Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-25T19:58:32.509Z Has data issue: false hasContentIssue false
  • English
  • Français

Mixed features: evolution of the concept, past and current definitions, and future prospects

Published online by Cambridge University Press:  07 March 2017

Alan C. Swann
Alan C. Swann*
Affiliation:
Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
*
*Address correspondence to: Alan C. Swann, Baylor College of Medicine, Department of Psychiatry, 1977 Butler Boulevard, Suite E4.400, Houston, Texas 7030, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Mixed states address the relationships between episodes and the course of an illness, presenting significant clinical challenges. Recurrent affective disorders were described thousands of years ago as dimensional disturbances of the basic elements of behavior, combining the characteristics of what we would now consider manic and depressive episodes. It was recognized from the beginning that combinations of depressive and manic features are associated with a severe illness course, including increased suicide risk. Early descriptions of affective disorders formulated them as systemic illnesses, a concept supported by more recent data. Descriptions of affective disorders and their course, including mixed states, became more systematic during the 19th century. Structured criteria achieved importance with evidence that, in addition to early onset, frequent recurrence, and comorbid problems, mixed states had worse treatment outcomes than other episodes. In contrast to 2000 years of literature on recurrent affective episodes and mixed states, the unipolar–bipolar disorder distinction was formalized in the mid-20th century. Mixed-state criteria, initially developed for bipolar disorder, ranged from fully combined depression and mania to the DSM–5 criteria, no longer limited to bipolar disorder, of a primary depressive or manic episode with at least three symptoms of the other episode type. The challenges involved in understanding and identifying mixed states center largely on what drives them, including (1) their formulation as either categorical or dimensional constructs, (2) the specificity of their relationships to depressive or manic episodes, and (3) specificity for bipolar versus major depressive disorder. Their existence challenges the distinction between bipolar and major depressive disorders. The challenges involved in identifying the underlying physiological mechanisms go to the heart of these questions.

Keywords

Mixed stateshistoryaffective disordersmodelstheoreticaldepressionmaniadiagnosisreview
Type
Review Articles
Information
CNS Spectrums , Volume 22 , Issue 2: Theme: Mixed features in major depressive episodes , April 2017 , pp. 161 - 169
Copyright
© Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Support was provided by the Mental Health Care Line at the Michael E. DeBakey Veterans Affairs Medical Center.

References

1. Aretaeus. On the Causes and Symptoms of Chronic Disease. Boston: Milford House; 1972.Google Scholar
2. Gelder, M, Gath, D, Mayou, R, Cowen, P. Oxford Textbook of Psychiatry, 3rd ed. Oxford: Oxford University Press; 1998.Google Scholar
3. Mathews, M. How Did Pre-Twentieth Century Theories of the Aetiology of Depression Develop? Brighton: Priory Lodge Education; 2004.Google Scholar
4. Alexander, FG, Selesnick, ST. The History of Psychiatry: An Evaluation of Psychiatric Thought and Practice from Prehistoric Times to the Present. New York: Harper & Row; 1966.Google Scholar
5. Hippocrates. The Genuine Works of Hippocrates. New York: Dover; 1868.Google Scholar
6. Ackerknecht, EH. A Short History of Psychiatry [in German]. Trans S Wolff New York: Hafner; 1959.Google Scholar
7. Johnstone, EC, Freeman, CPL, Zealey, AK. eds. Companion to Psychiatric Studies, 6th ed. Edinburgh: Churchill Livingstone; 1998.Google Scholar
8. Angst, J, Marneros, A. Bipolarity from ancient to modern times: conception, birth and rebirth. J Affect Disord. 2001; 67(1–3): 3–19.Google Scholar
9. Kraepelin, E. Manic-Depressive Illness and Paranoia. Edinburgh: Livingstone; 1921.Google Scholar
10. Weygandt, W. Uber die Mischzustande des Manisch-Depressiven Irreseins [in German]. Munich: Verlag von J.F. Lehmann; 1899.Google Scholar
11. Galen. On the Natural Faculties. Cambridge: Harvard University Press; 1916.Google Scholar
12. Berk, M, Kapczinski, F, Andreazza, AC, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 2011; 35(3): 804–817.Google Scholar
13. Luo, Y, He, H, Zhang, M, Huang, X, Fan, N. Altered serum levels of TNF-α, IL-6 and IL-18 in manic, depressive, mixed state of bipolar disorder patients. Psychiatry Res. 2016; 244: 19–23. Epub ahead of print Jul 18.CrossRefGoogle ScholarPubMed
14. Aretaeus. On the Causes and Symptoms of Acute Disease. Boston: Milford House; 1972.Google Scholar
15. Iasevoli, F, Valchera, A, Di Giovambattista, E, et al. Affective temperaments are associated with specific clusters of symptoms and psychopathology: a cross-sectional study on bipolar disorder inpatients in acute manic, mixed, or depressive relapse. J Affect Disord. 2013; 151(2): 540–550. Epub ahead of print Jul 12.Google Scholar
16. Mazzarini, L, Pacchiarotti, I, Colom, F, et al. Predominant polarity and temperament in bipolar and unipolar affective disorders. J Affect Disord. 2009; 119(1–3): 28–33. Epub ahead of print Apr 5.CrossRefGoogle ScholarPubMed
17. Perugi, G, Micheli, C, Akiskal, HS, et al. Polarity of the first episode, clinical characteristics, and course of manic depressive illness: a systematic retrospective investigation of 320 bipolar I patients. Compr Psychiatry. 2000; 41(1): 13–18.Google Scholar
18. Schneider, K. Klinische Psychopathologie [in German], 5th ed. Stuttgart: Thieme; 1959.Google Scholar
19. Secunda, SK, Katz, MM, Swann, A, et al. Mania: diagnosis, state measurement and prediction of treatment response. J Affect Disord. 1985; 8(2): 113–121.Google Scholar
20. Himmelhoch, JM, Mulla, D, Neil, JF, Detre, TP, Kupfer, DJ. Incidence and severity of mixed affective states in a bipolar population. Arch Gen Psychiatry. 1976; 33(9): 1062–1066.Google Scholar
21. Himmelhoch, JM, Garfinkel, ME. Sources of lithium resistance in mixed mania. Psychopharmacol Bull. 1986; 22(3): 613–620.Google Scholar
22. Leonhard, K. On monopolar and bipolar endogenous psychoses [in German]. Nervenarzt. 1968; 39(3): 104–106.Google Scholar
23. Benazzi, F, Akiskal, HS. How best to identify a bipolar-related subtype among major depressive patients without spontaneous hypomania: superiority of age at onset criterion over recurrence and polarity? J Affect Disord. 2008; 107(1–3): 77–88. Epub ahead of print Sep 12, 2007.Google Scholar
24. Akiskal, HS, Maser, JD, Zeller, PJ, et al. Switching from “unipolar” to bipolar II: an 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry. 1994; 52(2): 114–123.Google Scholar
25. Winokur, G, Wesner, R. From unipolar depression to bipolar illness: 29 who changed. Acta Psychiatr Scand. 1987; 76(1): 59–63.CrossRefGoogle ScholarPubMed
26. Benazzi, F. Classifying mood disorders by age-at-onset instead of polarity. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(1): 86–93.CrossRefGoogle ScholarPubMed
27. Bowden, CL, Lecrubier, Y, Bauer, M, et al. Maintenance therapies for classic and other forms of bipolar disorder. J Affect Disord. 2000; 59(Suppl 1): S57–S67.Google Scholar
28. Akiskal, HS, Benazzi, F. Family history validation of the bipolar nature of depressive mixed states. J Affect Disord. 2003; 73(1–2): 113–122.CrossRefGoogle ScholarPubMed
29. Zimmermann, P, Bruckl, T, Nocon, A, et al. Heterogeneity of DSM–IV major depressive disorder as a consequence of subthreshold bipolarity. Arch Gen Psychiatry. 2009; 66(12): 1341–1352. http://jamanetwork.com/journals/jamapsychiatry/fullarticle/210481.Google Scholar
30. Benazzi, F, Akiskal, HS. 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. 2001; 67(1–3): 115–122.Google Scholar
31. Azorin, JM, Aubrun, E, Bertsch, J, Reed, C, Gerard, S, Lukasiewicz, M. Mixed states vs. pure mania in the French sample of the EMBLEM study: results at baseline and 24 months. European mania in bipolar longitudinal evaluation of medication. BMC Psychiatry. 2009; 9: 33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701946/pdf/1471-244X-9-33.pdf.Google Scholar
32. Benazzi, F. Challenging the unipolar–bipolar division: does mixed depression bridge the gap? Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31(1): 97–103. Epub ahead of print Sep 15.Google Scholar
33. Agosti, V, Stewart, JW. Hypomania with and without dysphoria: comparison of comorbidity and clinical characteristics of respondents from a national community sample. J Affect Disord. 2008; 108(1–2): 177–182. Epub ahead of print Oct 25, 2007.Google Scholar
34. Akiskal, HS, Benazzi, F, Perugi, G, Rihmer, Z. Agitated “unipolar” depression re-conceptualized as a depressive mixed state: implications for the antidepressant–suicide controversy. J Affect Disord. 2005; 85(3): 245–258.Google Scholar
35. Benazzi, F. The continuum/spectrum concept of mood disorders: is mixed depression the basic link? Eur Arch Psychiatry Clin Neurosci. 2006; 256(8): 512–515.Google Scholar
36. Biondi, M, Picardi, A, Pasquini, M, Gaetano, P, Pancheri, P. Dimensional psychopathology of depression: detection of an “activation” dimension in unipolar depressed outpatients. J Affect Disord. 2005; 84(2–3): 133–139.CrossRefGoogle ScholarPubMed
37. Fiedorowicz, JG, Endicott, J, Solomon, DA, Keller, MB, Coryell, WH. Course of illness following prospectively observed mania or hypomania in individuals presenting with unipolar depression. Bipolar Disord. 2012; 14(6): 664–671. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432672/pdf/nihms386648.pdf.Google Scholar
38. Swann, AC, Moeller, FG, Steinberg, JL, Schneider, L, Barratt, ES, Dougherty, DM. Manic symptoms and impulsivity during bipolar depressive episodes. Bipolar Disord. 2007; 9(3): 206–212. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723749/pdf/nihms128564.pdf.CrossRefGoogle ScholarPubMed
39. Benazzi, F. Mixed states in bipolar II disorder: should full hypomania always be required? Psychiatry Res. 2004; 127(3): 247–257.CrossRefGoogle ScholarPubMed
40. Swann, AC, Bowden, CL, Morris, D, et al. Depression during mania: treatment response to lithium or divalproex. Arch Gen Psychiatry. 1997; 54(1): 37–42.CrossRefGoogle ScholarPubMed
41. Swann, AC, Steinberg, JL, Lijffijt, M, Moeller, FG. Continuum of depressive and manic mixed states in patients with bipolar disorder: quantitative measurement and clinical features. World Psychiatry. 2009; 8(3): 166–172. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758583/pdf/wpa030166.pdf.Google Scholar
42. Pacchiarotti, I, Nivoli, AM, Mazzarini, L, et al. The symptom structure of bipolar acute episodes: in search for the mixing link. J Affect Disord. 2013; 149(1–3): 56–66. Epub ahead of print Feb 7.CrossRefGoogle ScholarPubMed
43. Baldessarini, RJ, Salvatore, P, Khalsa, HM, Tohen, M. Dissimilar morbidity following initial mania versus mixed-states in type-I bipolar disorder. J Affect Disord. 2010; 126(1–2): 299–302. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925064/pdf/nihms202298.pdf.Google Scholar
44. Sato, T, Bottlender, R, Sievers, M, Schröter, A, Kleindienst, N, Möller, HJ. Evaluating the inter-episode stability of depressive mixed states. J Affect Disord. 2004; 81(2): 103–113.Google Scholar
45. Swann, AC, Stokes, PE, Casper, R, Chang, S, Katz, MM, Garver, D. Hypothalamic–pituitary–adrenocortical function in mixed and pure mania. Acta Psychiatr Scand. 1992; 85(4): 270–274.Google Scholar
46. Swann, AC, Stokes, PE, Secunda, S, et al. Depressive mania versus agitated depression: biogenic amine and hypothalamic–pituitary–adrenocortical function. Biol Psychiatry. 1994; 35(10): 803–813.Google Scholar
47. Henry, C, M’Bailara, K, Desage, A, Gard, S, Misdrahi, D, Vieta, E. Towards a reconceptualization of mixed states, based on an emotional-reactivity dimensional model. J Affect Disord. 2007; 101(1–3): 35–41.CrossRefGoogle Scholar
48. Koukopoulos, A, Sani, G, Ghaemi, SN. Mixed features of depression: why DSM–5 is wrong (and so was DSM–IV). Br J Psychiatry. 2013; 203(1): 3–5. http://bjp.rcpsych.org/content/203/1/3.long.Google Scholar
49. Janzarik, W. Dynamische Grundkonstellationen in Endogenen Psychosen [Dynamic Basic Constellations in Endogenous Psychoses] [in German]. Berlin–Göttingen–Heidelberg: Springer; 1959.CrossRefGoogle Scholar
50. Berner, P, Gabriel, E, Katschnig, H, et al. Diagnostic Criteria for Schizophrenia and Affective Psychoses. Washington, DC: World Psychiatric Association/American Psychiatric Association; 1983.Google Scholar
51. Swann, AC, Secunda, SK, Katz, MM, et al. Lithium treatment of mania: clinical characteristics, specificity of symptom change, and outcome. Psychiatry Res. 1986; 18(2): 127–141.CrossRefGoogle ScholarPubMed
52. McElroy, SL, Keck, PE Jr, Pope, HG Jr, Hudson, JI, Faedda, GL, Swann, AC. Clinical and research implications of the diagnosis of dysphoric or mixed mania or hypomania. Am J Psychiatry. 1992; 149: 1633–1644.Google Scholar
53. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1995.Google Scholar
54. Cassidy, F, Murry, E, Forest, K, Carroll, BJ. The performance of DSM–III–R major depression criteria in the diagnosis of bipolar mixed states. J Affect Disord. 1997; 46(1): 79–81.Google Scholar
55. Suppes, T, Mintz, J, McElroy, SL, et al. Mixed hypomania in 908 patients with bipolar disorder evaluated prospectively in the Stanley Foundation Bipolar Treatment Network: a sex-specific phenomenon. Arch Gen Psychiatry. 2005; 62(10): 1089–1096. http://jamanetwork.com/journals/jamapsychiatry/fullarticle/208953.Google Scholar
56. Goodwin, FK, Jamison, KR. Manic-Depressive Illness. New York: Oxford University Press; 1990.Google Scholar
57. American Psychiatric Association. Diagnostic and Statistical Manual, 5th ed. Washington, DC: American Psychiatric Association; 2013.Google Scholar
58. Katz, MM, Wetzler, S, Cloitre, M, et al. Expressive characteristics of anxiety in depressed men and women. J Affect Disord. 1993; 28(4): 267–277.Google Scholar
59. Swann, AC, Secunda, SK, Katz, MM, et al. Specificity of mixed affective states: clinical comparison of mixed mania and agitated depression. J Affect Disord. 1993; 28(2): 81–89.Google Scholar
60. Koukopoulos, A, Sani, G. DSM–5 criteria for depression with mixed features: a farewell to mixed depression. Acta Psychiatr Scand. 2014; 129(1): 4–16. Epub ahead of print Apr 19, 2013.Google Scholar
61. Perugi, G, Angst, J, Azorin, JM, et al. Mixed features in patients with a major depressive episode: the BRIDGE–II–MIX study. J Clin Psychiatry. 2015; 76(3): e351–e358.Google Scholar
62. Verdolini, N, Agius, M, Ferranti, L, Moretti, P, Piselli, M, Quartesan, R. The state of the art of the DSM–5 “with mixed features” specifier. Scientific World Journal. 2015; 2015: 757258. Epub ahead of print Aug 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562096/pdf/TSWJ2015-757258.pdf.Google Scholar
63. Goldberg, D. Plato versus Aristotle: categorical and dimensional models for common mental disorders. Compr Psychiatry. 2000; 41(2 Suppl 1): 8–13.Google Scholar
64. Quitkin, FM, Rabkin, JG, Prien, RF. Bipolar disorder: are there manic-prone and depressive-prone forms? J Clin Psychopharmacol. 1986; 6(3): 167–172.Google Scholar
65. Swann, AC, Lafer, B, Perugi, G, et al. Bipolar mixed states: an international society for bipolar disorders task force report of symptom structure, course of illness, and diagnosis. Am J Psychiatry. 2013; 170(1): 31–42. http://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.2012.12030301.Google Scholar
66. Perugi, G, Medda, P, Swann, AC, Reis, J, Rizzato, S, Mauri, M. Phenomenological subtypes of severe bipolar mixed states: a factor analytic study. Compr Psychiatry. 2014; 55(4): 799–806. Epub ahead of print Jan 29.Google Scholar
67. Ghaemi, SN. Why antidepressants are not antidepressants: STEP–BD, STAR*D, and the return of neurotic depression. Bipolar Disord. 2008; 10(8): 957–968.Google Scholar
68. Ghaemi, SN, Rosenquist, KJ, Ko, JY, Baldassano, CF, Kontos, NJ, Baldessarini, RJ. Antidepressant treatment in bipolar versus unipolar depression. Am J Psychiatry. 2004; 161(1): 163–165. http://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.161.1.163.Google Scholar
69. Goldberg, JF, Perlis, RH, Ghaemi, SN, et al. Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: findings from the STEP–BD. Am J Psychiatry. 2007; 164(9): 1348–1355. http://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.2007.05122032.Google Scholar
70. Ghaemi, SN, Lenox, MS, Baldessarini, RJ. Effectiveness and safety of long-term antidepressant treatment in bipolar disorder. J Clin Psychiatry. 2001; 62(7): 565–569.Google Scholar
71. Ghaemi, SN, Wingo, AP, Filkowski, MA, Baldessarini, RJ. Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks. Acta Psychiatr Scand. 2008; 118(5): 347–356. Epub ahead of print Aug 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718794/pdf/nihms109410.pdf.Google Scholar
72. Sani, G, Napoletano, F, Vohringer, PA, et al. Mixed depression: clinical features and predictors of its onset associated with antidepressant use. Psychother Psychosom. 2014; 83(4): 213–221.Google Scholar