Journa! of Affeectilv Disorders, 24 (1992) 35-41 0 1992 Elsevier Science Publishers B.V. All rights reserved 01650327/92/$05.00
JAD 00862
ourse of bipolar disorder in eastern India R. Khanna, N. Cupta and S. Shanker Department of Psychiatry, Central htiiute
of Psychiatry, Kanke, Ranchi 834006, India
(Received 17 July lY9f) (Revision received 4 October 1991) (Accepted 7 October 1991)
Summary The life course of affective episodes was determined for 95 consecutively admitted patients from eastern India fulfilling RDC criteria for definite mania during the current episode, using SADS-L interviews. There was a significantly greater frequency of manic compared to depressive relapses. Presentation as recurrent mania was very common. The total numbers of affective and manic episodes were significan ?‘v higher among those with recurrent mania and in cases where the first illness episode was manic.
Key words: Bipolar disorder; Recurrent mania; Life course
Introduction The bipolar-unipolar distinction is probably the most accepted system of classifying affective disorders. This distinction places its primary emphasis on the occurrence of mania. Consequently bipolar disorder has come to include all patients with mania whether or not they were previousiy depressed. In most inpatient studies, the ratio of bipolar to unipolar cases has ranged from 1: 10 to 1: 3. Most of these reports come from the northern and western countries. Clayton (1981) thought
Address for correspondence: Dr. Rakesh Khanna, M.D., Central Institute of Psychiatry, Kanke, Ranchi 834006, India. Tel.: 301030.
that these figures were likely to change, as psychiatrists become more astute in recognising mania and hypomaGa. Concern has also been raised about the failure of clinicians to elicit information about prior manic or hypomanic episodes (Egeland, 1983). In the Amish study (Egeland, 1983) the ratio of bipolar to unipolar disorders changed from 1: 2 to 1 : 1 following the use of the Schedule for Affective Disorder and SchizophreniaLifetime version (SADS-L, Endicott and Spitzer, 1978). Cross-cultural comparisons of rhe course of bipolar disorders are important. There are a few studies which report a preponderance of mania in certain cultural groups and geographical locations. Bazzoui (1970) found that 44% of patients admitted with affective disorder in Iraq were
Gershon and Liebowitz (1975) noted the relatively high proportion (45%) of patients in a Jewish popuiation of Jerusalem admitted with bipolar affective disorder. This means that every other depressed patient in Jerusalem is bipolar, whereas only every fifth depressed patient in Sweden is bipolar (Belmaker and Van Praag, 1980). Leff et al. (1976) found age-specific (25-49 years) annual first admission rates for West-Indian male immigrants to the UK to be six times that of the native-born Camber-well males (23.9/100,000 vs. 3.7/100,000). Makanjuola (1985, 1989) has described the occurrence of mania in Yoruba Nigerians, predominantly as a recurrent manic disorder. In India, there has been a paucity of research on bipolar disorders. One reason for this neglect may be the widespread use of ICD-9, which does not make explicit the unipolar-bipolar distinction. There has been a marked excess of admissions for mania compared to depressive disorders at our institute. Similar trends are reported from other Indian centres. In contrast to the western literature, there is a concern for failure to elicit information about depressive episodes. The purpose of our study was to investigate the life course of bipolar disorder in a group of consecutively admitted manic patients, using a structured Interview schedule. bipoiars.
Methods
The study was carried out at the Central Instianchi, one of the oldest psychiatric hospitals and one of the main postgraduate training centres of India. This institute has an unlimited catchment area and serves both as a walk-in clinic and as a referral centre. The majority of patients come from the state of Bihar and adjoining areas of the neighbouring states. The institute has a bed strength of 643, with an annual outpatient attendance of over 10,000 and an admission rate of over 1500 per annum. All patients admitted between 1 September 1989 and 6 December 1989 were screened, except those admitted on Sundays and public holidays. Cases who fulfilled RDC criteria for definite manic disorder were included, provided they were between 17 and 60 years of age and were accom-
panied by at least one close relative, capable of giving a reliable lifetime history of past illness episodes. SADS-L interviews were conducted to collect information regarding the current and previous episodes. Past history was supplemented by hospital records (if the patient had been treated at this institute in the past) and previous clinical notes of treating psychiatrists, when available. While interviewing the relatives, in order to assess the time dimension, various anchor points (personal, familial, sociaIJ were used. For an affective episode, the subject must have shown mood dysregularion of sufficient intensity and duration to be clearljr differentiated from his normal state. Manic and depressive episodes were counted separately even when one followed the other, without reaching premorbid levels of functioning. Two consecutive manic or depressive episodes were counted separ.ueiy only when they were separated by an asymptomatic interval of at least 2 months. No attempt was made to grade the severity of the affective episodes. Following collection of retrospective data, a life chart was made for individual cases, and was confirmed with the patient, once he had reached a euthymic state. Only episodes distinctly remembered by the patient and documented by at least one outside source (hospital records, physician notes, close relative) were included for making the final life chart. A total of 329 patients were admitted during the period of study, including 15 cases admitted on Sundays or public holidays. Out of 314 cases screened, 115 (33.6%) between the ages 17 and 60 years fulfilled RDC criteria for definite manic disorder. Seventeen cases (nine males and eight fcmaies) were accompanied by persons (spouse, colleague or distant relative) not ca,pabIe of providing reliable information for the SADS-L. Three more cases were later excluded because of a lack of consensus on diagnosis between the research team and the treating team. Differences involved ihe interpretation of mood-incongruent psychotic symptoms. In this paper w0 present information regarding the age and sex distribution of the sample and retrospectively derived variables, e.g., age at onset of illness, duration of illness, number of episodes (manic, depressive, total), episodes per
37
year, type of onset (mania/ depression), phases of illness (uniphasic/ polyphasic) and changes in well intervals (sensitisation/ non-sensitisation). Recurrent manias are compared with true bipolars, and those with a first episode of mania compared with those with a first episode of depression. One-way analysis of variance was used for comparing continuous variables. Categorical variables were evaluated with chi-square tests with Yates’ correction.
TABLE 1 NUMBER OF EPISODES IN 9.5 BIPOLAR PATIENTS Episodes
Mania only Mania and depression Total
1
2
3
4 or more
25
19 4 23
8 5 13
15 19 34
25
esults The study sample consisted of 80 male and 15 female subjects (a significant preponderance of males: x2 = 44.47, P < 0.001). The mean age of the sample at the time of current hospitalisation was 31.82 ( t_ 11.84) years. The mean age of onset of illness was 26.9 ( + 11.3) years, with a median of 22 yea :s and the most frequent age interval 15-19 followed by 20-24 years. Twenty-five (26.3%) patients were admitted for their first manic episode, while 23, 13 and 34 patients were admitted for the second, third, and fourth or more illness episodes respectively (Table 1). These 95 cases had a total of 321 lifetime illness episodes of which 283 (88.2%) were manic, and 38 (11.8%) were depressive, The number of manic episodes per person varied from one to 16 (one episode 29, two episodes 27, three 15, four 7, five 2, six 5, seven 6, eight 1, nine 1, twelve 1, sixteen 11 and
the number of depressive episodes varied from one to two (one episode 18, two episodes 10). The mean number of episodes per person was 3.4 + 2.7 (manic 3 + 2.5 and depressive 0.4 rtr0.7). The mean number of siblings per person was 4.95 f 1.87 and the mean birth order 2.76 + 1.9. Among those with a past history of illness (n = 70) the mean duration oi’ illness was 6.3 (k6.5) years, and an episode frequency oL’0.96 ( f 0.53) episode per year. 1;:: first illness episode was manic in 83% of the cases. A biphasic illness was seen in only 11 of these 70 cases (15.7%), There was not a single case with a polyphasic (more than biphasic) illness or with a rapid-cycling affective disorder. Out of the 47 patients with three or more lifetime illness episodes, 30 (64%) showed a sensitisation pattern (subsequent inter-episode intervals shorter than initial intervals).
TABLE 2 COMPARATIVE
DATA ON RECURRENT
MANIA AND TRUE BIPOLARITY
--
Sex (M : F) Age at current hospitalisation (mean k SD) Age at ouset of illness (mean + SD) Years ill (mean f SD) Number of episodes (mean + SD) Total Mania Depression Episodes per year (mean _t SD) Course (sensitisation: non-sensitisation) Number of siblings (mean f SD) Birth order (mean + SD)
Recurrent mania (n = 15)
True bipolarity (n = 19)
Statistical analysis (as appropriate)
12:3 38 511.3 28.3 + 9.1 9.5 * 5
16:3 31.4 f9.3 22.8 f8.8 8.7 k7.8
x2 = - 0.009, NS F = 3.52, NS F = 3.25, NS F-O.ll,NS
7.2 F 3.2 7.2 + 3.2 0 0.91 f 0.5 12:3 5 +1.8 2.5 f 2
5.4 +1.6 3.9 +I.6 1.5 +0.5 0.95 + 0.5 12:7 5.1 f1.6 2.8 k1.3
F = 4.44. P < 0.05 F = 15.42, P C 0.01 F = 0.04, NS x2 = 0.47, NS F = 0.03, NS F = 0.5, NS
38
episode was that of depression and for 16 (57.1%) the first episode was that of mania. Of those who switched from depression to mania, 11 (91.6%) did so in the second episode and one (8.4%) in the third episode. Of those with a first manic episode, for nine (56.3%) the second episode was depressive. For two each the third or fourth episode was that of depression, while the fifth, sixth or seventh episode was the first depressive episode for one patient each. Those patients whose first illness episode was manic had significantly more total illness episodes and, a larger number of manic episodes. All other comparisons were statistically non-significant (Table 3).
Recurrent ,mania 1s. true bipolar
The frequency of episodes in patients with mania only and those with mania and depression is shown in Table 1. The prevalence of recurrent mania in this saniple was high. 60% of the sample (42 out of 70) had two manic episodes without an episode of depression. Among those with three lifetime episodes of illness, 48.9% (23 out of 47) had only manic episodes. Even when unipolar mania was defined as four or more lifetime episodes of mania without any episode of depression, 44% (15 out of 34) fulfilled the criterion. The results of comparison between recurrent mania (defined by the occurrence of four manic episodes without an episode of depression vs. true bipolars) are shown in Table 2. The trend was for the recurrently manic group to be older at the time of the index evaluation and at age of onset. Chi-square evaluation comparing recurrent manics and true bipolars above and below the median age of onset revealed a statistically significant difference between the two groups (x2 = 4.29, P < 0.05). Recurrent manics had significantly more total illness episodes and a larger number of manic episodes compared to true bipolars. All other comparisons were non-significant.
Discussion
One of the most striking features of our sample is the marked prepo,zderance of male subjects (M : F = 80 : 15). Proportionately more females were not included in the study because of a lack of reliable informants (M : F = 9: 8). Again proportionately more females failed to fulfill RDC criteria for definite mania compared to males. Evidence suggests that female schizophrenics at least exhibit more atypical symptoms than male schizophrenics (Lewine, 1981). Further, the triterion for inclusion in our study was a diagnosis of mania at the time of index admission. Perhaps one of the most consistent findings in psychiatric
Switch to the opposite pole
Out of the 28 cases who had a history of both mania and depression, for 12 (42.9%) the first TABLE 3 COMPARATIVE DATA ON PATIENTS WHO SWITCHED SWITCHED FROM MANIA TO DEPRESSION
Sex (M : F)
Age at current hospitalisation (mean + SD) Age at onset of illness (mean i SD) Years ill (mean + SD) Number of episodes (mean + SD) Total Mania Depression Episodes per year (mean + SD) Illness phase tbiphasic: uniphasic) Course (sensitisation: non-sensitisation) Number of siblings (mean + SD) Birth order (mean f SD)
FROM DEPRESSION
TO MANIA AND
THOSE WHO
Depression to mania tn = 12)
(n = 16)
10:2 29.2+ 11.1 21.8k 9.4 7.7* 10.1
12:4 32.8k9.3 25.7+9.5 7.1 -15.8
,$ = 0.004, NS F = 0.86, NS I; = 1.19, NS F = 0.03, NS
5.1+2 3.8+ 1.8 1.3~0.5 0.9+0.4 6: 10 II:5 5.5 + 1,4 2.9+ 1.3
F = 4.56, P < 0.05 F = 6.72, P < 0.05 F = 0.42, NS
3.7, 2.3f 1.4+ 1.2f 4:8 6:6 4.5+ 3 +
1.5 1.1 0.5 0.7
2.2 2.4
Mania to depression
Statistical analysis “C1
F=2,NS
x2 = 0.028, NS x2 = 1.02, NS F = 2.26, NS F = 0.006, NS
39
epidemiology is that women suffer from depression more frequently than men (Weissman and Klerman, 1985). Bland et al. (1988) reported a higher rate of manic episodes for men (0.7%) than women (0.4%). Some male excess has been reported in studies on unipolar mania (Abrams and Taylor, 1974; Nurnberger et al., 1979; Makanjuola, 1985). The sex difference in the admission rates at our institute is approximately four males to one female. The low female admission rate may reflect socio-cultural determinants of hospital admissions. In India, the existing number of mental hospital beds is in the ratio of one bed to approximately 40,000 people. Admission to mental hospitals probably reflects only the incidence of mental illness surpassing the tolerance level of the immediate environment. There is evident. from the literature that males tend to have more severe manias, and a greater number of hospitalisations for mania (Winokur et al., 1969; Angst, 1978; Roy-Byrne et al., 1985). One of the best documented sex differences in human behaviour is a greater tendency for the male to show aggressive behaviour (Ember, 1981). Other socio-cultural factors such as social role assignment and economic compulsions may be important. The female is more likely to be a housekeeper and in the event of illness her role may be more effectively taken over by significant others living within the extended family system. The male is more likely to be the wage-earner and will get immediate attention when his wage-earning capacity is affected. Admission to a psychiatric hospital is often considered a stigma for the patient and his family. In a social context where marriages are largely ‘arranged’ through the social network, a young woman, if hospitalised, may seriously harm her chances of an appropriate matrimonial placement. The mean age of onset of illness was 26.9 ( & 11.3) years, which is in keeping with other hospital-based studies (Nurnberger et al., 1979; Pfohl et al., 1982; Joyce, 1984; Roy-Byrne et al., 1985) but higher than those seen in recent community-based studies (Weissman et al., 1988; Bland et al., 1988). The median age of onset (22 years) was similar to reports in the literature (Winokur et al., 1969: Joyce, 1984; Burke et al.,
1990). The mean age of onset of illness was significantly lower for females. Review of the literature generally suggests chat patients with a later age of onset are predominantly male (Swift, 1907; Kraepelin, 1921; Angst, 1978). Those with recurrent mania had a significantly later age of onset than true bipolars. The mean number of episodes per person was 3.4 f 2.7 (manic 3 + 2.5 and depressive 0.4 f 0.7). While the number of manic episodes per person ranged from one to 16, the number of depressive episodes ranged from one to two only. 60%, 48.9%, and 44% of the cases had two, three and four or more manic episodes without a major depressive episode. Those with recurrent mania (more than four episodes of mania without depression) had significantly more total illness episodes and a larger number of manic episodes than true bipolars. Though the frequency of episodes varies over time and between patients, a review of the literature generally suggests a higher percentage of episodes that are depressive (RoyByrne et al., 1985). Kraepelin (1921) noted that purely depressive and circular insanity were incomparably much more frequent than pure periodic mania. Perris (1982) found only 17 cases of unipolar mania in a sample of 1539 cases. Others (Abrams and Taylor, 1974; Nurnberger et al., 1979; Abrams et al., 1979; Pfohl et al., 1982) have reported higher figures based only on the occurrence of one or two manic episodes without depression. Very few studies have shown an incidence of mania higher than that of depression. In the sample studied by Winokur et al. (1969) the mean number of manic episodes was 2.6 and that of depressive episodes 1.9 per person. Carlsson et al. (1974) reported 3.7 manic and 2.1 depressive episodes per person. Mendlewicz et al. (1972) noted that for patients with a positive family history there were two admissions for mania for every admission for depression. In contrast, among those with no family history there were three admissions for depression for every one for mania. Recent studies, using well defined diagnostic criteria and outcome measures, reveal a higher incidence of recurrent mania. COryell et al. (1989) followed up 53 bipolar I patients over 5 years, during which time 32 (60.4%) had at least
40
one episode of mania or schizoaffective mania, and fewer depressive relapses. Harrow et al. (1990) found 42% of 73 manic patients to have a full manic syndrome, another 13% had some manic symptoms and slightly over 30% had a full depressive syndrome during the follow-up year. In another naturalistic follow-up study of 75 manic patients, Tohen et al. (1990) found manic relapses to far outweigh the depressive. The first illness episode was manic in 83% of our cases. Goodwin and Jamison (1984) on taking an average of numerous studies found that around 50% started the illness with mania. Only uniphasic illness periods were seen in 84.3% of all cases. Even among those with biphasic illness, only two showed such a pattern in more than one illness period. 70% and 60% of the illness periods were reported to be uniphasic by Angst (1978) and Roy-Byrne et al. (1985). Winokur et al. (1969) found that 51% of the manic episodes were preceded and 57% followed by a depressive phase of at least 1 month. In the prospective study by Tohen et al. (1990) only 15% of the patients cycled into depression before recovery to the euthymic state. None of our cases had rapid-cycling affective disorder. This could be because of the low frequency of depressive disorder, or reduced chances of treatment with tricyclics, which is known to precipitate rapid cycling (Wehr and Goodwin, 1987). A switch from depression to mania occurred early: 11 out of 12 (91.7%) switciied at the time of the second episode itself. The switch from mania to depression was more gradual, the first depressive episode was seen as late as after the seventh manic episode. Those who switched from mania to depression had significantly more total illness episodes and a larger number of manic episodes. Perris (1968) and Roy-Byrne et al. (1985) also reported a higher frequency of subsequent manias in patients with a first manic episode. Venkoba-Rao and Nammalvar (197’1)followed up 109 patients in southern India for a period of 3-13 years; 42 of these switched from unipolar to bipolar illness, 64%, 32% and 3% after the first, second, and third episode respectively. Recurrences were more frequent among those who switched to bipolarity and manic episodes were more frequent than depressive episodes.
Our results may be more relevant to hospitalised bipolar patients in developing countries. Hospital admission rates are low and it is probable that only those patients with severe and socially difficult behaviour are hospitalised. This would have the effect of decreasing admission for women and those with depression. Leonhard (1986) has proposed a link between the more common occurrence of mania in developing countries and the presence of relatively many siblings. Too much stimulation in early childhood may create a predisposition which leads to a greater chance of developing mania in later life. In our samp!e the mean number of siblings per index patient was five. The high density of the population, poor housing and consequent overcrowding may increase the chances of overstimulation. Besides, the longitudinal course of bipolar disorder may represent a complex interaction between genetic and environmental factors. The environmental factors may include variables such as season (day length, number of hours of sunshine, air ionisation, ambient temperature and relative humidity), exposure to viruses, diet, etc. The influence of such factors is currently not well understood. Studies conducted in different geographical regions may provide further insight into the possible role of these factors in bipolar disorder. eferences Abrams, R. and Taylor, M.A. (1974) Unipolar mania. Arch. Gen. Psychiatry 30, 441-443. Abrams, R., Taylor, M.A., Hayman, M.A. and Krishna, N.R. (1979) Unipolar mania revisited. J. Affect. Disord. 1, 5968.\ Angst, J. (1978) The course of affective disorders. II. Typology of bipolar manic depressive illness. Arch. Psychiatric Nervenkr. 226, 65-74. Bazzoui, W. (1970) Affective disorders in Iraq. Br. J. Psychiatry 117, 195-203. Belmaker, R.H. and Van Praag, H.M. (1980) Mania: An Evolving Concept. Spectrum, New York, NY. Bland, R.C., Qrn, H. and Newman, SC. (1988) Life time prevalence of psychiatric disorders in Edmonton. Acta Psychiatr. Stand. 77 (Suppl. 338), 24-32. Burke, K.C.. Burke, J.D., Regier, D.A. and Rae, D.S. (1990) Age of onset of selected mental disorders in five community populations. Arch. Gen. Psychiatry 47, 511-518. Carlsson, GA., Kotin, J., Davenport, Y.B. and Adland, M. (1974) Follow up of 53 bipolar manic depressive patients. Br. J. Psychiatry 124, 134-139.
41 Clayton, P.J. (1981) The epidemiology of bipolar affective disorder. Compr. Psychiatry 22, 31-43. Coryell, W., Keller, M., Endicott, J., Andreasen, N., Clayton, P. and Hirschfield, R. (1989) Bipolar II illness: course and outcome over a five year period. Psychol. Med. 19. 129141. Egeland, J.A. (1983) Bipolarity: the iceberg of affective disorders? Compr. Psychiatry 24, 337-344. Ember, C. (1981) A cross-cul!ural perspective on sex difference. In: R. Munroe, R. Munroe and B. Whitney (Eds.), Handbook of Cross Cultural Human Development. Gorland, New York, NY. Endicott, J. and Spitzer, R.L. (1978) A diagnostic interview: the Schedule for Affective Disorders and Schizophrenia. Arch. Gen. Psychiatry 35, 837-844. Gershon, E.S. and Liebowitz, J.H. (1975) Sociocultural and demographic correlation of affective disorders in Jerusalem., J. Psychiatr. Res. ;2, 37-50. Goodwin, F.K. and Jamison. K.R. (1984) The natural course of manic depressive illness. In: R.M. Post and J.C. Ballenger (Eds.), Neurobiology of Mood Disorders. Williams & Wilkins, Baltimore, MD, pp. 20-38. Harrow, M., Goldberg, J.F., Grossman, L.S. and Meltzer, H.Y. (1990) Outcome in manic disorder: a naturalistic follow-up study. Arch. Gen. Psychiatry 47, 665-671. Joyce, P.R. (1984) Age of onset in bipolar affective disorder and misdiagnosis as schizophrenia. Psychol. Med. 14. 145149. Kraepelin, E. (1921) Manic Depressive Insanity and Paranoia. Livingstone. Edinburgh. Leff, J.P., Fischer, M. and Bertelsen, A. (1976) A cross national epidemiological study of mania. Br. J. Psychiatry 129.428-442. Leonhard, E. (1986) Different causative factors in different forms of schizophrenia. Br. J. Psychiatry 149, l-6. Lewine, R.R.J. (1981) Sex differences in schizophrenia: timing or subtypes? Psychol. Bull. 90, 432-444. Makanjuola, R.O.A. (1985) Recurrent unipolar manic disorder in Yoruba Nigerians: further evidence. Br. J. Psychiatry 147,434-432.
Makanjuola, R.O.A. (1989) Sociocultural parameters in Yoruba Nigerian patients with affective disorders. Br. J. Psychiatry 155, 337-340. Mendlewicz, J., Fieve, R.R., Rainer, J.D. and Fleiss, J.L. (1972) Manic depressive illness: a comparative study of patients with and without a family history. Br. J. Psychiatry 120,523-530. Nurnberger, J., Roose, S.P., Dunner, D.L. and Fieve, R.R. (1979) Unipolar mania: a distinct clinical entity? Am. J. Psychiatry 136, 1420-1423. Perris, C. (1968) The course of depressive psychoses. Acta Psychiatr. Stand. 44, 238-248. Perris, C. (1982) The distinction between bipolar and unipolar affective disorders. In: E.S. Paykel (Ed.), Handbook of Affective Disorders. Churchill Livingstone, Edinburgh, pp. 45-68. Pfohl, B., Vesquez, N. and Nasrallah, H. (1982) Unipolar vs. bipolar mania: a review of 247 patients. Br. J. Psychiatry 141, 4538-458. Roy-Byrne, P., Post, R.M. and Uhde, T.W. (1985) The longitudinal course of recurrent affective illness. Acta Psychiatr. Stand. 71 (Suppl. 3171, l-34. Swift, H.M. (1907) The prognosis of recurrent insanity of manic-depressive type. Am. J. Insanity 64, 311-326. Tohen, M., Waternaux, C.M. and Tsuang, M.T. (1990) Outcome in mania. Arch. Gen. Psychiatry 47, 1106-l 111. Venkoba-Rao, A. and Nammalvar, N. (1977) The course and outcome of depressive illness. Br. J. Psychiatry 130, 392396. Wehr, T.A. and Goodwin, F.K. (1987) Can antidepressants cause mania or worsen the course of affective illness? Am. J. Psychiatry 144, 1403-1411. Weissman, M.M. and Klerman, G.L. (1985) Gender and depression. Trends Neurosci. 8, 416-420. Weissman, M.M., Leaf, P.J., Tischler, G.L., Blazer, D.G., Karno, M., Bruce, M.L. and Florio, L.P. (1988) Affective disorders in five United States communities. Psychol. Med. 18, 141-153. Winokur, G., Clayton, P.J. and Reich, T. (1969) Manic Depressive illness. Mosby, St. Louis, MO.
JAD 00862
ourse of bipolar disorder in eastern India R. Khanna, N. Cupta and S. Shanker Department of Psychiatry, Central htiiute
of Psychiatry, Kanke, Ranchi 834006, India
(Received 17 July lY9f) (Revision received 4 October 1991) (Accepted 7 October 1991)
Summary The life course of affective episodes was determined for 95 consecutively admitted patients from eastern India fulfilling RDC criteria for definite mania during the current episode, using SADS-L interviews. There was a significantly greater frequency of manic compared to depressive relapses. Presentation as recurrent mania was very common. The total numbers of affective and manic episodes were significan ?‘v higher among those with recurrent mania and in cases where the first illness episode was manic.
Key words: Bipolar disorder; Recurrent mania; Life course
Introduction The bipolar-unipolar distinction is probably the most accepted system of classifying affective disorders. This distinction places its primary emphasis on the occurrence of mania. Consequently bipolar disorder has come to include all patients with mania whether or not they were previousiy depressed. In most inpatient studies, the ratio of bipolar to unipolar cases has ranged from 1: 10 to 1: 3. Most of these reports come from the northern and western countries. Clayton (1981) thought
Address for correspondence: Dr. Rakesh Khanna, M.D., Central Institute of Psychiatry, Kanke, Ranchi 834006, India. Tel.: 301030.
that these figures were likely to change, as psychiatrists become more astute in recognising mania and hypomaGa. Concern has also been raised about the failure of clinicians to elicit information about prior manic or hypomanic episodes (Egeland, 1983). In the Amish study (Egeland, 1983) the ratio of bipolar to unipolar disorders changed from 1: 2 to 1 : 1 following the use of the Schedule for Affective Disorder and SchizophreniaLifetime version (SADS-L, Endicott and Spitzer, 1978). Cross-cultural comparisons of rhe course of bipolar disorders are important. There are a few studies which report a preponderance of mania in certain cultural groups and geographical locations. Bazzoui (1970) found that 44% of patients admitted with affective disorder in Iraq were
Gershon and Liebowitz (1975) noted the relatively high proportion (45%) of patients in a Jewish popuiation of Jerusalem admitted with bipolar affective disorder. This means that every other depressed patient in Jerusalem is bipolar, whereas only every fifth depressed patient in Sweden is bipolar (Belmaker and Van Praag, 1980). Leff et al. (1976) found age-specific (25-49 years) annual first admission rates for West-Indian male immigrants to the UK to be six times that of the native-born Camber-well males (23.9/100,000 vs. 3.7/100,000). Makanjuola (1985, 1989) has described the occurrence of mania in Yoruba Nigerians, predominantly as a recurrent manic disorder. In India, there has been a paucity of research on bipolar disorders. One reason for this neglect may be the widespread use of ICD-9, which does not make explicit the unipolar-bipolar distinction. There has been a marked excess of admissions for mania compared to depressive disorders at our institute. Similar trends are reported from other Indian centres. In contrast to the western literature, there is a concern for failure to elicit information about depressive episodes. The purpose of our study was to investigate the life course of bipolar disorder in a group of consecutively admitted manic patients, using a structured Interview schedule. bipoiars.
Methods
The study was carried out at the Central Instianchi, one of the oldest psychiatric hospitals and one of the main postgraduate training centres of India. This institute has an unlimited catchment area and serves both as a walk-in clinic and as a referral centre. The majority of patients come from the state of Bihar and adjoining areas of the neighbouring states. The institute has a bed strength of 643, with an annual outpatient attendance of over 10,000 and an admission rate of over 1500 per annum. All patients admitted between 1 September 1989 and 6 December 1989 were screened, except those admitted on Sundays and public holidays. Cases who fulfilled RDC criteria for definite manic disorder were included, provided they were between 17 and 60 years of age and were accom-
panied by at least one close relative, capable of giving a reliable lifetime history of past illness episodes. SADS-L interviews were conducted to collect information regarding the current and previous episodes. Past history was supplemented by hospital records (if the patient had been treated at this institute in the past) and previous clinical notes of treating psychiatrists, when available. While interviewing the relatives, in order to assess the time dimension, various anchor points (personal, familial, sociaIJ were used. For an affective episode, the subject must have shown mood dysregularion of sufficient intensity and duration to be clearljr differentiated from his normal state. Manic and depressive episodes were counted separately even when one followed the other, without reaching premorbid levels of functioning. Two consecutive manic or depressive episodes were counted separ.ueiy only when they were separated by an asymptomatic interval of at least 2 months. No attempt was made to grade the severity of the affective episodes. Following collection of retrospective data, a life chart was made for individual cases, and was confirmed with the patient, once he had reached a euthymic state. Only episodes distinctly remembered by the patient and documented by at least one outside source (hospital records, physician notes, close relative) were included for making the final life chart. A total of 329 patients were admitted during the period of study, including 15 cases admitted on Sundays or public holidays. Out of 314 cases screened, 115 (33.6%) between the ages 17 and 60 years fulfilled RDC criteria for definite manic disorder. Seventeen cases (nine males and eight fcmaies) were accompanied by persons (spouse, colleague or distant relative) not ca,pabIe of providing reliable information for the SADS-L. Three more cases were later excluded because of a lack of consensus on diagnosis between the research team and the treating team. Differences involved ihe interpretation of mood-incongruent psychotic symptoms. In this paper w0 present information regarding the age and sex distribution of the sample and retrospectively derived variables, e.g., age at onset of illness, duration of illness, number of episodes (manic, depressive, total), episodes per
37
year, type of onset (mania/ depression), phases of illness (uniphasic/ polyphasic) and changes in well intervals (sensitisation/ non-sensitisation). Recurrent manias are compared with true bipolars, and those with a first episode of mania compared with those with a first episode of depression. One-way analysis of variance was used for comparing continuous variables. Categorical variables were evaluated with chi-square tests with Yates’ correction.
TABLE 1 NUMBER OF EPISODES IN 9.5 BIPOLAR PATIENTS Episodes
Mania only Mania and depression Total
1
2
3
4 or more
25
19 4 23
8 5 13
15 19 34
25
esults The study sample consisted of 80 male and 15 female subjects (a significant preponderance of males: x2 = 44.47, P < 0.001). The mean age of the sample at the time of current hospitalisation was 31.82 ( t_ 11.84) years. The mean age of onset of illness was 26.9 ( + 11.3) years, with a median of 22 yea :s and the most frequent age interval 15-19 followed by 20-24 years. Twenty-five (26.3%) patients were admitted for their first manic episode, while 23, 13 and 34 patients were admitted for the second, third, and fourth or more illness episodes respectively (Table 1). These 95 cases had a total of 321 lifetime illness episodes of which 283 (88.2%) were manic, and 38 (11.8%) were depressive, The number of manic episodes per person varied from one to 16 (one episode 29, two episodes 27, three 15, four 7, five 2, six 5, seven 6, eight 1, nine 1, twelve 1, sixteen 11 and
the number of depressive episodes varied from one to two (one episode 18, two episodes 10). The mean number of episodes per person was 3.4 + 2.7 (manic 3 + 2.5 and depressive 0.4 rtr0.7). The mean number of siblings per person was 4.95 f 1.87 and the mean birth order 2.76 + 1.9. Among those with a past history of illness (n = 70) the mean duration oi’ illness was 6.3 (k6.5) years, and an episode frequency oL’0.96 ( f 0.53) episode per year. 1;:: first illness episode was manic in 83% of the cases. A biphasic illness was seen in only 11 of these 70 cases (15.7%), There was not a single case with a polyphasic (more than biphasic) illness or with a rapid-cycling affective disorder. Out of the 47 patients with three or more lifetime illness episodes, 30 (64%) showed a sensitisation pattern (subsequent inter-episode intervals shorter than initial intervals).
TABLE 2 COMPARATIVE
DATA ON RECURRENT
MANIA AND TRUE BIPOLARITY
--
Sex (M : F) Age at current hospitalisation (mean k SD) Age at ouset of illness (mean + SD) Years ill (mean f SD) Number of episodes (mean + SD) Total Mania Depression Episodes per year (mean _t SD) Course (sensitisation: non-sensitisation) Number of siblings (mean f SD) Birth order (mean + SD)
Recurrent mania (n = 15)
True bipolarity (n = 19)
Statistical analysis (as appropriate)
12:3 38 511.3 28.3 + 9.1 9.5 * 5
16:3 31.4 f9.3 22.8 f8.8 8.7 k7.8
x2 = - 0.009, NS F = 3.52, NS F = 3.25, NS F-O.ll,NS
7.2 F 3.2 7.2 + 3.2 0 0.91 f 0.5 12:3 5 +1.8 2.5 f 2
5.4 +1.6 3.9 +I.6 1.5 +0.5 0.95 + 0.5 12:7 5.1 f1.6 2.8 k1.3
F = 4.44. P < 0.05 F = 15.42, P C 0.01 F = 0.04, NS x2 = 0.47, NS F = 0.03, NS F = 0.5, NS
38
episode was that of depression and for 16 (57.1%) the first episode was that of mania. Of those who switched from depression to mania, 11 (91.6%) did so in the second episode and one (8.4%) in the third episode. Of those with a first manic episode, for nine (56.3%) the second episode was depressive. For two each the third or fourth episode was that of depression, while the fifth, sixth or seventh episode was the first depressive episode for one patient each. Those patients whose first illness episode was manic had significantly more total illness episodes and, a larger number of manic episodes. All other comparisons were statistically non-significant (Table 3).
Recurrent ,mania 1s. true bipolar
The frequency of episodes in patients with mania only and those with mania and depression is shown in Table 1. The prevalence of recurrent mania in this saniple was high. 60% of the sample (42 out of 70) had two manic episodes without an episode of depression. Among those with three lifetime episodes of illness, 48.9% (23 out of 47) had only manic episodes. Even when unipolar mania was defined as four or more lifetime episodes of mania without any episode of depression, 44% (15 out of 34) fulfilled the criterion. The results of comparison between recurrent mania (defined by the occurrence of four manic episodes without an episode of depression vs. true bipolars) are shown in Table 2. The trend was for the recurrently manic group to be older at the time of the index evaluation and at age of onset. Chi-square evaluation comparing recurrent manics and true bipolars above and below the median age of onset revealed a statistically significant difference between the two groups (x2 = 4.29, P < 0.05). Recurrent manics had significantly more total illness episodes and a larger number of manic episodes compared to true bipolars. All other comparisons were non-significant.
Discussion
One of the most striking features of our sample is the marked prepo,zderance of male subjects (M : F = 80 : 15). Proportionately more females were not included in the study because of a lack of reliable informants (M : F = 9: 8). Again proportionately more females failed to fulfill RDC criteria for definite mania compared to males. Evidence suggests that female schizophrenics at least exhibit more atypical symptoms than male schizophrenics (Lewine, 1981). Further, the triterion for inclusion in our study was a diagnosis of mania at the time of index admission. Perhaps one of the most consistent findings in psychiatric
Switch to the opposite pole
Out of the 28 cases who had a history of both mania and depression, for 12 (42.9%) the first TABLE 3 COMPARATIVE DATA ON PATIENTS WHO SWITCHED SWITCHED FROM MANIA TO DEPRESSION
Sex (M : F)
Age at current hospitalisation (mean + SD) Age at onset of illness (mean i SD) Years ill (mean + SD) Number of episodes (mean + SD) Total Mania Depression Episodes per year (mean + SD) Illness phase tbiphasic: uniphasic) Course (sensitisation: non-sensitisation) Number of siblings (mean + SD) Birth order (mean f SD)
FROM DEPRESSION
TO MANIA AND
THOSE WHO
Depression to mania tn = 12)
(n = 16)
10:2 29.2+ 11.1 21.8k 9.4 7.7* 10.1
12:4 32.8k9.3 25.7+9.5 7.1 -15.8
,$ = 0.004, NS F = 0.86, NS I; = 1.19, NS F = 0.03, NS
5.1+2 3.8+ 1.8 1.3~0.5 0.9+0.4 6: 10 II:5 5.5 + 1,4 2.9+ 1.3
F = 4.56, P < 0.05 F = 6.72, P < 0.05 F = 0.42, NS
3.7, 2.3f 1.4+ 1.2f 4:8 6:6 4.5+ 3 +
1.5 1.1 0.5 0.7
2.2 2.4
Mania to depression
Statistical analysis “C1
F=2,NS
x2 = 0.028, NS x2 = 1.02, NS F = 2.26, NS F = 0.006, NS
39
epidemiology is that women suffer from depression more frequently than men (Weissman and Klerman, 1985). Bland et al. (1988) reported a higher rate of manic episodes for men (0.7%) than women (0.4%). Some male excess has been reported in studies on unipolar mania (Abrams and Taylor, 1974; Nurnberger et al., 1979; Makanjuola, 1985). The sex difference in the admission rates at our institute is approximately four males to one female. The low female admission rate may reflect socio-cultural determinants of hospital admissions. In India, the existing number of mental hospital beds is in the ratio of one bed to approximately 40,000 people. Admission to mental hospitals probably reflects only the incidence of mental illness surpassing the tolerance level of the immediate environment. There is evident. from the literature that males tend to have more severe manias, and a greater number of hospitalisations for mania (Winokur et al., 1969; Angst, 1978; Roy-Byrne et al., 1985). One of the best documented sex differences in human behaviour is a greater tendency for the male to show aggressive behaviour (Ember, 1981). Other socio-cultural factors such as social role assignment and economic compulsions may be important. The female is more likely to be a housekeeper and in the event of illness her role may be more effectively taken over by significant others living within the extended family system. The male is more likely to be the wage-earner and will get immediate attention when his wage-earning capacity is affected. Admission to a psychiatric hospital is often considered a stigma for the patient and his family. In a social context where marriages are largely ‘arranged’ through the social network, a young woman, if hospitalised, may seriously harm her chances of an appropriate matrimonial placement. The mean age of onset of illness was 26.9 ( & 11.3) years, which is in keeping with other hospital-based studies (Nurnberger et al., 1979; Pfohl et al., 1982; Joyce, 1984; Roy-Byrne et al., 1985) but higher than those seen in recent community-based studies (Weissman et al., 1988; Bland et al., 1988). The median age of onset (22 years) was similar to reports in the literature (Winokur et al., 1969: Joyce, 1984; Burke et al.,
1990). The mean age of onset of illness was significantly lower for females. Review of the literature generally suggests chat patients with a later age of onset are predominantly male (Swift, 1907; Kraepelin, 1921; Angst, 1978). Those with recurrent mania had a significantly later age of onset than true bipolars. The mean number of episodes per person was 3.4 f 2.7 (manic 3 + 2.5 and depressive 0.4 f 0.7). While the number of manic episodes per person ranged from one to 16, the number of depressive episodes ranged from one to two only. 60%, 48.9%, and 44% of the cases had two, three and four or more manic episodes without a major depressive episode. Those with recurrent mania (more than four episodes of mania without depression) had significantly more total illness episodes and a larger number of manic episodes than true bipolars. Though the frequency of episodes varies over time and between patients, a review of the literature generally suggests a higher percentage of episodes that are depressive (RoyByrne et al., 1985). Kraepelin (1921) noted that purely depressive and circular insanity were incomparably much more frequent than pure periodic mania. Perris (1982) found only 17 cases of unipolar mania in a sample of 1539 cases. Others (Abrams and Taylor, 1974; Nurnberger et al., 1979; Abrams et al., 1979; Pfohl et al., 1982) have reported higher figures based only on the occurrence of one or two manic episodes without depression. Very few studies have shown an incidence of mania higher than that of depression. In the sample studied by Winokur et al. (1969) the mean number of manic episodes was 2.6 and that of depressive episodes 1.9 per person. Carlsson et al. (1974) reported 3.7 manic and 2.1 depressive episodes per person. Mendlewicz et al. (1972) noted that for patients with a positive family history there were two admissions for mania for every admission for depression. In contrast, among those with no family history there were three admissions for depression for every one for mania. Recent studies, using well defined diagnostic criteria and outcome measures, reveal a higher incidence of recurrent mania. COryell et al. (1989) followed up 53 bipolar I patients over 5 years, during which time 32 (60.4%) had at least
40
one episode of mania or schizoaffective mania, and fewer depressive relapses. Harrow et al. (1990) found 42% of 73 manic patients to have a full manic syndrome, another 13% had some manic symptoms and slightly over 30% had a full depressive syndrome during the follow-up year. In another naturalistic follow-up study of 75 manic patients, Tohen et al. (1990) found manic relapses to far outweigh the depressive. The first illness episode was manic in 83% of our cases. Goodwin and Jamison (1984) on taking an average of numerous studies found that around 50% started the illness with mania. Only uniphasic illness periods were seen in 84.3% of all cases. Even among those with biphasic illness, only two showed such a pattern in more than one illness period. 70% and 60% of the illness periods were reported to be uniphasic by Angst (1978) and Roy-Byrne et al. (1985). Winokur et al. (1969) found that 51% of the manic episodes were preceded and 57% followed by a depressive phase of at least 1 month. In the prospective study by Tohen et al. (1990) only 15% of the patients cycled into depression before recovery to the euthymic state. None of our cases had rapid-cycling affective disorder. This could be because of the low frequency of depressive disorder, or reduced chances of treatment with tricyclics, which is known to precipitate rapid cycling (Wehr and Goodwin, 1987). A switch from depression to mania occurred early: 11 out of 12 (91.7%) switciied at the time of the second episode itself. The switch from mania to depression was more gradual, the first depressive episode was seen as late as after the seventh manic episode. Those who switched from mania to depression had significantly more total illness episodes and a larger number of manic episodes. Perris (1968) and Roy-Byrne et al. (1985) also reported a higher frequency of subsequent manias in patients with a first manic episode. Venkoba-Rao and Nammalvar (197’1)followed up 109 patients in southern India for a period of 3-13 years; 42 of these switched from unipolar to bipolar illness, 64%, 32% and 3% after the first, second, and third episode respectively. Recurrences were more frequent among those who switched to bipolarity and manic episodes were more frequent than depressive episodes.
Our results may be more relevant to hospitalised bipolar patients in developing countries. Hospital admission rates are low and it is probable that only those patients with severe and socially difficult behaviour are hospitalised. This would have the effect of decreasing admission for women and those with depression. Leonhard (1986) has proposed a link between the more common occurrence of mania in developing countries and the presence of relatively many siblings. Too much stimulation in early childhood may create a predisposition which leads to a greater chance of developing mania in later life. In our samp!e the mean number of siblings per index patient was five. The high density of the population, poor housing and consequent overcrowding may increase the chances of overstimulation. Besides, the longitudinal course of bipolar disorder may represent a complex interaction between genetic and environmental factors. The environmental factors may include variables such as season (day length, number of hours of sunshine, air ionisation, ambient temperature and relative humidity), exposure to viruses, diet, etc. The influence of such factors is currently not well understood. Studies conducted in different geographical regions may provide further insight into the possible role of these factors in bipolar disorder. eferences Abrams, R. and Taylor, M.A. (1974) Unipolar mania. Arch. Gen. Psychiatry 30, 441-443. Abrams, R., Taylor, M.A., Hayman, M.A. and Krishna, N.R. (1979) Unipolar mania revisited. J. Affect. Disord. 1, 5968.\ Angst, J. (1978) The course of affective disorders. II. Typology of bipolar manic depressive illness. Arch. Psychiatric Nervenkr. 226, 65-74. Bazzoui, W. (1970) Affective disorders in Iraq. Br. J. Psychiatry 117, 195-203. Belmaker, R.H. and Van Praag, H.M. (1980) Mania: An Evolving Concept. Spectrum, New York, NY. Bland, R.C., Qrn, H. and Newman, SC. (1988) Life time prevalence of psychiatric disorders in Edmonton. Acta Psychiatr. Stand. 77 (Suppl. 338), 24-32. Burke, K.C.. Burke, J.D., Regier, D.A. and Rae, D.S. (1990) Age of onset of selected mental disorders in five community populations. Arch. Gen. Psychiatry 47, 511-518. Carlsson, GA., Kotin, J., Davenport, Y.B. and Adland, M. (1974) Follow up of 53 bipolar manic depressive patients. Br. J. Psychiatry 124, 134-139.
41 Clayton, P.J. (1981) The epidemiology of bipolar affective disorder. Compr. Psychiatry 22, 31-43. Coryell, W., Keller, M., Endicott, J., Andreasen, N., Clayton, P. and Hirschfield, R. (1989) Bipolar II illness: course and outcome over a five year period. Psychol. Med. 19. 129141. Egeland, J.A. (1983) Bipolarity: the iceberg of affective disorders? Compr. Psychiatry 24, 337-344. Ember, C. (1981) A cross-cul!ural perspective on sex difference. In: R. Munroe, R. Munroe and B. Whitney (Eds.), Handbook of Cross Cultural Human Development. Gorland, New York, NY. Endicott, J. and Spitzer, R.L. (1978) A diagnostic interview: the Schedule for Affective Disorders and Schizophrenia. Arch. Gen. Psychiatry 35, 837-844. Gershon, E.S. and Liebowitz, J.H. (1975) Sociocultural and demographic correlation of affective disorders in Jerusalem., J. Psychiatr. Res. ;2, 37-50. Goodwin, F.K. and Jamison. K.R. (1984) The natural course of manic depressive illness. In: R.M. Post and J.C. Ballenger (Eds.), Neurobiology of Mood Disorders. Williams & Wilkins, Baltimore, MD, pp. 20-38. Harrow, M., Goldberg, J.F., Grossman, L.S. and Meltzer, H.Y. (1990) Outcome in manic disorder: a naturalistic follow-up study. Arch. Gen. Psychiatry 47, 665-671. Joyce, P.R. (1984) Age of onset in bipolar affective disorder and misdiagnosis as schizophrenia. Psychol. Med. 14. 145149. Kraepelin, E. (1921) Manic Depressive Insanity and Paranoia. Livingstone. Edinburgh. Leff, J.P., Fischer, M. and Bertelsen, A. (1976) A cross national epidemiological study of mania. Br. J. Psychiatry 129.428-442. Leonhard, E. (1986) Different causative factors in different forms of schizophrenia. Br. J. Psychiatry 149, l-6. Lewine, R.R.J. (1981) Sex differences in schizophrenia: timing or subtypes? Psychol. Bull. 90, 432-444. Makanjuola, R.O.A. (1985) Recurrent unipolar manic disorder in Yoruba Nigerians: further evidence. Br. J. Psychiatry 147,434-432.
Makanjuola, R.O.A. (1989) Sociocultural parameters in Yoruba Nigerian patients with affective disorders. Br. J. Psychiatry 155, 337-340. Mendlewicz, J., Fieve, R.R., Rainer, J.D. and Fleiss, J.L. (1972) Manic depressive illness: a comparative study of patients with and without a family history. Br. J. Psychiatry 120,523-530. Nurnberger, J., Roose, S.P., Dunner, D.L. and Fieve, R.R. (1979) Unipolar mania: a distinct clinical entity? Am. J. Psychiatry 136, 1420-1423. Perris, C. (1968) The course of depressive psychoses. Acta Psychiatr. Stand. 44, 238-248. Perris, C. (1982) The distinction between bipolar and unipolar affective disorders. In: E.S. Paykel (Ed.), Handbook of Affective Disorders. Churchill Livingstone, Edinburgh, pp. 45-68. Pfohl, B., Vesquez, N. and Nasrallah, H. (1982) Unipolar vs. bipolar mania: a review of 247 patients. Br. J. Psychiatry 141, 4538-458. Roy-Byrne, P., Post, R.M. and Uhde, T.W. (1985) The longitudinal course of recurrent affective illness. Acta Psychiatr. Stand. 71 (Suppl. 3171, l-34. Swift, H.M. (1907) The prognosis of recurrent insanity of manic-depressive type. Am. J. Insanity 64, 311-326. Tohen, M., Waternaux, C.M. and Tsuang, M.T. (1990) Outcome in mania. Arch. Gen. Psychiatry 47, 1106-l 111. Venkoba-Rao, A. and Nammalvar, N. (1977) The course and outcome of depressive illness. Br. J. Psychiatry 130, 392396. Wehr, T.A. and Goodwin, F.K. (1987) Can antidepressants cause mania or worsen the course of affective illness? Am. J. Psychiatry 144, 1403-1411. Weissman, M.M. and Klerman, G.L. (1985) Gender and depression. Trends Neurosci. 8, 416-420. Weissman, M.M., Leaf, P.J., Tischler, G.L., Blazer, D.G., Karno, M., Bruce, M.L. and Florio, L.P. (1988) Affective disorders in five United States communities. Psychol. Med. 18, 141-153. Winokur, G., Clayton, P.J. and Reich, T. (1969) Manic Depressive illness. Mosby, St. Louis, MO.
