Long-term inter-episode stability of syndromes underlying mania

Sato T, Bottlender R, Sievas M, Schröter A, Hecht S, Möller H-J. Long-term inter-episode stability of syndromes underlying mania. Acta Psychiatr Scand 2003: 108: 310–313. © Blackwell Munksgaard 2003. --> Objective: To explore the stability of diverse manic presentations across manic recurrences. Method: A total of 253 bipolar patients who experienced two or more hospitalizations, because of consecutive manic (or mixed) episodes, during a 20‐year period were included. All patients had second hospitalizations with an mean interval of 773 days, while 126 and 91 patients had third and fourth hospitalizations with mean intervals of 1559 and 2237 days from the index hospitalization, respectively. Seven symptom scores, previously factor‐validated, were calculated. Results: Depressive mood, irritable aggression, psychomotor/thought inhibition, mania, emotional lability/agitation and psychosis were moderately correlated across the index and subsequent hospitalizations. Conclusion: A majority of diverse manic presentations were stable across manic recurrences. The stability was not restricted to two consecutive recurrences but appeared widespread over the long‐term course of bipolar disorder. The finding may serve for the development of more effective long‐term treatment strategies and a clinically more reasonable subtyping of mania.

Keywords: mood disorders; bipolar disorder; mania

The diversity of manic presentations was recognized by Kraepelin and Weygandt ([[1]]). Recent factor‐analytic studies have improved the understanding of the manic diversity and have found similar symptom factors such as depressive mood, depressive inhibition, aggression and psychosis underlying mania ([[3]]). Surprisingly, their subsequent cluster‐analytic procedures revealed similar manic subtypes, i.e. mixed, aggressive and psychotic manic subtypes mainly characterized by depressive mood (and/or inhibition), aggression and psychosis, respectively ([[4]]). The studies reported that these manic subtypes were distinguishable in terms of several clinical variables including gender, short‐term outcome, social functioning and some biological factors ([[4]]).

The stability of these diverse presentations across several manic recurrences is of clinical and theoretical importance. There are several studies suggesting the stability of categorical manic‐mixed distinction in bipolar disorder ([[10]]), but the boundary of manic subtypes is believed to be dimensional ([[6], [13]]). The stability of other diverse features underlying mania has hardly been explored. Only one study calculated correlation coefficients of five symptom scores representing diverse manic presentations (dysphoria, psychosis, hedonic activation, irritable aggression and psychomotor activation) between two discrete manic episodes in 77 bipolar subjects: that all symptom scores were moderately correlated across the two episodes ([14]). This study explores the stability of seven symptom factors, which were found to be an underlying acute mania in the factor analysis ([5]), in a larger cohort of 253 bipolar patients.

The study attempted to explore the stability of seven previously factor‐validated symptom factors across several discrete manic recurrences in 253 patients with bipolar I disorder.

During a 20‐year period, from 1981 to 2001, 620 manic patients were admitted to our institute, at least once, for treatment. For every hospitalization of these patients, the clinical diagnosis, according to both ICD‐ and DSM‐systems, are systematically data based. Of the whole data base, patient data meeting the following inclusion criteria were selected: 1) patients having at least two hospitalizations because of DSM‐IV ([15]) bipolar I disorder, with manic or mixed episode currently; 2) these hospitalizations can be due to consecutive manic or mixed episodes of a patient, between which at least one depressive episode or a remittance phase longer than 2 months is interposed; 3) no severe somatic illness. Episodes prior to the publication of DSM‐IV were re‐diagnosed by reviewing medical records. This review was carried out before conducting the main statistical analyses described below. Finally, 253 patients (41% of all manic patients; women = 130) with at least two hospitalizations because of consecutive manic or mixed episodes were included. Their mean age at the first (index) hospitalization, because of manic or mixed episode during the period was 41.2 (SD = 14.6: range = 17–69) years. Their mean age at first affective onset was 29.3 (SD = 11.9) years. Approximately 20% (n = 51) had a lifetime history of alcohol or substance abuse. There was no significant difference in these variables between those included and other manic or mixed patients (n = 367), who were hospitalized only once at the institute during the period and were therefore excluded from the study. All included patients experienced a second hospitalization because of a manic or mixed episode, while 126 patients (women = 63) and 91 patients (women = 46) experienced third and fourth subsequent hospitalizations because of manic or mixed episodes, respectively. Mean intervals were 773 (SD = 826; range = 111–3024) days between first and second hospitalizations; 786 (SD = 766; range = 106–2876) days between second and third hospitalizations and 678 (SD = 721; range = 99–2754) days between third and fourth hospitalizations. The patients were treated as clinically appropriate during the study period.

A broad range of 196 psychiatric symptoms, which were present for 7 days prior to admission, were assessed on the day of the patients' admission using a standardized comprehensive rating system (the AMDP‐system) ([16]). Each item of the AMDP‐system is scored 0 (absent) to 3 (severe), using a semi‐structured interview method. A factor analysis was conducted for 37 AMDP symptoms in 576 manic patients and seven factors were found underlying the acute mania ([5]). Based on the results, seven scores (depressive mood, irritable aggression, sleep disturbance, psychomotor/thought inhibition, mania, emotional lability/agitation, and psychosis) were calculated by summing up raw item scores for each factor (Table 1). Spearman's correlation coefficients were calculated between the index and subsequent hospitalizations to determine inter‐episode stability of the seven symptom scores. The scores were compared between the index and subsequent hospitalizations using a non‐parametric statistical method for paired data (Wilcoxon's signed rank test). The AMDP‐raters were psychiatrists treating patients and were blind to prior AMDP‐ratings for each patient. The rated AMDP‐sheets were stored separately from medical records in the hospital.

1 Mean (SD) values and inter‐episode correlations of manic symptom factors

1 * Significant coefficients.

• 2 † The symptom factors were previously validated in 576 manic patients ([5]).
• 3 The item compositions of these scores are:
• 4 1) hopelessness, loss of vitality, inadequacy, depressed mood, feeling of guilt, rumination, suicide, delusion of guilt, feeling of impoverishment and anxiety for depressive mood;
• 5 2) irritability, aggression, dysphoria, uncooperativeness and lack of insight for irritable aggression;
• 6 3) terminal insomnia, insomnia, initial insomnia and middle insomnia for sleep disturbance;
• 7 4) retarded thought, inhibited thought, psychomotor inhibition and inhibited drive for psychomotor/thought inhibition;
• 8 5) exaggerated self‐esteem, euphoria, excessive social contact, flight of idea, increased drive, delusion of grandiosity and racing thoughts for mania;
• 9 6) emotional lability, distractivity, motor restlessness and agitation for emotional lability/agitation; and
• 10 7) persecutory delusion, auditory hallucination and suspiciousness for psychosis.
• 11 ‡ Each score was compared between the index hospitalization and subsequent hospitalizations using Wilcoxon signed rank tests (a non‐parametric test for paired data). No comparison produced a significant difference at P < 0.1.
• 12 § The alpha correction of the coefficients was made by Holm's method.

Table 1 demonstrates the mean (SD) values and correlation coefficients of the seven scores. All scores, other than sleep disturbance, were significantly correlated between the index and subsequent hospitalizations after Holm's alpha correction. The results indicate that a patient with a higher score on a symptom dimension is likely to score higher on that dimension in subsequent hospitalizations. The seven scores for the whole sample were not significantly different between the index and subsequent hospitalizations. The seven symptom scores for the index and second hospitalizations were further analysed using multiple regression analyses, with gender, age at onset, age at the index hospitalization, the intervention of a depressive episode and alcohol or substance abuse during a 1‐month period prior to hospitalization, being used as covariates, to know about the effects of these covariates on the correlations in the table. Of the patients, 143 (57%) had an interposition of a depressive episode between the index and second episodes. Computed partial correlations of the symptoms scores were quite similar to the correlations as shown in the table. None of the covariates significantly contributed to any symptom score at the second hospitalization.

The results indicate that depressive mood, irritable aggression, psychomotor/thought inhibition, mania, emotional lability/agitation and psychosis, representing diverse manic presentations, are significantly stable across two to four manic recurrences. The stability was not restricted to two consecutive recurrences but appeared widespread over the long‐term course of bipolar disorder. Additionally, the multiple regression analyses indicated that the significant stability of manic presentations was not largely affected by the factors such as gender, age at onset, the interposition of a depressive episode and alcohol, or substance abuse prior to hospitalization. Given some evidence that the diverse symptom factors are correlated to variables, including acute treatment outcome and social functioning ([[4]]), these findings may serve for the development of more effective long‐term treatment strategies in bipolar disorder and a clinically more reasonable subtyping of mania in future. The moderate correlations of the symptom factors across several manic recurrences in this study however suggest that manic presentations are not predicted by symptom profiles only, in previous manic episodes.

This study method was retrospective. However, the fact that the raters were blind to prior psychiatric ratings may have minimized the bias potentially caused by the design, although a large, careful prospective study is needed in future. That the study subjects were not fully medication‐free at the time of psychiatric ratings may be another possible limitation. However, most manic patients are receiving unspecific medications before their admission these days. These results might be interpreted as a reflection of the natural history of average manic patients receiving unspecific medications. Naturally, further study should investigate potential associations between long‐term pharmacological treatments and clinical presentations in bipolar patients.