Journal of Affective Disorders 152-154 (2014) 52–56
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Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad
Review
Unipolar mania: A distinct entity? Olcay Yazıcı n Istanbul University, Istanbul Medical School, Psychiatry Department, Istanbul 34357, Turkey
art ic l e i nf o
a b s t r a c t
Article history: Received 5 June 2013 Received in revised form 14 September 2013 Accepted 2 October 2013 Available online 22 October 2013
Background: Whether or not unipolar mania is a separate nosological entity remains a subject of dispute. This review discusses that question in light of recent data. Methods: Unipolar mania studies in the PUBMED database and relevant publications and crossreferences were searched. Results: There seems to be a bipolar subgroup with a stable, unipolar recurrent manic course, and that 15–20% of bipolar patients may be unipolar manic. Unipolar mania may be more common in females. It seems to have a slightly earlier age of illness onset, more grandiosity, psychotic symptoms, hyperthymic temperament, but less rapid-cycling, suicidality and comorbid anxiety disorders. It seems to have a better course of illness with better social and professional adjustment. However, its response to lithium prophylaxis seems to be worse, although its response to valproate is the same when compared to that of classical bipolar. Limitations: The few studies on the subject are mainly retrospective, and the primary methodological criticism is the uncertainty of the diagnostic criteria for unipolar mania. Conclusions: The results indicate that unipolar mania displays some different clinical characteristics from those of classical bipolar disorder. However, whether or not it is a separate nosological entity has not been determined due to the insufficiency of relevant data. Further studies with standardized diagnostic criteria are needed. Considering unipolar mania as a course specifier of bipolar disorder could be an important step in this respect. & 2013 Elsevier B.V. All rights reserved.
Keywords: Unipolar mania Recurrent mania Bipolar spectrum Manic predominance: Lithium prophylaxis
Contents 1. Introduction . . . . . . . . . . . . . . . . . . 2. Methodology . . . . . . . . . . . . . . . . . 3. The prevalence of unipolar mania 4. Methodological problems . . . . . . . 5. UM as a distinct entity . . . . . . . . . 5. Summary . . . . . . . . . . . . . . . . . . . . 6. Conclusions . . . . . . . . . . . . . . . . . . Role of funding source . . . . . . . . . . . . . Conflict of interest. . . . . . . . . . . . . . . . . Acknowledgment . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction
n
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0165-0327/$ - see front matter & 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jad.2013.10.005
Within the subtypes of bipolar disorders, the existence of a manic disorder with a unipolar course remains a controversial subject. If its existence as a distinct entity were confirmed, then reliable diagnostic criteria could be established, and diagnoses according to those criteria would be stable over time. Once established, those criteria
O. Yazıcı / Journal of Affective Disorders 152-154 (2014) 52–56
Table 1 Is unipolar mania rare?
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.
Leonhard (1957): 9% BD patients Perris (1966): 4.5% BD patients Abrams and Taylor (1974): 28% BD-I patients Abrams et al. (1979): 18% BD patients Nurnberger et al. (1979): 15.7% BD-I patients Perris (1982): 1.1% BD patients Pfohl et al. (1982): 35.2% BD patients (hospitalized) Venkoba Rao and Madhavan (1983): 12% BD patients (onset age 60) Makanjuola (1985): 53% BD-I patients Srinivasan et al. (1985): 40% BD patients (hospitalized) Margoob and Dutta (1988): 42% BD patients Khanna et al. (1992): 44% BD patients (hospitalized) Shulman and Tohen (1994): 12% BD-I patients (hospitalized, age4 65) Avasthi et al. (1996): 6.45% affective disorders patients Aghanwa (2001): 47.2% BD patients Yazıcı et al. (2002): 16.3% BD-I patients Solomon et al. (2003): 26% BD patients Perugi et al. (2007): 21.8% BD-I patients (hospitalized) Dakhlaui et al. (2008): 65.3% BD-I patients Andrade-Nascimento et al. (2011): 5.6% BD-I patients
would be able to help clarify the prevalence of the disorder and be of great help in improving the methodological problems in studies on unipolar mania (UM). According to the current criteria, mania signifies bipolarity; namely, the presence of a manic episode predicts the presence of a depressive episode as well. This, however, can be seen as counterintuitive, since mania and depression are entirely different, more or less opposite syndromes; accordingly, it would have been difficult to first conceive of them as parts of the same illness. Still, as can be seen in the comprehensive review of Angst and Marneros (2001), Aretaeus of Cappadocia (1847) was the first to say that they were two different aspects of the same illness. In 1851, Falret (1851) described an entity that he termed folie circulaire, which was characterized by a continuous cycle of depression, mania, and free interval. With that, he defined the basics of the modern concept of bipolar disorder (BD). Subsequently, came the dichotomization of endogenous psychoses into manic-depressive insanity and dementia praecox by Kraepelin (1899). He was also the first to describe some cases of recurrent manic episodes without depression, which he referred to as periodic mania. Kraepelin's unification grouped all affective disorders (with a unipolar and bipolar course) under one umbrella. In 1900, Wernicke (1990), continuing Falret's concept, claimed that since both mania and depression were mandatory for a diagnosis of manic-depressive insanity, recurrent episodes of singular mania or depression should be viewed as distinct disorders. Similarly, Kleist (1911, 1953) and Leonhard (1957) differentiated between unipolar and bipolar disorders. Whereas pure mania and pure melancholia were classified under the rubric of pure phasic psychoses, manic-depressive illness was classified as a polimorphous phasic psychosis (Leonhard, 1957). Later, Angst (1966) and Perris (1966) showed that unipolar depression was indeed a different entity from BD with respect to various aspects such as gender, genetics, course, premorbid personality, and age of onset, thus confirming the aforementioned assumption for unipolar depression. However, the authors concluded that unipolar mania was related closely, clinically, and genetically to BD, and therefore should be regarded as an artefact of it (Angst and Perris, 1968). This conclusion was accepted univocally, resulting in general quiescence on the subject for the last 50 years, as reflected by the strikingly few number of studies on UM during this time. Another reason for this scarcity of studies could be the assumption that UM is a rare condition.
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2. Methodology The PUBMED database between 1960 and 2013 was searched using the following key words: unipolar mania, recurrent mania, periodic mania, and pure mania. Relevant publications and cross references were searched manually.
3. The prevalence of unipolar mania Leonhard (1957) reported the percentage of UM in BD as 9%. As can be seen in Table 1, this percentage varies between 1.1% and 47.2% in BD patients, 5.6% and 65.3% in Bipolar Disorder I (BD-I) patients, and 35% and 44% in hospitalized BD patients. The variance in these findings may be due to methodological problems or cultural differences.
4. Methodological problems Methodological problems can be divided into three groups: retrospective, present, and prospective errors. Regarding retrospective problems, since a UM diagnosis generally is made retrospectively, some earlier episodes of mild depression may remain unreported or overlooked. In this respect, studies from a specialized mood disorders center, and those using re-interview with the patient and the family about past episodes instead of just a chart review, would increase the reliability of their results. Regarding current errors, the major problem is the lack of consensus on the defining criteria for UM. The basic questions concern the criteria for the minimum number of manic episodes, the minimum duration of follow-up, and criteria for exclusion. Shulman and Tohen (1994), for example, have suggested that at least three manic episodes and a follow-up between 3 and 10 years are needed for a reliable diagnosis of UM. Almost all UM studies base the diagnosis on the absence of a major depressive episode (Table 2). In previous studies, the minimum number of manic episodes was one or two, whereas it has become three or four in more recent ones. These studies generally were carried out utilizing retrospective chart review. There have been two prospective studies with 5 and 20-year follow-up (Makanjuola, 1985; Solomon et al., 2003). In recent studies, a minimum 4 or 5 years of follow-up (Aghanwa, 2001; Yazici et al., 2002; Dakhlaui et al., 2008) or at least 10 years of illness duration (Perugi et al., 2007; Andrade-Nascimento et al., 2011) have been included. Additionally, two studies have emphasized the exclusion of cases with mixed episodes (Yazici et al., 2002; Andrade-Nascimento et al., 2011). In conclusion, a consensus seems to have been reached on the requirement of the presence of at least three or four manic episodes without any intervening depressive episodes for a diagnosis of UM. Currently, a minimum four-year follow-up duration and the exclusion of cases with mixed episodes are being suggested as a diagnostic criterion. However, questions remain about the stability of the diagnosis when these criteria are applied. The main issue with prospective error is the likelihood of depressive episodes that have not been recorded due to insufficient follow-up duration. Therefore, it seems the inclusion of a sufficient time period in the criteria as a required minimum duration of illness or follow-up is important. Still, the fact remains that even in the presence of a long follow-up and any number of manic episodes, the possibility of a future depressive episode cannot be excluded. However, the same criticism and limitations are also valid for a number of disorders, including unipolar depression.
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Table 2 Diagnostic criteria and methods of the unipolar mania studies.
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.
Perris (1966): 0 D, min 1 M, RCR Abrams and Taylor (1974): 0 D, min? M, RCR Abrams et al. (1979): 0 D, min 2 M, RCR Nurnberger et al. (1979): 0 somted for D, min 1 hosp M, RCR þSI in 1/3 of the cases Perris (1982): 0 D, min 1 M, RCR Pfohl et al. (1982): 0 D, min 1 M, RCR Venkoba Rao and Madhavan (1983): 0 D, min? M, RCR Makanjuola (1985): 0 D, min 2 M, prospective follow-up, 5 years Srinivasan et al. (1985): 0 D, min 3 M, RCR, inpatients Margoob and Dutta (1988):? D, min? M, RCR Khanna et al. (1992): 0 D, min 4 M (RDC), RCR, inpatients Shulman and Tohen (1994): 0 D, min 3 M (DSM-III-R), RCR, inpatients, 465 years old Avasthi et al. (1996): 0 D, min 3 M (ICD-10), RCR Aghanwa (2001): 0 D, min 3 M (ICD-10), min 4-year follow-up, RCR Yazıcı et al. (2002): 0 D, min 4 M (DSM-IV), min 4-year follow-up, no Mx, RCR Solomon et al. (2003): 0 D, min 1 M (RDC), prospective follow-up, 15–20 years Perugi et al. (2007): 0 D, min 3 M, (DSM-III-R), min 10-year illness duration, RCR Dakhlaui et al. (2008): 0 D, min 2 M, (DSM-IV), min 5-year follow-up Andrade-Nascimento et al. (2011): 0 D, min? M (DSM-IV), min 15-year illness duration, no Mx, RCR
D: major depression, M: manic episode, Mx: mixed episode, RCR: retrospective chart review, somted: somatic treatment, hosp: hospitalized, SI: structured interview, and min: minimum.
Table 3 How stable is the unipolar mania diagnosis?
1. Abrams and Taylor (1974): follow-up: 10.86 years 2. Abrams et al. (1979): follow-up: 11.7 years 3. Nurnberger et al. (1979): over a 4-month follow-up, 29% of patients converted to BD 4. Perris (1982): change in polarity is mainly by the 3rd episode, rare after the 8th episode 5. Makanjuola (1985): follow-up: 5.9 years 6. Srinivasan et al. (1985): follow-up: 12 years 7. Khanna et al. (1992): follow-up: 9.5 years 8. Shulman and Tohen (1994): follow-up: 27.7 years, no change in polarity 9. Avasthi et al. (1996): follow-up: 7 years 10. Aghanwa (2001): follow-up: 16.6 years 11. Yazıcı et al. (2002): follow-up: 12 years 12. Solomon et al. (2003): prospective follow-up: 20 years, 25.9% were still UM 13. Yazıcı et al. (2008): prospective follow-up: 7 years, 88.2% were still UM
Among the studies, the duration of follow-up varies between 6 and 28 years (Table 3). Nurnberger et al. (1979) reported that over a 4-month follow-up, one-third of the cases were rediagnosed as BD; however, in some cases this was partly because of additional information about earlier episodes. Perris (1982) observed that change in polarity mainly occurred by the third episode, and that this probability was rare after the eighth episode. On the other hand, two studies with follow-ups as long as 20 and 28 years reported no change in polarity in either case (Shulman and Tohen, 1994) or at least in 26% of the cases (Solomon et al., 2003). This controversy may be related to the diagnostic criteria used. Yazici et al. (unpublished data) investigated the probability of conversion from UM to BD using the Kaplan–Meier Survival Analysis in 272 patients diagnosed as BD according to the DSMIV. The results suggested that the longer the follow-up period and
the greater the number of manic episodes, the lower the probability the UM diagnosis would be “false”. When an optimal cut-off point was sought, it was found that for cases with at least four manic episodes and at least a four-year follow-up, the probability of UM remaining stable for the following at least nine years was 88.4%. A study according to these criteria revealed that 48 of the 272, namely 16.3% of the BD-I patients, were UM (Yazici et al., 2002). After a 7-year prospective follow-up, 34 of these patients were still being followed, and 30, that is 88.2%, of them were still UM (Yazici et al., 2008). These data seem to confirm the existence of a BD group with a stable UM course. However, how different they are from subjects diagnosed with classical BD, and whether UM can be seen as a distinct nosological entity remains unknown.
5. UM as a distinct entity Focusing on the findings that suggest some differences between UM and BD, four studies reported that the onset age of illness was slightly earlier in UM (Taylor and Abrams, 1973; Shulman and Tohen, 1994; Yazici et al., 2002; Dakhlaui et al., 2008), whereas other studies found no significant differences in this respect. Regarding gender, some early studies reported a male preponderence in UM (Abrams et al., 1979; Kubacki, 1986), whereas others found no difference in this respect (Nurnberger et al., 1979; Pfohl et al., 1982; Makanjuola, 1985; Khanna et al., 1992). In more recent studies, however, UM was found to be more common in females (Aghanwa, 2001; Yazici et al., 2002; Solomon et al., 2003). The majority of studies on UM have come from “non-Western” countries, such as Nigeria (Makanjuola, 1985), India (Khanna et al., 1992; Avasthi et al., 1996), the Fiji Islands (Aghanwa, 2001), Turkey (Yazici et al., 2002), Hong Kong (Lee and Yu, 1994), and Tunisia (Dakhlaui et al., 2008; Douki et al., 2012). This raises the question of whether UM is more common in those countries. Although in one study, the percentage of UM was rather low, 16% of the BD-I patients (Yazici et al., 2002), in contrast, this figure was 53% (Makanjuola, 1985), in the other two studies from non-western countries, and 65% (Dakhlaui et al., 2008). Additionally, it was stated in one of these studies that “unipolar manic course is almost the rule rather than the exception in Nigeria” (Makanjuola, 1985). This contradiction may be related to methodological differences. However, a recent cross-cultural study reported that UM was three times more common in Tunisia than in France (Douki et al., 2012). In the two studies from the US, the majority of the UM patients came from Iowa (Pfohl et al., 1982; Solomon et al., 2003), which was described as being a more rural setting than the other regions studied (Solomon et al., 2003). The terms “a rural setting” or “nonWestern culture” may be conceived as being “less developed” (Harish et al., 2005). However, conceptualizing the relationship between “being less developed” and “being unipolar manic” may be difficult. As Harish et al. (2005) said, “it needs to be seen whether culture has any role in UM's prevalence, and, if so, in what way”. Considering that BD is a biological or genetic disorder, the possible differences in different cultures in this respect could be related to ethnic characteristics. However, the only study comparing the prevalence of UM among different ethnic groups, carried out in Fiji, found no significant differences in this regard (Aghanwa, 2001). Similarly, the ratios of white/black (Abrams et al., 1979) or Caucasian/other patients (Pfohl et al., 1982) were not different in UM and BP groups. Environmental factors that may have a role in clinical presentation such as psychosocial variables, exposure to viruses, diet and prenatal environment
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(Pfohl et al., 1982) also should be taken into consideration in future studies. Cross-cultural studies would benefit from further investigation using stricter criteria for UM. Studies on clinical features have revealed that the following characteristics appear to be more prevalent in UM than in classic BD: grandiosity (Abrams et al., 1979; Pfohl et al., 1982), psychotic episodes (Pfohl et al., 1982) or symptoms (Yazici et al., 2002), psychotic first episode (Yazici et al., 2002; Andrade-Nascimento et al., 2011), congruent psychotic symptoms (Pfohl et al., 1982; Perugi et al., 2007), and hyperthymic temperament (Leonhard, 1963; Yazici et al., 2002; Perugi et al., 2007); whereas rapid-cycling and suicidality (Nurnberger et al., 1979; Yazici et al., 2002), and comorbid anxiety disorders (Andrade-Nascimento et al., 2011) were less common in UM. Additionally, UM had better social adjustment and less disability in the course of illness (Andrade-Nascimento et al., 2011). In terms of family history, Abrams et al. (1979) reported an increased risk of unipolar depression in the first-degree relatives of people diagnosed with UM. Yazici et al. (2002) found that the UM group had a remarkable tendency to have less unipolar depression and absence of suicide among first-degree relatives. However, the differences failed to reach a statistical significance. Aghanwa (2001) reported that family history of affective illness was lower in UM than in BD. Some other studies reported no differences in terms of major psychiatric morbidity and family histories between UM and BD (Nurnberger et al., 1979; Dakhlaui et al., 2008). Neuroimaging revealed that UM patients had smaller thirdventricular width (Mukherjee et al., 1992); and after brain injury, they had smaller subcortical, but larger cortical lesions, than classical BD patients (Starkstein et al., 1991). Parallel to these findings, in one study, UM patients had less thyroid autoimmunity during chronic lithium treatment (Lee et al., 1992), and in another, higher mini-mental scores after brain injury compared to classic BD (Starkstein et al., 1991). However, Çakir et al. (2008) found no differences in terms of neuropsychological tests between euthymic UM and BD patients. Perhaps the most important finding in support of the view that UM is an entity distinct from BD is the difference in treatment response characteristics. Although no such difference has been reported with respect to the acute treatment of mania, different response characteristics to prophylactic treatment have been reported. Nurnberger et al. (1979) reported that response to lithium prophylaxis was similar in patients with UM and BD patients who had been hospitalized for depression; however, lithium was less effective in BD patients who had never been hospitalized for depression. That finding may suggest that the predominance of depression in BD patients may be associated with a better response to lithium maintenance. Response in UM thus could be predicted to be poorer than that in classical BD patients. Yazici et al. (2002) also observed that the response to lithium prophylaxis was similar in patients with UM and BD when the response modes were categorized as good, moderate, and poor; however, when the patients were divided into responders and non-responders, combining the good and moderate groups as responders, the UM group had significantly fewer responders. This result supports the notion that UM may be a distinct nosological entity. On the other hand, Angst et al. (2004) showed that BD-I is a heterogenous entity. The “manic” (M/Md) group, namely, UM and BD-I patients with a marked preponderance of manic episodes during the course of illness, appeared to differ from the “classical bipolar” (MD) group in terms of some characteristics in that they had a lower risk of recurrence, chronicity, and suicide, better academic achievement, and longer duration of euthymia with or without maintenance treatment. These data raise the question of whether the differences between UM and classical BD emerge because UM is a distinct
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entity or because the predominance of mania exceeds a particular point. In a study covering 34 UM and 87 classical BD-I patients, Yazici and Cakir (2012) found that the response rate to lithium prophylaxis was significantly less in the UM group than that in the BD group (54% versus 83%, p ¼0.004), whereas the response rate to valproate prophylaxis was similar in both groups (95% in the UM group and 93% in the BD group). These data suggest that valproate may be a better choice for prophylactic treatment in UM patients. Secondly, when the difference in the response to lithium prophylaxis was investigated, comparison of all the bipolar patients (UM and BD groups together) with a manic episode rate of o50% and 450%, and o80% and 480% showed that the response rates were lower in the patients with manic preponderance and that the difference increased as the degree of preponderance increased; however, there was no difference when the UM group was excluded from the comparisons. These findings indicate that being less responsive to lithium prophylaxis was associated more closely with UM than with manic preponderance in bipolarity.
5. Summary The available data suggest that there is a BD subgroup with a stable unipolar recurrent manic course, and that 15–20% of BD patients may be UM. The different prevalence rates of this subtype in different countries or cultures present a topic to be investigated. The main obstacles to interpreting the UM data are the uncertainty of the diagnostic criteria for UM, and the scarcity of studies on this subject. Still, having at least four manic episodes and a minimum four-year follow-up seem to be reliable diagnostic criteria for future studies. Despite the limitations of the methodological problems and the differences, the data may still allow us to describe this subtype as such: UM may be more common in females. It seems to have a slightly earlier age of illness onset, as well as more grandiosity, psychotic symptoms, and hyperthymic temperament, but fewer rapid-cycling, suicidality and comorbid anxiety disorders. Despite the two characteristics, being manic and more psychotic, probably leading to more hospitalizations, it seems to have a better course of illness with a more social and work adjustment, and less disability. On the other hand, its response to lithium prophylaxis seems to be lower, whereas it is the same when compared to classical BD in terms of response to valproate.
6. Conclusions Although the available data on UM do not warrant its classification as a separate nosological entity, the notion of UM has importance both in clinical and biological aspects. We need more such studies with standardized diagnostic criteria and crosscultural settings to clarify the issue. In this respect, the addition of UM as a longitudinal course specifier of BD in the diagnostic systems could be a crucial step.
Role of funding source The author of this paper has no funding source to report.
Conflict of interest The author of this paper has no conflicts of interest to report.
Acknowledgment I thank Ms. Kathyryn Kranzler and Mr. Hakan Gurvit, who kindly corrected the English expression of the paper.
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Lee, S., Yu, H., 1994. Unipolar mania in non-western cultures (letter). Br. J. Psychiatry 165, 413. Lee, S., Chow, C.C., Wing, Y.K., Shek, C.C., 1992. Thyroid abnormalities during chronic lithium treatment in Hong Kong Chinese: a controlled study. J. Affect. Disord. 26, 173–178. Leonhard, K., 1957. Aufteilung der endogenen psychosen und ihre differenzierte atiologie. Akademie-Verlag, Berlin. Leonhard, K., 1963. Die temperamente in den familien der monopolaren euphorischen psychosen. Psychiatr. Neurol. Med. Psychol. 15, 203–207. Makanjuola, R.O.A., 1985. Recurrent unipolar manic disorder in the Yoruba Nigerian: further evidence. Br. J. Psychiatry 147, 434–437. Margoob, M.A., Dutta, K.S., 1988. A 15-years retrospective study of 50 patients of MDP for seasonal variations. Indian J. Psychiatry 30, 253–256. Mukherjee, S., Scnur, D.B., Reddy, R., 1992. Unipolar mania reconsidered: a CT scan study. Biol. Psychiatry 31, 248A. Nurnberger, J., Roose, S.P., Dunner, D.L., Fieve, R.R., 1979. Unipolar mania: a distinct clinical entity? Am. J. Psychiatry 136, 1420–1423. Perris, C., 1966. A study of bipolar (manic-depressive) and unipolar recurrent depressive psychoses. Acta Psychiatr. Scand. 194 (Suppl), 1–89. Perris, C., 1982. The distiction between bipolar and unipolar affective disorders. In: Paykel, E.S. (Ed.), Handbook of Affective Disorders. Churchill Livingstone, London, pp. 45–68. Perugi, G., Passino, M.C., Toni, C., Maremmani, I., Angst, J., 2007. Is unipolar mania a distinct subtype? Compr. Psychiatry 48, 213–217. Pfohl, B., Vasquez, N., Nasrallah, H., 1982. Unipolar vs. bipolar mania: a review of 247 patients. Br. J. Psychiatry 141, 453–458. Shulman, K.I., Tohen, M., 1994. Unipolar mania reconsidered: evidence from an elderly cohort. Br. J. Psychiatry 164, 547–549. Solomon, D.A., Leon, A.C., Endicott, J., Coryell, W.H., Mueller, T.I., Posternak, M.A., Keller, M.B., 2003. Unipolar mania over the course of a 20-year follow-up study. Am. J. Psychiatry 160, 2049–2051. Srinivasan, K., Ray, R., Gopinath, P.S., 1985. Unipolar mania – a separate entity? Indian J. Psychiatry 27, 321–324. Starkstein, S.E., Federoff, P., Berthier, M.L., Robinson, R.G., 1991. Manic-depressive and pure manic states after brain lesions. Biol. Psychiatry 29, 149–158. Taylor, M.A., Abrams, R., 1973. Manic states: a genetic study of early and late onset affective disorders. Arch. Gen. Psychiatry 28, 656–658. Venkoba Rao, A., Madhavan, T., 1983. Depression and suicide behavior in the aged. Indian J. Psychiatry 25, 251–259. Wernicke, C., 1900. Grundriss der psychiatrie. Leipzig Thieme. Yazici, O., Kora, K., Ucok, A., Saylan, M., Özdemir, Ö., Kiziltan, E., Özpulat, T., 2002. Unipolar mania: a distinct disorder? J. Affect. Disord. 71, 97–103. Yazici, O., Cakir, S., Kora, K., 2008. Validity of unipolar mania diagnosis. Bipolar Disord. 10 (Suppl), 66. Yazici, O., Cakir, S., 2012. Unipolar mania: a distinct entity or characteristic of manic preponderance? Turk. Psikiyatri Dergisi 23, 201–205.
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Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad
Review
Unipolar mania: A distinct entity? Olcay Yazıcı n Istanbul University, Istanbul Medical School, Psychiatry Department, Istanbul 34357, Turkey
art ic l e i nf o
a b s t r a c t
Article history: Received 5 June 2013 Received in revised form 14 September 2013 Accepted 2 October 2013 Available online 22 October 2013
Background: Whether or not unipolar mania is a separate nosological entity remains a subject of dispute. This review discusses that question in light of recent data. Methods: Unipolar mania studies in the PUBMED database and relevant publications and crossreferences were searched. Results: There seems to be a bipolar subgroup with a stable, unipolar recurrent manic course, and that 15–20% of bipolar patients may be unipolar manic. Unipolar mania may be more common in females. It seems to have a slightly earlier age of illness onset, more grandiosity, psychotic symptoms, hyperthymic temperament, but less rapid-cycling, suicidality and comorbid anxiety disorders. It seems to have a better course of illness with better social and professional adjustment. However, its response to lithium prophylaxis seems to be worse, although its response to valproate is the same when compared to that of classical bipolar. Limitations: The few studies on the subject are mainly retrospective, and the primary methodological criticism is the uncertainty of the diagnostic criteria for unipolar mania. Conclusions: The results indicate that unipolar mania displays some different clinical characteristics from those of classical bipolar disorder. However, whether or not it is a separate nosological entity has not been determined due to the insufficiency of relevant data. Further studies with standardized diagnostic criteria are needed. Considering unipolar mania as a course specifier of bipolar disorder could be an important step in this respect. & 2013 Elsevier B.V. All rights reserved.
Keywords: Unipolar mania Recurrent mania Bipolar spectrum Manic predominance: Lithium prophylaxis
Contents 1. Introduction . . . . . . . . . . . . . . . . . . 2. Methodology . . . . . . . . . . . . . . . . . 3. The prevalence of unipolar mania 4. Methodological problems . . . . . . . 5. UM as a distinct entity . . . . . . . . . 5. Summary . . . . . . . . . . . . . . . . . . . . 6. Conclusions . . . . . . . . . . . . . . . . . . Role of funding source . . . . . . . . . . . . . Conflict of interest. . . . . . . . . . . . . . . . . Acknowledgment . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction
n
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0165-0327/$ - see front matter & 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jad.2013.10.005
Within the subtypes of bipolar disorders, the existence of a manic disorder with a unipolar course remains a controversial subject. If its existence as a distinct entity were confirmed, then reliable diagnostic criteria could be established, and diagnoses according to those criteria would be stable over time. Once established, those criteria
O. Yazıcı / Journal of Affective Disorders 152-154 (2014) 52–56
Table 1 Is unipolar mania rare?
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.
Leonhard (1957): 9% BD patients Perris (1966): 4.5% BD patients Abrams and Taylor (1974): 28% BD-I patients Abrams et al. (1979): 18% BD patients Nurnberger et al. (1979): 15.7% BD-I patients Perris (1982): 1.1% BD patients Pfohl et al. (1982): 35.2% BD patients (hospitalized) Venkoba Rao and Madhavan (1983): 12% BD patients (onset age 60) Makanjuola (1985): 53% BD-I patients Srinivasan et al. (1985): 40% BD patients (hospitalized) Margoob and Dutta (1988): 42% BD patients Khanna et al. (1992): 44% BD patients (hospitalized) Shulman and Tohen (1994): 12% BD-I patients (hospitalized, age4 65) Avasthi et al. (1996): 6.45% affective disorders patients Aghanwa (2001): 47.2% BD patients Yazıcı et al. (2002): 16.3% BD-I patients Solomon et al. (2003): 26% BD patients Perugi et al. (2007): 21.8% BD-I patients (hospitalized) Dakhlaui et al. (2008): 65.3% BD-I patients Andrade-Nascimento et al. (2011): 5.6% BD-I patients
would be able to help clarify the prevalence of the disorder and be of great help in improving the methodological problems in studies on unipolar mania (UM). According to the current criteria, mania signifies bipolarity; namely, the presence of a manic episode predicts the presence of a depressive episode as well. This, however, can be seen as counterintuitive, since mania and depression are entirely different, more or less opposite syndromes; accordingly, it would have been difficult to first conceive of them as parts of the same illness. Still, as can be seen in the comprehensive review of Angst and Marneros (2001), Aretaeus of Cappadocia (1847) was the first to say that they were two different aspects of the same illness. In 1851, Falret (1851) described an entity that he termed folie circulaire, which was characterized by a continuous cycle of depression, mania, and free interval. With that, he defined the basics of the modern concept of bipolar disorder (BD). Subsequently, came the dichotomization of endogenous psychoses into manic-depressive insanity and dementia praecox by Kraepelin (1899). He was also the first to describe some cases of recurrent manic episodes without depression, which he referred to as periodic mania. Kraepelin's unification grouped all affective disorders (with a unipolar and bipolar course) under one umbrella. In 1900, Wernicke (1990), continuing Falret's concept, claimed that since both mania and depression were mandatory for a diagnosis of manic-depressive insanity, recurrent episodes of singular mania or depression should be viewed as distinct disorders. Similarly, Kleist (1911, 1953) and Leonhard (1957) differentiated between unipolar and bipolar disorders. Whereas pure mania and pure melancholia were classified under the rubric of pure phasic psychoses, manic-depressive illness was classified as a polimorphous phasic psychosis (Leonhard, 1957). Later, Angst (1966) and Perris (1966) showed that unipolar depression was indeed a different entity from BD with respect to various aspects such as gender, genetics, course, premorbid personality, and age of onset, thus confirming the aforementioned assumption for unipolar depression. However, the authors concluded that unipolar mania was related closely, clinically, and genetically to BD, and therefore should be regarded as an artefact of it (Angst and Perris, 1968). This conclusion was accepted univocally, resulting in general quiescence on the subject for the last 50 years, as reflected by the strikingly few number of studies on UM during this time. Another reason for this scarcity of studies could be the assumption that UM is a rare condition.
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2. Methodology The PUBMED database between 1960 and 2013 was searched using the following key words: unipolar mania, recurrent mania, periodic mania, and pure mania. Relevant publications and cross references were searched manually.
3. The prevalence of unipolar mania Leonhard (1957) reported the percentage of UM in BD as 9%. As can be seen in Table 1, this percentage varies between 1.1% and 47.2% in BD patients, 5.6% and 65.3% in Bipolar Disorder I (BD-I) patients, and 35% and 44% in hospitalized BD patients. The variance in these findings may be due to methodological problems or cultural differences.
4. Methodological problems Methodological problems can be divided into three groups: retrospective, present, and prospective errors. Regarding retrospective problems, since a UM diagnosis generally is made retrospectively, some earlier episodes of mild depression may remain unreported or overlooked. In this respect, studies from a specialized mood disorders center, and those using re-interview with the patient and the family about past episodes instead of just a chart review, would increase the reliability of their results. Regarding current errors, the major problem is the lack of consensus on the defining criteria for UM. The basic questions concern the criteria for the minimum number of manic episodes, the minimum duration of follow-up, and criteria for exclusion. Shulman and Tohen (1994), for example, have suggested that at least three manic episodes and a follow-up between 3 and 10 years are needed for a reliable diagnosis of UM. Almost all UM studies base the diagnosis on the absence of a major depressive episode (Table 2). In previous studies, the minimum number of manic episodes was one or two, whereas it has become three or four in more recent ones. These studies generally were carried out utilizing retrospective chart review. There have been two prospective studies with 5 and 20-year follow-up (Makanjuola, 1985; Solomon et al., 2003). In recent studies, a minimum 4 or 5 years of follow-up (Aghanwa, 2001; Yazici et al., 2002; Dakhlaui et al., 2008) or at least 10 years of illness duration (Perugi et al., 2007; Andrade-Nascimento et al., 2011) have been included. Additionally, two studies have emphasized the exclusion of cases with mixed episodes (Yazici et al., 2002; Andrade-Nascimento et al., 2011). In conclusion, a consensus seems to have been reached on the requirement of the presence of at least three or four manic episodes without any intervening depressive episodes for a diagnosis of UM. Currently, a minimum four-year follow-up duration and the exclusion of cases with mixed episodes are being suggested as a diagnostic criterion. However, questions remain about the stability of the diagnosis when these criteria are applied. The main issue with prospective error is the likelihood of depressive episodes that have not been recorded due to insufficient follow-up duration. Therefore, it seems the inclusion of a sufficient time period in the criteria as a required minimum duration of illness or follow-up is important. Still, the fact remains that even in the presence of a long follow-up and any number of manic episodes, the possibility of a future depressive episode cannot be excluded. However, the same criticism and limitations are also valid for a number of disorders, including unipolar depression.
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Table 2 Diagnostic criteria and methods of the unipolar mania studies.
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.
Perris (1966): 0 D, min 1 M, RCR Abrams and Taylor (1974): 0 D, min? M, RCR Abrams et al. (1979): 0 D, min 2 M, RCR Nurnberger et al. (1979): 0 somted for D, min 1 hosp M, RCR þSI in 1/3 of the cases Perris (1982): 0 D, min 1 M, RCR Pfohl et al. (1982): 0 D, min 1 M, RCR Venkoba Rao and Madhavan (1983): 0 D, min? M, RCR Makanjuola (1985): 0 D, min 2 M, prospective follow-up, 5 years Srinivasan et al. (1985): 0 D, min 3 M, RCR, inpatients Margoob and Dutta (1988):? D, min? M, RCR Khanna et al. (1992): 0 D, min 4 M (RDC), RCR, inpatients Shulman and Tohen (1994): 0 D, min 3 M (DSM-III-R), RCR, inpatients, 465 years old Avasthi et al. (1996): 0 D, min 3 M (ICD-10), RCR Aghanwa (2001): 0 D, min 3 M (ICD-10), min 4-year follow-up, RCR Yazıcı et al. (2002): 0 D, min 4 M (DSM-IV), min 4-year follow-up, no Mx, RCR Solomon et al. (2003): 0 D, min 1 M (RDC), prospective follow-up, 15–20 years Perugi et al. (2007): 0 D, min 3 M, (DSM-III-R), min 10-year illness duration, RCR Dakhlaui et al. (2008): 0 D, min 2 M, (DSM-IV), min 5-year follow-up Andrade-Nascimento et al. (2011): 0 D, min? M (DSM-IV), min 15-year illness duration, no Mx, RCR
D: major depression, M: manic episode, Mx: mixed episode, RCR: retrospective chart review, somted: somatic treatment, hosp: hospitalized, SI: structured interview, and min: minimum.
Table 3 How stable is the unipolar mania diagnosis?
1. Abrams and Taylor (1974): follow-up: 10.86 years 2. Abrams et al. (1979): follow-up: 11.7 years 3. Nurnberger et al. (1979): over a 4-month follow-up, 29% of patients converted to BD 4. Perris (1982): change in polarity is mainly by the 3rd episode, rare after the 8th episode 5. Makanjuola (1985): follow-up: 5.9 years 6. Srinivasan et al. (1985): follow-up: 12 years 7. Khanna et al. (1992): follow-up: 9.5 years 8. Shulman and Tohen (1994): follow-up: 27.7 years, no change in polarity 9. Avasthi et al. (1996): follow-up: 7 years 10. Aghanwa (2001): follow-up: 16.6 years 11. Yazıcı et al. (2002): follow-up: 12 years 12. Solomon et al. (2003): prospective follow-up: 20 years, 25.9% were still UM 13. Yazıcı et al. (2008): prospective follow-up: 7 years, 88.2% were still UM
Among the studies, the duration of follow-up varies between 6 and 28 years (Table 3). Nurnberger et al. (1979) reported that over a 4-month follow-up, one-third of the cases were rediagnosed as BD; however, in some cases this was partly because of additional information about earlier episodes. Perris (1982) observed that change in polarity mainly occurred by the third episode, and that this probability was rare after the eighth episode. On the other hand, two studies with follow-ups as long as 20 and 28 years reported no change in polarity in either case (Shulman and Tohen, 1994) or at least in 26% of the cases (Solomon et al., 2003). This controversy may be related to the diagnostic criteria used. Yazici et al. (unpublished data) investigated the probability of conversion from UM to BD using the Kaplan–Meier Survival Analysis in 272 patients diagnosed as BD according to the DSMIV. The results suggested that the longer the follow-up period and
the greater the number of manic episodes, the lower the probability the UM diagnosis would be “false”. When an optimal cut-off point was sought, it was found that for cases with at least four manic episodes and at least a four-year follow-up, the probability of UM remaining stable for the following at least nine years was 88.4%. A study according to these criteria revealed that 48 of the 272, namely 16.3% of the BD-I patients, were UM (Yazici et al., 2002). After a 7-year prospective follow-up, 34 of these patients were still being followed, and 30, that is 88.2%, of them were still UM (Yazici et al., 2008). These data seem to confirm the existence of a BD group with a stable UM course. However, how different they are from subjects diagnosed with classical BD, and whether UM can be seen as a distinct nosological entity remains unknown.
5. UM as a distinct entity Focusing on the findings that suggest some differences between UM and BD, four studies reported that the onset age of illness was slightly earlier in UM (Taylor and Abrams, 1973; Shulman and Tohen, 1994; Yazici et al., 2002; Dakhlaui et al., 2008), whereas other studies found no significant differences in this respect. Regarding gender, some early studies reported a male preponderence in UM (Abrams et al., 1979; Kubacki, 1986), whereas others found no difference in this respect (Nurnberger et al., 1979; Pfohl et al., 1982; Makanjuola, 1985; Khanna et al., 1992). In more recent studies, however, UM was found to be more common in females (Aghanwa, 2001; Yazici et al., 2002; Solomon et al., 2003). The majority of studies on UM have come from “non-Western” countries, such as Nigeria (Makanjuola, 1985), India (Khanna et al., 1992; Avasthi et al., 1996), the Fiji Islands (Aghanwa, 2001), Turkey (Yazici et al., 2002), Hong Kong (Lee and Yu, 1994), and Tunisia (Dakhlaui et al., 2008; Douki et al., 2012). This raises the question of whether UM is more common in those countries. Although in one study, the percentage of UM was rather low, 16% of the BD-I patients (Yazici et al., 2002), in contrast, this figure was 53% (Makanjuola, 1985), in the other two studies from non-western countries, and 65% (Dakhlaui et al., 2008). Additionally, it was stated in one of these studies that “unipolar manic course is almost the rule rather than the exception in Nigeria” (Makanjuola, 1985). This contradiction may be related to methodological differences. However, a recent cross-cultural study reported that UM was three times more common in Tunisia than in France (Douki et al., 2012). In the two studies from the US, the majority of the UM patients came from Iowa (Pfohl et al., 1982; Solomon et al., 2003), which was described as being a more rural setting than the other regions studied (Solomon et al., 2003). The terms “a rural setting” or “nonWestern culture” may be conceived as being “less developed” (Harish et al., 2005). However, conceptualizing the relationship between “being less developed” and “being unipolar manic” may be difficult. As Harish et al. (2005) said, “it needs to be seen whether culture has any role in UM's prevalence, and, if so, in what way”. Considering that BD is a biological or genetic disorder, the possible differences in different cultures in this respect could be related to ethnic characteristics. However, the only study comparing the prevalence of UM among different ethnic groups, carried out in Fiji, found no significant differences in this regard (Aghanwa, 2001). Similarly, the ratios of white/black (Abrams et al., 1979) or Caucasian/other patients (Pfohl et al., 1982) were not different in UM and BP groups. Environmental factors that may have a role in clinical presentation such as psychosocial variables, exposure to viruses, diet and prenatal environment
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(Pfohl et al., 1982) also should be taken into consideration in future studies. Cross-cultural studies would benefit from further investigation using stricter criteria for UM. Studies on clinical features have revealed that the following characteristics appear to be more prevalent in UM than in classic BD: grandiosity (Abrams et al., 1979; Pfohl et al., 1982), psychotic episodes (Pfohl et al., 1982) or symptoms (Yazici et al., 2002), psychotic first episode (Yazici et al., 2002; Andrade-Nascimento et al., 2011), congruent psychotic symptoms (Pfohl et al., 1982; Perugi et al., 2007), and hyperthymic temperament (Leonhard, 1963; Yazici et al., 2002; Perugi et al., 2007); whereas rapid-cycling and suicidality (Nurnberger et al., 1979; Yazici et al., 2002), and comorbid anxiety disorders (Andrade-Nascimento et al., 2011) were less common in UM. Additionally, UM had better social adjustment and less disability in the course of illness (Andrade-Nascimento et al., 2011). In terms of family history, Abrams et al. (1979) reported an increased risk of unipolar depression in the first-degree relatives of people diagnosed with UM. Yazici et al. (2002) found that the UM group had a remarkable tendency to have less unipolar depression and absence of suicide among first-degree relatives. However, the differences failed to reach a statistical significance. Aghanwa (2001) reported that family history of affective illness was lower in UM than in BD. Some other studies reported no differences in terms of major psychiatric morbidity and family histories between UM and BD (Nurnberger et al., 1979; Dakhlaui et al., 2008). Neuroimaging revealed that UM patients had smaller thirdventricular width (Mukherjee et al., 1992); and after brain injury, they had smaller subcortical, but larger cortical lesions, than classical BD patients (Starkstein et al., 1991). Parallel to these findings, in one study, UM patients had less thyroid autoimmunity during chronic lithium treatment (Lee et al., 1992), and in another, higher mini-mental scores after brain injury compared to classic BD (Starkstein et al., 1991). However, Çakir et al. (2008) found no differences in terms of neuropsychological tests between euthymic UM and BD patients. Perhaps the most important finding in support of the view that UM is an entity distinct from BD is the difference in treatment response characteristics. Although no such difference has been reported with respect to the acute treatment of mania, different response characteristics to prophylactic treatment have been reported. Nurnberger et al. (1979) reported that response to lithium prophylaxis was similar in patients with UM and BD patients who had been hospitalized for depression; however, lithium was less effective in BD patients who had never been hospitalized for depression. That finding may suggest that the predominance of depression in BD patients may be associated with a better response to lithium maintenance. Response in UM thus could be predicted to be poorer than that in classical BD patients. Yazici et al. (2002) also observed that the response to lithium prophylaxis was similar in patients with UM and BD when the response modes were categorized as good, moderate, and poor; however, when the patients were divided into responders and non-responders, combining the good and moderate groups as responders, the UM group had significantly fewer responders. This result supports the notion that UM may be a distinct nosological entity. On the other hand, Angst et al. (2004) showed that BD-I is a heterogenous entity. The “manic” (M/Md) group, namely, UM and BD-I patients with a marked preponderance of manic episodes during the course of illness, appeared to differ from the “classical bipolar” (MD) group in terms of some characteristics in that they had a lower risk of recurrence, chronicity, and suicide, better academic achievement, and longer duration of euthymia with or without maintenance treatment. These data raise the question of whether the differences between UM and classical BD emerge because UM is a distinct
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entity or because the predominance of mania exceeds a particular point. In a study covering 34 UM and 87 classical BD-I patients, Yazici and Cakir (2012) found that the response rate to lithium prophylaxis was significantly less in the UM group than that in the BD group (54% versus 83%, p ¼0.004), whereas the response rate to valproate prophylaxis was similar in both groups (95% in the UM group and 93% in the BD group). These data suggest that valproate may be a better choice for prophylactic treatment in UM patients. Secondly, when the difference in the response to lithium prophylaxis was investigated, comparison of all the bipolar patients (UM and BD groups together) with a manic episode rate of o50% and 450%, and o80% and 480% showed that the response rates were lower in the patients with manic preponderance and that the difference increased as the degree of preponderance increased; however, there was no difference when the UM group was excluded from the comparisons. These findings indicate that being less responsive to lithium prophylaxis was associated more closely with UM than with manic preponderance in bipolarity.
5. Summary The available data suggest that there is a BD subgroup with a stable unipolar recurrent manic course, and that 15–20% of BD patients may be UM. The different prevalence rates of this subtype in different countries or cultures present a topic to be investigated. The main obstacles to interpreting the UM data are the uncertainty of the diagnostic criteria for UM, and the scarcity of studies on this subject. Still, having at least four manic episodes and a minimum four-year follow-up seem to be reliable diagnostic criteria for future studies. Despite the limitations of the methodological problems and the differences, the data may still allow us to describe this subtype as such: UM may be more common in females. It seems to have a slightly earlier age of illness onset, as well as more grandiosity, psychotic symptoms, and hyperthymic temperament, but fewer rapid-cycling, suicidality and comorbid anxiety disorders. Despite the two characteristics, being manic and more psychotic, probably leading to more hospitalizations, it seems to have a better course of illness with a more social and work adjustment, and less disability. On the other hand, its response to lithium prophylaxis seems to be lower, whereas it is the same when compared to classical BD in terms of response to valproate.
6. Conclusions Although the available data on UM do not warrant its classification as a separate nosological entity, the notion of UM has importance both in clinical and biological aspects. We need more such studies with standardized diagnostic criteria and crosscultural settings to clarify the issue. In this respect, the addition of UM as a longitudinal course specifier of BD in the diagnostic systems could be a crucial step.
Role of funding source The author of this paper has no funding source to report.
Conflict of interest The author of this paper has no conflicts of interest to report.
Acknowledgment I thank Ms. Kathyryn Kranzler and Mr. Hakan Gurvit, who kindly corrected the English expression of the paper.
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