Journal Mobile Options
Table of Contents
Vol. 41, No. 3, 2008
Issue release date: April 2008
Psychopathology 2008;41:187–193

Frequency of Dysphoria and Mixed States

Bertschy G. · Gervasoni N. · Favre S. · Liberek C. · Ragama-Pardos E. · Aubry J.-M. · Gex-Fabry M. · Dayer A.
Division of Adult Psychiatry, Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Mixed states are a complex entity in the field of mood disorders. Dysphoria has been advocated as an important clinical dimension of mixed states. The objective of this work is to study the frequency of dysphoria within a population of patients with DSM-IV major depressive and/or manic episodes and to determine if it may help establish diagnostic criteria for subthreshold cases of depressive or manic mixed states. Sampling and Methods: A total of 165 patients were assessed using the Mini International Neuropsychiatric Interview complemented by a section defining dysphoria as a constellation of 3 among 4 symptoms (inner tension, irritability, aggressive behavior and hostility). Results: When classifying patients according to the number of symptoms of the opposite polarity, changes in the frequency of dysphoria revealed a clear contrast between the 2 opposite manic and depressive poles and the full mixed state (DSM-IV definition). The frequency of dysphoria was 17.5% in pure depression, 22.7% in pure mania and 73.3% in full mixed state. Two threshold effects were identified: (1) the frequency of dysphoria increased from 17.5 to 61.1% (p = 0.002) when the number of manic symptoms in DSM-IV depressed patients increased from 0 to 1, and (2) dysphoria increased from 14.3 to 69.2% (p = 0.057) when the number of depressive symptoms increased from 2 to 3 in DSM-IV manic patients. Conclusion: Dysphoria is strongly but not necessarily associated with mixed states. When used as a clinical marker for mixed states, dysphoria confirms the modern delimitations of sub-threshold mixed states by specifying the required number of symptoms of the opposite polarity (which could be lower for depressive mixed states than for manic mixed states). The study has limitations related to the inclusion of patients who are not drug-free, to the definition of dysphoria and to the sample size.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Dayer A, Aubry JM, Roth L, Ducrey S, Bertschy G: A theoretical reappraisal of mixed states: dysphoria as a third dimension. Bipolar Disord 2000;2:316–324.
  2. Berner P, Musalek M, Walter H: Psychopathological concepts of dysphoria. Psychopathology 1987;20:93–100.
  3. American Psychiatric Association (ed): Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, ed 4. Washington, American Psychiatric Association, 1994.
  4. Cassidy F, Forest K, Murry E, Carroll BJ: A factor analysis of the signs and symptoms of mania. Arch Gen Psychiatry 1998;55:27–32.
  5. Dilsaver SC, Chen YR, Shoaib AM, Swann AC: Phenomenology of mania: evidence for distinct depressed, dysphoric, and euphoric presentations. Am J Psychiatry 1999;156:426–430.
  6. Cassidy F, Pieper CF, Carroll BJ: Subtypes of mania determined by grade of membership analysis. Neuropsychopharmacology 2001;25:373–383.
  7. Sato T, Bottlender R, Kleindienst N, Moller HJ: Syndromes and phenomenological subtypes underlying acute mania: a factor analytic study of 576 manic patients. Am J Psychiatry 2002;159:968–974.
  8. Akiskal HS, Azorin JM, Hantouche EG: Proposed multidimensional structure of mania: beyond the euphoric-dysphoric dichotomy. J Affect Disord 2003;73:7–18.
  9. Gonzalez-Pinto A, Ballesteros J, Aldama A, Perez de Heredia JL, Gutierrez M, Mosquera F: Principal components of mania. J Affect Disord 2003;76:95–102.
  10. Cassidy F, Ahearn E, Carroll BJ: A prospective study of inter-episode consistency of manic and mixed subtypes of bipolar disorder. J Affect Disord 2001;67:181–185.
  11. Woods SW, Money R, Baker CB: Does the manic/mixed episode distinction in bipolar disorder patients run true over time? Am J Psychiatry 2001;158:1324–1326.
  12. Sato T, Bottlender R, Sievas M, Schroter A, Hecht S, Moller HJ: Long-term inter-episode stability of syndromes underlying mania. Acta Psychiatr Scand 2003;108:310–313.
  13. Koukopoulos A: Agitated depression as a mixed state and the problem of melancholia. Psychiatr Clin North Am 1999;22:547–564.
  14. Perugi G, Akiskal HS, Micheli C, Toni C, Madaro D: Clinical characterization of depressive mixed state in bipolar-I patients: Pisa-San Diego collaboration. J Affect Disord 2001;67:105–114.
  15. Maj M, Pirozzi R, Magliano L, Bartoli L: Agitated depression in bipolar I disorder: prevalence, phenomenology, and outcome. Am J Psychiatry 2003;160:2134–2140.
  16. Benazzi F, Koukopoulos A, Akiskal HS: Toward a validation of a new definition of agitated depression as a bipolar mixed state (mixed depression). Eur Psychiatry 2004;19:85–90.
  17. Sato T, Bottlender R, Schroter A, Moller HJ: Frequency of manic symptoms during a depressive episode and unipolar ‘depressive mixed state’ as bipolar spectrum. Acta Psychiatr Scand 2003;107:268–274.
  18. Benazzi F: Mixed depression: a clinical marker of bipolar-II disorder. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:267–274.
  19. Sato T, Bottlender R, Kleindienst N, Moller HJ: Irritable psychomotor elation in depressed inpatients: a factor validation of mixed depression. J Affect Disord 2005;84:187–196.
  20. Ducrey S, Gex-Fabry M, Dayer A, Pardos ER, Roth L, Aubry JM, Bertschy G: A retrospective comparison of inpatients with mixed and pure depression. Psychopathology 2003;36:292–298.
  21. Benazzi F: Mixed states in bipolar II disorder: should full hypomania always be required? Psychiatry Res 2004;127:247–257.
  22. Sato T, Bottlender R, Sievers M, Schroter A, Kleindienst N, Moller HJ: Evaluating the inter-episode stability of depressive mixed states. J Affect Disord 2004;81:103–113.
  23. Kraepelin E: Manic-Depressive Insanity and Paranoia. Edinburgh, Livingstone, 1921.
  24. McElroy SL, Strakowski SM, Keck PE Jr, Tugrul KL, West SA, Lonczak HS: Differences and similarities in mixed and pure mania. Compr Psychiatry 1995;36:187–194.
  25. Cassidy F, Murry E, Forest K, Carroll BJ: Signs and symptoms of mania in pure and mixed episodes. J Affect Disord 1998;50:187–201.
  26. Gonzalez-Pinto A, Aldama A, Pinto AG, Mosquera F, Perez de Heredia JL, Ballesteros J, Gutierrez M: Dimensions of mania: differences between mixed and pure episodes. Eur Psychiatry 2004;19:307–310.
  27. Swann AC, Janicak PL, Calabrese JR, Bowden CL, Dilsaver SC, Morris DD, Petty F, Davis JM: Structure of mania: depressive, irritable, and psychotic clusters with different retrospectively-assessed course patterns of illness in randomized clinical trial participants. J Affect Disord 2001;67:123–132.
  28. Akiskal HS, Benazzi F: Validating Kraepelin’s two types of depressive mixed states: ‘depression with flight of ideas’ and ‘excited depression’. World J Biol Psychiatry 2004;5:107–113.
  29. Deckersbach T, Perlis RH, Frankle WG, Gray SM, Grandin L, Dougherty DD, Nierenberg AA, Sachs GS: Presence of irritability during depressive episodes in bipolar disorder. CNS Spectr 2004;9:227–231.
  30. Pasquini M, Picardi A, Biondi M, Gaetano P, Morosini P: Relevance of anger and irritability in outpatients with major depressive disorder. Psychopathology 2004;37:155–160.
  31. Benazzi F: Major depressive disorder with anger: a bipolar spectrum disorder? Psychother Psychosom 2003;72:300–306.
  32. Benazzi F, Akiskal H: Irritable-hostile depression: further validation as a bipolar depressive mixed state. J Affect Disord 2005;84:197–207.
  33. 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;67:115–122.
  34. Segal ZV, Kennedy S, Gemar M, Hood K, Pedersen R, Buis T: Cognitive reactivity to sad mood provocation and the prediction of depressive relapse. Arch Gen Psychiatry 2006;63:749–755.
  35. Ei-Mallakh RS, Karippot A: Antidepressant-associated chronic irritable dysphoria (acid) in bipolar disorder: a case series. J Affect Disord 2005;84:267–272.
  36. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC: The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(suppl 20):22–33; quiz 34–57.
  37. American Psychiatric Association (ed): Diagnostic and Statistical Manual of Mental Disorders: DSM-III, ed 3. Washington, American Psychiatric Association, 1980.
  38. Benazzi F: Which could be a clinically useful definition of depressive mixed state? Prog Neuropsychopharmacol Biol Psychiatry 2002;26:1105–1111.
  39. Benazzi F: Bipolar family history of the hypomanic symptoms and dimensions of mixed depression. Compr Psychiatry 2005;46:399–404.
  40. Sato T, Bottlender R, Kleindienst N, Tanabe A, Moller HJ: The boundary between mixed and manic episodes in the ICD-10 classification. Acta Psychiatr Scand 2002;106:109–116.
  41. 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.
  42. Cassidy F, Ahearn E, Murry E, Forest K, Carroll BJ: Diagnostic depressive symptoms of the mixed bipolar episode. Psychol Med 2000;30:403–411.
  43. Henry C, Swendsen J, Van den Bulke D, Sorbara F, Demotes-Mainard J, Leboyer M: Emotional hyper-reactivity as a fundamental mood characteristic of manic and mixed states. Eur Psychiatry 2003;18:124–128.
  44. Akiskal HS, Hantouche EG, Bourgeois ML, Azorin JM, Sechter D, Allilaire JF, Lancrenon S, Fraud JP, Chatenet-Duchene L: Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN). J Affect Disord 1998;50:175–186.
  45. Perugi G, Maremmani I, Toni C, Madaro D, Mata B, Akiskal HS: The contrasting influence of depressive and hyperthymic temperaments on psychometrically derived manic subtypes. Psychiatry Res 2001;101:249–258.
  46. Lambert M, Schimmelmann BG, Karow A, Naber D: Subjective well-being and initial dysphoric reaction under antipsychotic drugs – concepts, measurement and clinical relevance. Pharmacopsychiatry 2003;36 (suppl 3):S181–S190.

    External Resources

  47. Voruganti L, Awad AG: Neuroleptic dysphoria: towards a new synthesis. Psychopharmacology 2004;171:121–132.
  48. Post RM, Rubinow DR, Uhde TW, Roy- Byrne PP, Linnoila M, Rosoff A, Cowdry R: Dysphoric mania: clinical and biological correlates. Arch Gen Psychiatry 1989;46:353–358.
  49. Critchlow DG, Bond AJ, Wingrove J: Mood disorder history and personality assessment in premenstrual dysphoric disorder. J Clin Psychiatry 2001;62:688–693.
  50. Bertschy G, Gervasoni N, Favre S, Liberek C, Ragama-Pardos E, Aubry JM, Gex-Fabry M, Dayer A: Phenomenology of mixed states: a principal component analysis study. Bipolar Disord, in press.
  51. Benazzi F: Bipolar disorder – focus on bipolar II disorder and mixed depression. Lancet 2007;369:935–945.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50