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Journal of Affective Disorders
Volume 84, Issues 2-3 , February 2005, Pages 159-166
Bipolar Depression: Focus on Phenomenologydoi:10.1016/j.jad.2003.09.011
Copyright © 2005 Published by Elsevier B.V.
Research report
Profiles of "manic" symptoms in bipolar I, bipolar II and major depressive disorders
Alessandro Serretti , and Paolo OlgiatiDepartment of Psychiatry, Vita-Salute University, San Raffaele Institute, Via Stamira D'Ancona 20, 20127, Milan, Italy
Received 25 February 2003; accepted 9 September 2003. Available online 19 November 2003.
Abstract
Background: Classical authors such as Kraepelin, as well as the emerging literature during the past decade, indicate that manic-like signs and symptoms are present to a variable degree in all mood disorders. Current nosography does not differentiate between them and only the number of symptoms or severity is used for classification. This is particularly true for mania and hypomania. This paper will analyze the patterns of manic symptoms in bipolar I (BP-I), bipolar II (BP-II) and major depressive disorders (MDD), to test the hypothesis that mania and hypomania have different profiles, and ascertain which excitatory manic phenomena do occur in unipolar MDD. Methods: Six hundred and fifty-two inpatients (158 BP-I, 122 BP-II and 372 MDD) were assessed using the operational criteria for psychotic illness checklist (OPCRIT) [Arch. Gen. Psychiatry 48 (1991) 764] with a lifetime perspective. Manic or hypomanic symptoms were investigated and compared between BP-I, BP-II and MDD. Results: When compared with BP-II, BP-I disorder had a higher prevalence of reckless activity, distractibility, psychomotor agitation, irritable mood and increased self-esteem. These five symptoms correctly classified 82.8% of BP-I and 80.1% of BP-II patients. One or two manic symptoms were observed in more than 30% of major depressive patients; psychomotor agitation was the most frequent manifestations present in 18% of the MDD group. Limitations: We did not control for severity of symptoms, nor for neuroleptic use that could produce akathisia. Conclusions: This study suggests that mania and hypomania can be differentiated in their symptom profiles, and highlights the presence of few manic symptoms, particularly psychomotor agitation, in MDD. From the standpoint of number of manic signs and symptoms, controlling for psychomotor agitation did not substantially change the predictive power of the remaining manic symptoms. Given that excitatory manic signs and symptoms are present to a decreasing degree in BP-I, BP-II and MDD, these disorders can be proposed to lie along a dimensional model. Overall, these data are compatible with the concept of a bipolar spectrum, whereby each of the affective subtypes requires specific genetic factors.
Author Keywords: Bipolar disorder; Hypomania; Symptomatology; Affective disorders
1. Introduction
According to DSM IV (American Psychiatric Association, 1994), mania and hypomania, which respectively identify bipolar I (BP-I) and bipolar II (BP-II) disorder, have the same clinical profile (apart from psychotic symptoms, that can occur in mania alone) and differ only in the degree of severity. In fact, the diagnosis of mania requires a longer minimum duration (7 vs. 4 days), more functional impairment or hospitalization. Yet different lines of evidence, including family history, long-term diagnostic stability and linkage studies (Coryell et al., 1995; Coryell, 1999; Angst, 1998; Akiskal et al., 1977; Akiskal et al., 2000; Cassano et al., 1992; MacKinnon et al., 1998 and Benazzi, 1999), support the distinction between BP-I and BP-II disorder. This suggests that hypomania is not merely a less severe form of mania and different clinical phenomenology might characterize the two syndromes (Benazzi and Akiskal, 2003 and Hantouche et al., 2003a).
Manic and depressive symptoms co-exist in "Mixed States", originally described by Kraepelin (1909–1915). The recent literature focused on depressive mixed state (DMX), consisting of a major depressive episode (MDE) with few (at least three) manic symptoms (Akiskal, 1996 and Benazzi and Akiskal, 2001). Common features of this syndrome, not specifically identified in DSM IV, are agitation, irritability, racing thoughts and talkativeness (Akiskal and Mallya, 1987; Akiskal, 1992; Akiskal, 1996 and Perugi et al., 1997). An increasing body of evidence supports its inclusion under bipolar disorders (Benazzi, 2000; Benazzi, 2001a; Benazzi, 2001b and Benazzi and Akiskal, 2001). Koukopoulos and Koukopoulos (1999) have actually suggested that agitated depressions should be classified as mixed states. The foregoing results and considerations might depend on the use of high diagnostic thresholds. In fact, DMX2 (MDE plus no more than two manic symptoms) was much less specific for bipolar disorders, and much more frequent among unipolar depressives than DMX3, the form with a higher threshold of three manic symptoms (Benazzi, 2000; Benazzi, 2001a; Benazzi, 2001b and Benazzi and Akiskal, 2001).
This suggests that few (e.g. one or two) manic symptoms might be relatively common in unipolar depression, which would question the traditional bipolar–unipolar distinction. Most available data on DMX were achieved from cross-sectional studies performed on outpatients (Benazzi, 2000; Benazzi, 2001a and Benazzi, 2001b). This setting might have underestimated the prevalence of certain manic manifestations. In particular psychomotor agitation was found to occur more frequently among inpatients (Sobin and Sackeim, 1997 and Schatzberg and DeBattista, 1999). We are aware of only one previous paper specifically examining manic symptoms in bipolar and unipolar inpatients (Sato et al., 2003).
The current paper will compare manic symptoms occurring in BP-I and BP-II disorders to test the hypothesis that mania and hypomania differ in their clinical profiles. Furthermore, we will analyze the prevalence of few (one or two) manic symptoms in unipolar MDD inpatients.
2. Patients and method
2.1. Clinical sample
This study was conducted on subjects admitted to the Center for Mood Disorders of St. Raffaele Hospital in Milan, a specialized institution for treatment of mood disorders with 50 acute inpatients and about 3000 outpatients. Over 2000 new cases visited our center during the study period (1992–2000). Of those, we selected 652 inpatients, excluding individuals with mental retardation, dementia, substance abuse/dependence, neurological disorder or clinical/laboratory indications of severe organic disease. These subjects so-selected had participated in previous genetic studies (Serretti and Smeraldi, 1999; Serretti et al., 1998a; Serretti et al., 1998b; Serretti et al., 1999a; Serretti et al., 1999b and Serretti et al., 1999c), and were a part of a greater patient pool analyzed in clinical and demographic comparisons which did not involve manic symptomatology (Serretti et al., 2002).
Data were collected after obtaining informed consent for studies like the present one and the procedure was reviewed by the local ethical committee. The sample for the present analyses consisted of 223 males and 429 females, all of Caucasian origin: 158 patients were BP-I, 122 were BP-II and 372 had major depressive disorder (MDD). Of the MDD, 117 had one or two manic symptoms and were classified as "manic major depressives" (MMD).
2.2. Diagnostic procedures
Lifetime diagnoses were assigned by two independent psychiatrists on the basis of clinical interviews and medical records (Leckman et al., 1982), according to DSM-III-R and DSM-IV criteria (American Psychiatric Association, 1987; American Psychiatric Association, 1994 and Spitzer et al., 1990). All patients were assessed using the operational criteria for psychotic illness checklist (OPCRIT). This scale, described in detail elsewhere (McGuffin et al., 1991), was administered with a lifetime perspective to ascertain manic symptoms ever occurred during the course of illness (Farmer et al., 1994). Information was obtained not only from patients, interviewed during hospitalization, but also from their relatives and, whenever possible, from medical records. Out of a list of 90 OPCRIT items, we selected those 10 corresponding to symptoms included in DSM IV Criteria A and B for hypomanic/manic episode—elevated mood, irritable mood, increased self-esteem, reduced need for sleep, pressured speech, thoughts racing, distractibility, excessive activity, agitated activity, reckless activity, and other four items providing information on key variables reported to distinguish bipolar from unipolar disorders—gender, age at onset, mode of onset and familiarity.
2.3. Statistical analyses
Clinical and demographic variables were compared in BP-I, BP-II and major depressive patients (subdivided into MMD and pure MDD) by means of ANOVA and 2-test. Unipolar patients were subdivided into psychotic and non-psychotic groups. Fisher's exact test was used to test differences in the clinical pictures of manic (BP-I) and hypomanic (BP-II) episodes. Owing to the large number of comparisons, alpha was considered significant when <0.01. Finally a Wilkes-lambda discriminant analysis was performed on those manifestations which most differed between bipolar groups. The analysis was conducted with and without the inclusion of agitated activity (see Section 4).
3. Results
On demographic and general clinical characteristics (i.e. age and manner of onset), compared with MDD, BP-I disorder had a higher prevalence of males (X2=18.99, P<0.001), a lower age at onset (t=7.10, P<0.001), and a more rapid onset (X2=46.97, P<0.001) and a more frequent family history of mental diseases (X2=13.31 P<0.001).
Although there were more females in BP-II disorder the difference with BP-I this finding, however, was not statistically significant (X2=4.87 P=0.027). MMD was similar to pure major depression on all demographic comparators (not shown).
On manic symptomatology, when compared with BP-II, BP-I disorder had higher rates of reckless activity, distractibility, agitated activity, irritable mood and increased self-esteem (see Table 1). These five symptoms correctly classified 82.8% of BP-I and 80.8% of BP-II patients. After the exclusion of agitated activity, 80.2% of BP-I and 71.3% of bipolar II patients could still be assigned to correct diagnostic groups (see Table 2).
Agitated activity was the most frequent "manic symptom" in the major depressive group, followed by irritable mood, distractibility, reduced need for sleep and reckless activity. In psychotic depression, the rate of agitated activity was about three times higher than in non-psychotic major depression (see Table 3).
4. Discussion
The distinction between BP-I and BP-II disorders has been supported by biological variables, such as the distribution of *BO blood type (Rihmer and Arato, 1981), the red blood cell/plasma ratio of lithium (Rihmer et al., 1982) and serum dopamine-beta-hydroxylase activity (Rihmer et al., 1984), as well as clinical variables including characteristics of prior episode, family history and risk for suicide attempts (Dunner et al., 1976; Heun and Maier, 1993; Coryell, 1996; Cassano et al., 1992; Angst, 1998; Goldring and Fieve, 1984; Goodwin and Jamison, 1990 and Rihmer and Pestality, 1999). More recently, BP-IIs revealed a significantly higher lifetime prevalence of anxiety disorders, in particular social and simple phobias, and a substantially more chronic course, with more major and minor depressive episodes and shorter inter-episode intervals (Judd et al., 2003). Interestingly we found that also the patterns of manic symptoms could differentiate these two forms. Based on five manifestations—reckless activity, distractibility, psychomotor agitation, irritable mood and increased self-esteem—more than 80% of patients were correctly classified as manic (BP-I) or hypomanic (BP-II). In these analysis, one important confounding factor was antipsychotic treatment. In fact, psychomotor agitation can hardly be distinguished from akathisia, a well recognized side effect of conventional neuroleptics. The OPCRIT checklist does not assess drug therapy and detailed lifetime treatment information was not available for the sample. However even excluding psychomotor agitation still 80% of BP-I and 70% of BP-II patients could be correctly classified. Such results appear contrary to DSM IV (American Psychiatric Association, 1994), that describes manic episodes as nearly identical to hypomanic ones apart from a higher degree of severity and the possible occurrence of psychotic symptoms. In the literature, a number of factor analyses assessed the structure of mania (Cassidy et al., 1998; Serretti et al., 1999d; Swann et al., 2001; Hantouche et al., 2001; Akiskal et al., 2001; Rossi et al., 2001 and Sato et al., 2002) and hypomania (Benazzi and Akiskal, 2003 and Hantouche et al., 2003a). Overall, these studies displayed more dimensions (three to six) and a broader spectrum of symptoms in manic states. In particular, psychomotor agitation and poor judgment, often leading to involvement in reckless activities, were reported to be common in manic (Akiskal et al., 2003), but not in hypomanic patients (Benazzi and Akiskal, 2003). These findings are consistent with ours, and can serve to address the question of two disorders: it could be hypothesized that the different manic profiles are a manifestation of a greater severity, or that they reflect different physiopathology.
We also found one or two manic symptoms in more than 30% of patients with MDD, whose diagnostic assessment was integrated with the analysis of clinical and demographic variables which enabled to differentiate between bipolar and unipolar subjects. Psychomotor agitation, irritability and distractibility were the most prevalent manic-like manifestations in this unipolar subgroup. Interestingly this pattern of symptoms was similar to that observed in bipolar DMX (Benazzi and Akiskal, 2001), except for a higher prevalence of agitation. This might be due to the different characteristics of the samples. In fact Benazzi and Akiskal (2001) examined outpatients, whereas psychomotor agitation was shown to occur more frequently among inpatients (Sobin and Sackeim, 1997 and Schatzberg and DeBattista, 1999). Nonetheless, Sato et al. (2003) did replicate among inpatients the findings of Benazzi and Akiskal (2001).
Altogether our findings point to manic-like symptoms being present in all mood disorders, which contradicts the concept of the bipolar–unipolar distinction. A dispute exists between those who regard bipolar and unipolar disorders as different diseases (splitters), and those who include bipolar and unipolar forms in the same continuum (lumpers). Our results are more consistent with the latter position.
One possible remark is that our unipolar group might actually consist of "pseudo-unipolar" patients (Akiskal, 1983). Indeed 34.9% of MDD patients had psychotic manifestations and some authors have reported that psychotic delusional depression is more likely to occur in bipolar disorders (Akiskal et al., 1983 and Mitchell et al., 2001).
Nonetheless a relatively high prevalence of manic-like symptoms (26%) was found in non-psychotic MDD patients as well. Those may be the subjects with higher bipolar family history (Akiskal and Benazzi, 2003), unfortunately we had no data to test this possibility.
The presence of psychomotor agitation in a high proportion of unipolar depressions might have important consequences for clinical practice. In fact psychomotor agitation was listed among factors increasing the probability of suicide in depression (Fawcett, 1992 and Angst et al., 1999) and it was reported to be exacerbated by some antidepressant treatments (Akiskal and Pinto, 1999 and Koukopoulos and Koukopoulos, 1999).
In our sample, agitation was 3-fold commoner in psychotic than in non-psychotic depression. Such a difference might be in part the effect of drug therapy. But in our department antidepressant monotherapy is the routine, and the combination with antipsychotics is a second choice, thus, only in the psychotic group, a small proportion of agitated behaviors could be better understood as expressions of akathisia (Muscettola et al., 1999 and Berardi et al., 2000). Anyway even with the removal of such percentages attributable to drugs, psychotic depressives would maintain an almost twice higher prevalence rate of agitation (20.7% vs. 11.9% observe in non-psychotic MDD). This supports the association between psychotic depression and psychomotor agitation independently of neuroleptic use. Besides incomplete information about drug treatment, another limitation of our study is that symptoms were not rated on their severity. This is a problem because hypomania is regarded as a milder form of mania, thus the same manifestations might be less severe. Moreover we did not include other symptoms such as anxiety or obsessive symptoms, both of which have a bearing on bipolarity and its subtyping (Perugi et al., 1999 and Hantouche et al., 2003b). Indeed, there is linkage analysis data to support some uniqueness to the BP-I and BP-II subtype (MacKinnon et al., 1998 and Collier et al., 1996).
A strength of our study is that a lifetime perspective was applied to assess current and past symptoms gathered from various sources: patients themselves, interviewed during hospitalization, members of patients’ families and, when available, medical charts. In addition the use of complementary sources of information (relatives, medical records) reduced biases related to self-report of symptoms.
In conclusion, this study unveiled specific clinical profiles in mania and hypomania and the occurrence of few manic symptoms, particularly psychomotor agitation, in a relatively high proportion of unipolar inpatients. The latter finding might be interpreted in support of the hypothesis of bipolar-unipolar clinical continuity or spectrum (Akiskal, 1983 and Akiskal, 2002), with some common susceptibility genes modifying the presentation of the two forms (Gershon et al., 1982; Serretti et al., 1996 and Kelsoe, 2003).
Acknowledgements
The authors thank Cristina Cusin for her help in writing the manuscript.
References
Akiskal, H.S., 1983. The bipolar spectrum: new concepts in classification and diagnosis. In: Grinspoon, L., Editor, 1983. Psychiatry Update: The American Psychiatric Association Annual Review vol. 2, American Psychiatric Press, Washington, DC, pp. 271–292.
Akiskal, H.S., 1992. The distinctive mixed states of bipolar I, II, and III. Clin. Neuropharm. 15 Suppl. 1, pp. 632A–633A. Abstract-MEDLINE
Akiskal, H.S., 1996. The prevalent clinical spectrum of bipolar disorders: beyond DSM-IV. J. Clin. Psychopharmacol. 16 Suppl. 1, pp. 4S–14S. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Akiskal, H.S., 2002. The bipolar spectrum—the shaping of a new paradigm. Curr. Psychiatry Rep. 4, pp. 1–3. Abstract-MEDLINE
Akiskal, H.S. and Benazzi, F., 2003. Family history validation of the bipolar nature of depressive mixed states. J. Affect. Disord. 73, pp. 113–122. SummaryPlus | Full Text + Links | PDF (86 K)
Akiskal, H.S. and Mallya, G., 1987. Criteria for the ‘soft’ bipolar spectrum: treatment implications. Psychopharmacol. Bull. 23, pp. 68–73. Abstract-EMBASE | Abstract-MEDLINE
Akiskal, H.S. and Pinto, O., 1999. The evolving bipolar spectrum: prototypes I, II, III, and IV. Psychiatr. Clin. North Am. 22, pp. 517–534. Abstract-EMBASE | Abstract-PsycINFO
Akiskal, H.S., Djenderedjian, A.H., Rosenthal, R.H. and Khani, M.K., 1977. Cyclothymic disorder: validating criteria for inclusion in the bipolar affective group. Am. J. Psychiatry 134, pp. 1227–1233. Abstract-EMBASE | Abstract-PsycINFO
Akiskal, H.S., Walker, P.W., Puzantian, V.R., King, D., Rosenthal, T.L. and Dranon, M., 1983. Bipolar outcome in the course of depressive illness: phenomenologic, familial, and pharmacologic predictors. J. Affect. Disord. 5, pp. 115–128. Abstract
Akiskal, H.S., Bourgeois, M.L., Angst, J., Post, R., Moller, H. and Hirschfeld, R., 2000. Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. J. Affect. Disord. 59 Suppl. 1, pp. S5–S30. Abstract | PDF (1304 K)
Akiskal, H.S., Hantouche, E.G., Bourgeois, M.L., Azorin, J.M., Sechter, D., Allilaire, J.F., Chatenet-Duchene, L. and Lancrenon, S., 2001. Toward a refined phenomenology of mania: combining clinician-assessment and self-report in the French EPIMAN study. J. Affect. Disord. 67, pp. 89–96. SummaryPlus | Full Text + Links | PDF (69 K)
Aiskal, H.S., Azorin, J.M. and Hantouche, E.G., 2003. Proposed multidimensional structure of mania: beyond the euphoric dysphoric dichotomy. J. Affect. Disord. 73, pp. 7–18.
American Psychiatric Association, 1987. Diagnostic and Statistical Manual of Mental Disorders. (3rd ed.), American Psychiatric Association, Washington, DC Revised .
American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders. (4th ed.), American Psychiatric Association, Washington, DC.
Angst, J., 1998. The emerging epidemiology of hypomania and bipolar II disorder. J. Affect. Disord. 50, pp. 143–151. SummaryPlus | Full Text + Links | PDF (112 K)
Angst, J., Angst, F. and Stassen, H.H., 1999. Suicide risk in patients with major depressive disorder. J. Clin. Psychiatry 60 Suppl. 2, pp. 57–62. Abstract-EMBASE | Abstract-PsycINFO
Benazzi, F., 1999. A comparison of the age of onset of bipolar I and bipolar II outpatients. J. Affect. Disord. 54, pp. 249–253. SummaryPlus | Full Text + Links | PDF (53 K)
Benazzi, F., 2000. Depressive mixed states: unipolar and bipolar II. Eur. Arch. Psychiatry Clin. Neurosci. 250, pp. 249–253. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO | Full Text via CrossRef
Benazzi, F., 2001. Depressive mixed state: testing different definitions. Psychiatry Clin. Neurosci. 55, pp. 647–652. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO | Full Text via CrossRef
Benazzi, F., 2001. Sensitivity and specificity of clinical markers for the diagnosis of bipolar II disorder. Compr. Psychiatry 42, pp. 461–465. Abstract | PDF (41 K)
Benazzi, F. and Akiskal, H.S., 2001. Delineating bipolar II mixed states in the Ravenna–San Diego collaborative study: the relative prevalence and diagnostic significance of hypomanic features during major depressive episodes. J. Affect. Disord. 67, pp. 115–122. SummaryPlus | Full Text + Links | PDF (70 K)
Benazzi, F. and Akiskal, H.S., 2003. The dual factor structure of self-rated MDQ hypomania: energized-activity versus irritable-thought racing. J. Affect. Disord. 73, pp. 59–64. SummaryPlus | Full Text + Links | PDF (67 K)
Berardi, D., Giannelli, A. and Barnes, T.R., 2000. Clinical correlates of akathisia in acute psychiatric inpatients. Int. Clin. Psychopharmacol. 15, pp. 215–219. Abstract-EMBASE | Abstract-Elsevier BIOBASE | Abstract-MEDLINE | Abstract-PsycINFO
Cassano, G.B., Akiskal, H.S., Savino, M., Musetti, L. and Perugi, G., 1992. Proposed subtypes of bipolar II and related disorders: with hypomanic episodes (or cyclothymia) and with hyperthymic temperament. J. Affect. Disord. 26, pp. 127–140. Abstract
Cassidy, F., Forest, K., Murry, E. and Carroll, B.J., 1998. A factor analysis of the signs and symptoms of mania. Arch. Gen. Psychiatry 55, pp. 27–32. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO | Full Text via CrossRef
Collier, D., Stöber, G., Li, T., Heils, A., Catalano, M., Di Bella, D., Arranz, M., Murray, R., Vallada, H., Bengel, D., Müller-Reible, C., Roberts, G., Smeraldi, E., Kirov, G., Sham, P. and Lesh, P., 1996. A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol. Psychiatry 1, pp. 453–460. Abstract-MEDLINE
Coryell, W., 1996. Bipolar II disorder: a progress report. J. Affect. Disord. 41, pp. 159–162. Abstract | Abstract + References | PDF (405 K)
Coryell, W., 1999. Bipolar II disorder: the importance of hypomania. In: Goldberg, J.F. and Harrow, M., Editors, 1999. Bipolar Disorders. Clinical Course and Outcome, American Psychiatric Press, Washington, DC, pp. 219–236.
Coryell, W., Endicott, J., Maser, J.D., Keller, M.B., Leon, A.C. and Akiskal, H.S., 1995. Long-term stability of polarity distinctions in the affective disorders. Am. J. Psychiatry 152, pp. 385–390. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Dunner, D.L., Gershon, E.S. and Goodwin, F.K., 1976. Heritable factors in the severity of affective illness. Biol. Psychiatry 11, pp. 31–42. Abstract-EMBASE | Abstract-MEDLINE
Farmer, A.E., Williams, J. and Jones, I., 1994. Phenotypic definitions of psychotic illness for molecular genetic research. Am. J. Med. Genet. 54, pp. 365–371. Abstract-EMBASE | Abstract-MEDLINE
Fawcett, J., 1992. Suicide risk factors in depressive disorders and in panic disorder. J. Clin. Psychiatry 53 Suppl. 3, pp. 9–13. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Gershon, E.S., Hamovit, J., Guroff, J.J., Dibble, E., Leckman, J.F., Sceery, W., Targum, S.D., Nurnberger Jr., J.I., Goldin, L.R. and Bunney Jr., W.E., 1982. A family study of schizoaffective, bipolar I, bipolar II, unipolar and control probands. Arch. Gen. Psychiatry 39, pp. 1157–1167. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Goldring, N. and Fieve, R.R., 1984. Attempted suicide in manic-depressive disorder. Am. J. Psychother. 38, pp. 373–383. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Goodwin, F. and Jamison, K., 1990. Manic-depressive Illness. , Oxford University Press, New York.
Hantouche, E.G., Allilaire, J.P., Bourgeois, M.L., Azorin, J.M., Sechter, D., Chatenet-Duchene, L., Lancrenon, S. and Akiskal, H.S., 2001. The feasibility of self-assessment of dysphoric mania in the French national EPIMAN study. J. Affect. Disord. 67, pp. 97–103. SummaryPlus | Full Text + Links | PDF (61 K)
Hantouche, E.G., Angst, J. and Akiskal, H.S., 2003. Factor structure of hypomania: interrelationships with cyclothymia and the soft bipolar spectrum. J. Affect. Disord. 73, pp. 39–47.
Hantouche, E.G., Angst, J., Demonfaucon, C., Perugi, G., Lancrenon, S. and Akiskal, H.S., 2003. Cyclothymic OCD: a distinct form. J. Affect. Disord. 75, pp. 1–10. SummaryPlus | Full Text + Links | PDF (83 K)
Heun, R. and Maier, W., 1993. The distinction of bipolar II disorder from bipolar I and recurrent unipolar depression: results of a controlled family study. Acta Psychiatr. Scand. 87, pp. 279–284. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Judd, L.L., Akiskal, H.S., Schettler, P.J., Coryell, W., Maser, J., Rice, J.A., Solomon, D.A. and Keller, M.B., 2003. The comparative clinical phenotype and long-term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders. J. Affect. Disord. 73 1–2, pp. 19–32. SummaryPlus | Full Text + Links | PDF (109 K)
Kelsoe, J.R., 2003. Arguments for the genetic basis of the bipolar spectrum. J. Affect. Disord. 73, pp. 183–197. SummaryPlus | Full Text + Links | PDF (383 K)
Koukopoulos, A. and Koukopoulos, A., 1999. Agitated depression as a mixed state and the problem of melancholia. Psychiatr. Clin. North Am. 22, pp. 547–564. Abstract-EMBASE | Abstract-MEDLINE
Kraepelin, E., 1915. Psychiatrie. (8th ed.), Johann Ambrosius Barth, Leipzig.
Leckman, J.F., Sholomskas, D., Thompson, W.D., Belanger, A. and Weissman, M.M., 1982. Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch. Gen. Psychiatry 39, pp. 879–883. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
MacKinnon, D.F., Xu, J., McMahon, F.J., Simpson, S.G., Stine, O.C., McInnis, M.G. and DePaulo, J.R., 1998. Bipolar disorder and panic disorder in families: an analysis of chromosome 18 data. Am. J. Psychiatry 155, pp. 829–831. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
McGuffin, P., Farmer, A. and Harvey, I., 1991. A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch. Gen. Psychiatry 48, pp. 764–770. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Mitchell, P.B., Wilhelm, K., Parker, G., Austin, M.P., Rutgers, P.P.P. and Malhi, G.S., 2001. The clinical features of bipolar depression: a comparison with matched major depressive patients. J. Clin. Psychiatry 62 3, pp. 212–216. Abstract-EMBASE | Abstract-PsycINFO
Muscettola, G., Barbato, G., Pampallona, S., Casiello, M. and Bollini, P., 1999. Extrapyramidal syndromes in neuroleptic-treated patients: prevalence, risk factors, and association with tardive dyskinesia. J. Clin. Psychopharmacol. 19, pp. 203–220.
Perugi, G., Akiskal, H.S., Micheli, C., Musetti, L., Paiano, A., Quilici, C., Rossi, L. and Cassano, G.B., 1997. Clinical subtypes of bipolar mixed states: validating a broader european definition in 143 cases. J. Affect. Disord. 43, pp. 169–180. Abstract | PDF (813 K)
Perugi, G., Toni, C. and Akiskal, H.S., 1999. Anxious-bipolar comorbidity. Diagnostic and treatment challenges. Psychiatr. Clin. North Am. 22, pp. 565–583. Abstract-EMBASE
Rihmer, Z. and Arato, M., 1981. *BO blood groups in manic-depressive patients. J. Affect. Disord. 3 1, pp. 1–7. Abstract
Rihmer, Z. and Pestality, P., 1999. Bipolar II disorder and suicidal behavior. Psychiatr. Clin. North Am. 22, pp. 667–673 (ix–x) . Abstract-EMBASE | Abstract-PsycINFO
Rihmer, Z., Arato, M., Szentistvanyi, I. and Banki, C.M., 1982. The red blood cell/plasma lithium ratio: marker of biological heterogeneity within bipolar affective illness. Psychiatry Res. 6 2, pp. 197–201. Abstract
Rihmer, Z., Bagdy, G. and Arato, M., 1984. Serun dopamine-beta-hydroxylase activity in female manic-depressive patients. Biol. Psychiatry 19 3, pp. 423–427. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Rossi, A., Daneluzzo, E., Arduini, L., Di Domenico, M., Pollice, R. and Petruzzi, C., 2001. A factor analysis of signs and symptoms of the manic episode with Bech–Rafaelsen Mania and Melancholia Scales. J. Affect. Disord. 64, pp. 267–270. SummaryPlus | Full Text + Links | PDF (47 K)
Sato, T., Bottlender, R., Kleindienst, N. and Moller, H.J., 2002. Syndromes and phenomenological subtypes underlying acute mania: a factor analytic study of 576 manic patients. Am. J. Psychiatry 159, pp. 968–974. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO | Full Text via CrossRef
Sato, T., Bottlender, R., Schroter, A. and Moller, H.J., 2003. Frequency of manic symptoms during a depressive episode and unipolar ‘depressive mixed state’ as bipolar spectrum. Acta. Psychiatr. Scand. 107, pp. 268–274. Abstract-EMBASE | Abstract-Elsevier BIOBASE | Abstract-MEDLINE | Abstract-PsycINFO | Full Text via CrossRef
Schatzberg, A.F. and DeBattista, C., 1999. Phenomenology and treatment of agitation. J. Clin. Psychiatry 60 15, pp. 17–20. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Serretti, A. and Smeraldi, E., 1999. Dopamine D2 receptor gene not associated with symptomatology of mood disorders. Am. J. Med. Genet. 88, pp. 294–297. Abstract-EMBASE | Abstract-MEDLINE
Serretti, A., Macciardi, F. and Smeraldi, E., 1996. Identification of symptomatologic patterns common to major psychoses: proposal for a phenotype definition. Am. J. Med. Genet. 67, pp. 393–400. Abstract-MEDLINE | Full Text via CrossRef
Serretti, A., Franchini, L., Gasperini, M., Rampoldi, R. and Smeraldi, E., 1998. Mode of inheritance in mood disorders families according to fluvoxamine response. Acta Psychiatr. Scand. 98, pp. 443–450. Abstract-EMBASE | Abstract-MEDLINE
Serretti, A., Macciardi, F., Cusin, C., Lattuada, E., Lilli, R. and Smeraldi, E., 1998. Dopamine receptor D4 gene is associated with delusional symptomatology in mood disorders. Psychiatry Res. 80, pp. 129–136. SummaryPlus | Full Text + Links | PDF (90 K)
Serretti, A., Cusin, C., Lattuada, E., Di Bella, D., Catalano, M. and Smeraldi, E., 1999. Serotonin transporter gene (5-HTTLPR) is not associated with depressive symptomatology in mood disorders. Mol. Psychiatry 4, pp. 280–283. Abstract-EMBASE
Serretti, A., Lilli, R., Lorenzi, C., Gasperini, M. and Smeraldi, E., 1999. Tryptophan hydroxylase gene and response to lithium prophylaxis in mood disorders. J. Psychiatric Res. 33, pp. 371–377. SummaryPlus | Full Text + Links | PDF (135 K)
Serretti, A., Macciardi, F., Catalano, M., Bellodi, L. and Smeraldi, E., 1999. Genetic variants of dopamine receptor D4 and psychopathology. Schizophr. Bull. 25, pp. 609–618. Abstract-EMBASE | Abstract-Elsevier BIOBASE | Abstract-MEDLINE | Abstract-PsycINFO
Serretti, A., Rietschel, M., Lattuada, E., Krauss, H., Held, T., Nothen, M. and Smeraldi, E., 1999. Factor analysis of mania. Arch. Gen. Psychiatry 56, pp. 671–672. Abstract-MEDLINE | Abstract-PsycINFO | Full Text via CrossRef
Serretti, A., Mandelli, L., Lattuada, E., Cusin, C. and Smeraldi, E., 2002. Clinical and demographic features of mood disorder subtypes. Psychiatry Res. 112, pp. 195–210. SummaryPlus | Full Text + Links | PDF (181 K)
Sobin, C. and Sackeim, H.A., 1997. Psychomotor symptoms of depression. Am. J. Psychiatry 154, pp. 4–17. Abstract-EMBASE | Abstract-MEDLINE | Abstract-PsycINFO
Spitzer, R.L., Williams, J.B.W., Gibbon, M. and First, M.B., 1990. Structured Clinical Interview for DSM-III-R, Version 1.0 (SCID). , American Psychiatric Press, Washington, DC.
Swann, A.C., Janicak, P.L., Calabrese, J.R., Bowden, C.L., Dilsaver, S.C., Morris, D.D., Petty, F. and Davis, J.M., 2001. Structure of mania: depressive, irritable, and psychotic clusters with different retrospectively-assessed course patterns of illness in randomized clinical trial participants. J. Affect. Disord. 67, pp. 123–132. SummaryPlus | Full Text + Links | PDF (159 K)
Corresponding author. Tel.: +39-02-2643-3250; fax: +39-02-2643-3265.
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