Wittenborn JR, Weiss W: Patients diagnosed manic depressive psychosis-Manic state. J Consult Psycho1 16:193-198, 1952 2. Lorr M, Klett CJ, McNair DM: Syndromes of Psychosis. New York, NY, Pergamon, 1963 3. Kraepelin E: Manic-depressive insanity and paranoia. Edinburgh, England, Livingstone, 1921 4. Davidson GM: Manic-depressive psychosis: Theory and practice. J Nerv Ment Dis 12587-95, 1957 5. Robertson GM: Does mania include two distinct varieties of insanity and should it be subdivided? J Ment Sci 36:338-347, 1890 6. Beige1 A, Murphy DL: Assessing clinical characteristics of the manic state. Am J Psychiatry 128:688-694. 1971 7. Murphy DL. Beige1 A: Depression, elation and lithium carbonate responses in manic patient subgroups. Arch Gen Psychiatry 31:643-648, 1974 8. Loudon JB, Blackburn IM, Ashworth CM: A study of the symptomatology and course of manic illness using a new scale. Psycho1 Med 7:723-729,1977 9. Everitt BS: Cluster Analysis (ed 2). London, England, Halsted, 1980 10. Double DB: The factor structure of manic rating scales. J Affect Disord 18:113-119, 1990 11. Young MA, Abrams R. Taylor MA, et al: Establishing diagnostic criteria for mania. J Nerv Ment Dis 171:676-682,1983 12. Taylor MA, Abrams R: Manic states: A genetic study of early and late onset affective disorders, Arch Gen Psychiatry 28:656-658, 1973

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13. Brockington IF, Hillier VF, Francis AF, et al: Definitions of mania: Concordance and prediction of outcome. Am J Psychiatry 140:435-439,1983 14. Spitzer R, Endicott J, Robins E: Research Diagnostic Criteria. New York, NY, Biometrics Research, 1978 15. Pope HG, Lipinski JF: Diagnosis in schizophrenia and manic-depressive illness: A reassessment of the specificity of “schizophrenic” symptoms in the light of current research. Arch Gen Psychiatry 122:811-828,1978 16. Young RC, Biggs JT, Ziegler VE, et al: A rating scale for mania: Reliability, validity and sensitivity. Br J Psychiatry 133:429-435,1978 17. Asberg M, Montgomery SA, Perris C, et al: A comprehensive psychopathological rating scale. Acta Psychiatr Stand Suppl271:5-27, 1978 18. Wishart D: Clustan User Manual (ed 4). St Andrews, Scotland, University of St Andrews, 1987 19. Ward JH: Hierarchical grouping to optimize an objective function. J Am Stat Assoc 58:236-244, 1963 20. Milligan GW: A review of Monte Carlo tests of cluster analysis. Multivariate Behav Res 16:379-407,198l 21. Beige1 A, Murphy DL, Bunney WE: The Manic-State Rating Scale: Scale construction, reliability and validity. Arch Gen Psychiatry 25:256-262, 1971 22. Paykel ES: Classification of depressed patients: A cluster analysis derived grouping. Br J Psychiatry 118:275-288,197l 23. Grove WM, Andreasen NC, Young M, et al: Isolation and characterization of a nuclear depressive syndrome. Psycho1 Med 17:471-484,1987 24. Kendell RE: The classification of depression. A review of contemporary confusion. Br J Psychiatry 129:15-28,1976