Annals of Clinical Psychiatry

, Volume 15, Issue 1, pp 9–16 | Cite as

Testing DSM-IV Definition of Atypical Depression

  • Franco BenazziEmail author


The definition of atypical depression (AD) has recently seen a rebirth of studies, as the evidence supporting DSM-IV atypical features criteria is weak. Study aim was to test the validity of DSM-IV definition of AD. Consecutive 202 major depressive disorder (MDD) and 281 bipolar II outpatients were interviewed, during a major depressive episode (MDE), with the Structured Clinical Interview for DSM-IV. The relationships of DSM-IV AD versus variables often reported to distinguish AD and non-AD (gender, age, onset, bipolar II, axis I comorbidity, MDE severity, residual MDE symptoms, depressive mixed state), and versus bipolar family history, were tested. Each DSM-IV AD symptom's relationship with the variables found significantly associated to DSM-IV AD was then tested, in order to assess the degree of concordance among all AD symptoms. Associations were tested by univariate logistic regression (STATA 7). Frequency of DSM-IV AD was 42.8%. DSM-IV AD was significantly more common in bipolar II versus MDD (53.7% vs. 27.7%, p = 0.0000). DSM-IV AD significant associations were the following: bipolar II, female gender, lower age, lower age of onset, residual MDE symptoms, axis I comorbidity, psychotic features, depressive mixed state, and bipolar family history. Testing associations of each DSM-IV AD symptom versus the variables found associated to DSM-IV AD showed high concordance. All AD symptoms were significantly associated with DSM-IV AD, and with most study variables. Results support the current DSM-IV definition of AD.

atypical depression atypical features DSM-IV bipolar II disorder 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association; 1994Google Scholar
  2. 2.
    Rabkin JG, Stewart JW, Quitkin FM, McGrath PJ, Harrison WM, Klein DF: Should atypical depression be included in DSM-IV?. In: DSM-IV Sourcebook, Vol 2. Washington, DC: American Psychiatric Association; 1996:239-260Google Scholar
  3. 3.
    Robins E, Guze SB: Establishment of diagnostic validity in psychiatric illness: Its application to schizophrenia. Am J Psychiatry 1970; 126:983-987Google Scholar
  4. 4.
    Akiskal HS: Classification, diagnosis and boundaries of bipolar disorders: A review. In: Maj M, Akiskal HS, Lopez-Ibor JJ, Sartorius N, eds. Bipolar Disorder. Chichester, UK: Wiley, 2002:1-52Google Scholar
  5. 5.
    Akiskal HS: Validating ‘hard’ and ‘soft’ phenotypes within the bipolar spectrum: Continuity or discontinuity? J Affect Disord 2003; 73:1-5Google Scholar
  6. 6.
    Kendler KS: The nosologic validity of paranoia (simple delusional disorder). Arch Gen Psychiatry 1980; 37:699-706Google Scholar
  7. 7.
    Kendler KS: Toward a scientific psychiatric nosology. Strengths and limitations. Arch Gen Psychiatry 1990; 47:969-973Google Scholar
  8. 8.
    McGrath PJ, Stewart JW, Janal MN, Petkova E, Quitkin FM, Klein DF: A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry 2000; 157:344-350Google Scholar
  9. 9.
    Sotsky SM, Simmens SJ: Pharmacotherapy response and diagnostic validity in atypical depression. J Affect Disord 1999; 54:237-247Google Scholar
  10. 10.
    Levitan RD, Lesage A, Parikh SV, Goering P, Kennedy SH: Reversed neurovegetative symptoms of depression: A community study of Ontario. Am J Psychiatry 1997; 154:934-940Google Scholar
  11. 11.
    Sullivan PF, Kessler RC, Kendler KS: Latent class analysis of lifetime depressive symptoms in the national comorbidity survey. Am J Psychiatry 1998; 155:1398-1406Google Scholar
  12. 12.
    Williamson DE, Birmaher B, Brent DA, Balach L, Dahl RE, Ryan ND: Atypical symptoms of depression in a sample of depressed child and adolescent outpatients. J Am Acad Child Adolesc Psychiatry 2000; 39:1253-1259Google Scholar
  13. 13.
    Kendler KS, Eaves LJ, Walters EE, Neale MC, Heath AC, Kessler RC: The identification and validation of distinct depressive syndromes in a population-based sample of female twins. Arch Gen Psychiatry 1996; 53:391-399Google Scholar
  14. 14.
    Horwath E, Johnson J, Weissman MM, Horning CD: The validity of major depression with atypical features based on a community study. J Affect Disord 1992; 26:117-126Google Scholar
  15. 15.
    Benazzi F: Prevalence of bipolar II disorder in atypical depression. Eur Arch Psychiatry Clin Neurosci 1999; 249:62-65Google Scholar
  16. 16.
    Benazzi F: Prevalence and clinical features of atypical depression in depressed outpatients: A 467-case study. Psychiatry Res 1999; 86:259-265Google Scholar
  17. 17.
    Benazzi F: Atypical depression in private practice depressed outpatients: A 203-case study. Compr Psychiatry 1999; 40:80-83Google Scholar
  18. 18.
    Benazzi F: Chronic atypical major depressive episode in private practice: Unipolar and bipolar II. Acta Psychiatr Scand 1999; 100:418-423Google Scholar
  19. 19.
    Benazzi F: Is atypical depression a moderate severity depression? A 536-case study. J Psychiatry Neurosci 1999; 24:244-247Google Scholar
  20. 20.
    Benazzi F: Early-onset versus late-onset atypical depression: Unipolar and bipolar II. J Affect Disord 2000; 61:95-99Google Scholar
  21. 21.
    Benazzi F: Late-life atypical major depressive episode: A 358-case study in outpatients. Am J Geriatr Psychiatry 2000; 8:117-122Google Scholar
  22. 22.
    Benazzi F: Depression with DSM-IV atypical features: A marker for bipolar II disorder. Eur Arch Psychiatry Clin Neurosci 2000; 250:53-55Google Scholar
  23. 23.
    Angst J: The emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord 1998; 50:143-151Google Scholar
  24. 24.
    Perugi G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A, Vignoli S, Bemi E: The high prevalence of “soft” bipolar (II) features in atypical depression. Compr Psychiatry 1998; 39:63-71Google Scholar
  25. 25.
    Angst J, Gamma A, Sellaro R, Zhang H, Merikangas K: Toward validation of atypical depression in the community: Results of the Zurich cohort study. J Affect Disord 2002; 72:125-138Google Scholar
  26. 26.
    Akiskal HS, Bourgeois ML, Angst J, Post R, Moller H-J, Hirschfeld R: Re-evaluating the prevalence and diagnostic composition within the broad clinical spectrum of bipolar disorders. J Affect Disord 2000; 59(Suppl. 1):S5-S30Google Scholar
  27. 27.
    Benazzi F: Prevalence of bipolar II disorder in outpatient depression: A 203-case study in private practice. J Affect Disord 1997; 43:163-166Google Scholar
  28. 28.
    Benazzi F: Bipolar II depression in late life: Prevalence and clinical features in 525 depressed outpatients. J Affect Disord 2001; 66:13-18Google Scholar
  29. 29.
    Benazzi F, Akiskal HS: Refining the evaluation of bipolar II: Beyond the strict SCID-CV guidelines for hypomania. J Affect Disord 2003; 73:33-38Google Scholar
  30. 30.
    Hantouche EG, Akiskal HS, Lencrenon S, Allilaire J-F, Sechter D, Azorin J-M, Bourgeois M, Fraud J-P, Chatenet-Duchene L: Systematic clinical methodology for validating bipolar-II disorder: Data in mid-stream from a french national multi-site study (EPIDEP). J Affect Disord 1998; 50:163-173Google Scholar
  31. 31.
    Cassano GB, Akiskal HS, Savino M, Musetti L, Perugi G, Soriani A: Proposed subtypes of bipolar II and related disorders: With hypomanic episodes (or cyclothymia) and with hyperthymic temperament. J Affect Disord 1992; 26:127-140Google Scholar
  32. 32.
    Angst J: Comorbidity of mood disorders: A longitudinal prospective study. Br J Psychiatry 1996; 168(Suppl. 30):31-37Google Scholar
  33. 33.
    Angst J, Gamma A, Benazzi F, Ajdacic V, Eich D, Rossler W: Toward a re-definition of subthreshold bipolarity: Epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. J Affect Disord 2003; 73:133-146Google Scholar
  34. 34.
    Serretti A, Lattuada E, Cusin C, Macciardi F, Smeraldi E: Analysis of depressive symptomatology in mood disorders. Depress Anxiety 1998; 8:80-85Google Scholar
  35. 35.
    Mitchell PB, Wilhelm K, Parker G, Austin M-P, Rutgers P, Malhi GS: The clinical features of bipolar depression: A comparison with matched major depressive disorder patients. J Clin Psychiatry 2001; 62:212-216Google Scholar
  36. 36.
    Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, Keller M, Warshaw M, Clayton P, Goodwin F: Switching from “unipolar” to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 1995; 52:114-123Google Scholar
  37. 37.
    Goodwin FK, Jamison KR: Manic-Depressive Illness. New York: Oxford University Press; 1990Google Scholar
  38. 38.
    Akiskal HS: Mood disorders: Clinical features. In: Sadock BJ, Sadock VA, eds. Kaplan & Sadock's Comprehensive Textbook of Psychiatry, 7th edn on CD-ROM. Philadelphia: Lippincott Williams & Wilkins; 2000: 28294-29391Google Scholar
  39. 39.
    McGrath PJ, Stewart JW, Harrison WM, Ocepek-Welikson K, Rabkin JG, Nunes EN, Wager SG, Tricamo E, Quitkin FM, Klein DF: Predictive value of symptoms of atypical depression for differential drug treatment outcome. J Clin Psychopharmacol 1992; 12: 197-202Google Scholar
  40. 40.
    Robertson HA, Lam RW, Stewart JN, Yatham LN, Tam EM, Zis AP: Atypical depressive symptoms and clusters in unipolar and bipolar depression. Acta Psychiatr Scand 1996; 94:421-427Google Scholar
  41. 41.
    Posternak MA, Zimmerman M: Partial validation of the atypical features subtype of major depressive disorder. Arch Gen Psychiatry 2002; 59:70-76Google Scholar
  42. 42.
    Parker G, Roy K, Wilhelm K, Mitchell P, Hadzi-Pavlovic D: The nature of bipolar depression: Implications for the definition of melancholia. J Affect Disord 2000; 59:217-224Google Scholar
  43. 43.
    Coryell W, Endicott J, Maser JD, Keller MB, Leon AC, Akiskal HS: Long-term stability of polarity distinctions in the affective disorders. Am J Psychiatry 1995; 152:385-390Google Scholar
  44. 44.
    Coryell W: Bipolar II disorder: The importance of hypomania. In: Goldberg JF, Harrow M, eds. Bipolar Disorders. Clinical Course and Outcome. Washington, DC: American Psychiatric Press; 1999:219-236Google Scholar
  45. 45.
    McMahon FJ, Simpson SG, McInnis MG, Badner JA, MacKinnon DF, DePaulo JR: Linkage of bipolar disorder to chromosome 18q and the validity of bipolar II disorder. Arch Gen Psychiatry 2001; 58:1025-1031Google Scholar
  46. 46.
    American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4 edn, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000Google Scholar
  47. 47.
    Parker G: Classifying depression: Should paradigms lost be regained? Am J Psychiatry 2000; 157:1195-1203Google Scholar
  48. 48.
    Nierenberg AA, Alpert JE, Pava J, Rosenbaum JF, Fava M: Course and treatment of atypical depression. J Clin Psychiatry 1998; 59(Suppl. 18):5-9Google Scholar
  49. 49.
    Benazzi F: Should mood reactivity be included in the DSM-IV atypical features specifier? Eur Arch Psychiatry Clin Neurosci 2002; 252:135-140Google Scholar
  50. 50.
    Posternak MA, Zimmerman M: Symptoms of atypical depression. Psychiatry Res 2001; 104:175-181Google Scholar
  51. 51.
    Parker G, Roy K, Mitchell P, Wilhelm K, Malhi G, Hadzi-Pavlovic D: Atypical depression: A reappraisal. Am J Psychiatry 2002; 159:1470-1479Google Scholar
  52. 52.
    Ghaemi SN: Dr. Ghaemi replies. High prevalence of bipolar spectrum disorders, by Benazzi F. J Clin Psychiatry 2001; 62:735-736Google Scholar
  53. 53.
    Akiskal HS, Pinto O: The evolving bipolar spectrum: Prototypes I, II, III, and IV. Psychiatr Clin North Am 1999; 22:517-534Google Scholar
  54. 54.
    Ghaemi SN, Boiman EE, Goodwin FK: Diagnosing bipolar disorder and the effect of antidepressants: A naturalistic study. J Clin Psychiatry 2000; 61:804-808Google Scholar
  55. 55.
    Goldberg JF, Kocsis JH: Depression in the course of bipolar disorder. In: Goldberg JF, Harrow M, eds. Bipolar Disorders. Clinical Course and Outcome. Washington, DC: American Psychiatric Press; 1999Google Scholar
  56. 56.
    Post RM, Nolen WA, Kupka RW, Denicoff KD, Leverich GS, Keck PE, McElroy SL, Rush AJ, Suppes T, Altshuler LL, Frye MA, Grunze H, Walden J: The Stanley Foundation Bipolar Network. 1. Rationale and methods. Br J Psychiatry 2001; 178:s169-s176Google Scholar
  57. 57.
    Benazzi F: Borderline personality disorder and bipolar II disorder in private practice depressed outpatients. Compr Psychiatry 2000; 41:106-110Google Scholar
  58. 58.
    First MB, Spitzer RL, Gibbon M, Williams JBW: Structured Clinical Interview for DSM-IV Axis I disorders-Clinician Version (SCID-CV). Washington, DC: American Psychiatric Press; 1997Google Scholar
  59. 59.
    Simpson SG, McMahon FJ, McInnis MG, MacKinnon DF, Edwin D, Folstein SE, DePaulo JR: Diagnostic reliability of bipolar II diagnosis. Arch Gen Psychiatry 2002; 59:736-740Google Scholar
  60. 60.
    Brugha TS, Jenkins R, Taub N, Meltzer H, Bebbington PE: A general population comparison of the Composite International Diagnostic Interview (CIDI) and the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Psychol Med 2001; 31:1001-1013Google Scholar
  61. 61.
    Dunner DL, Tay KL: Diagnostic reliability of the history of hypomania in bipolar II patients and patients with major depression. Compr Psychiatry 1993; 34:303-307Google Scholar
  62. 62.
    Koukopoulos A, Koukopoulos A: Agitated depression as a mixed state and the problem of melancholia. Psychiatr Clin North Am 1999; 22:547-564Google Scholar
  63. 63.
    Dunner DL: Diagnostic revisions for DSM-IV. In: Goodnick PL, ed. Mania. Clinical and Research Perspectives. Washington, DC: American Psychiatric Press; 1998:3-10Google Scholar
  64. 64.
    Akiskal HS, Djenderedjian AH, Rosenthal RH, Khani MK: Cyclothymic disorder: Validating criteria for inclusion in the bipolar affective group. Am J Psychiatry 1977; 134:1227-1233Google Scholar
  65. 65.
    Akiskal HS: The prevalent clinical spectrum of bipolar disorders: Beyond DSM-IV. J Clin Psychopharmacol 1996; 16(Suppl. 1):4S-14SGoogle Scholar
  66. 66.
    Benazzi F: Is 4 days the minimum duration of hypomania in bipolar II disorder? Eur Arch Psychiatry Clin Neurosci 2001; 251:32-34Google Scholar
  67. 67.
    Weissman MM, Wickramaratne P, Adams P, Wolk S, Verdeli H, Olfson M: Brief screening for family psychiatric history. The family history screen. Arch Gen Psychiatry 2000; 57:675-682Google Scholar
  68. 68.
    Benazzi F: Sensitivity and specificity of clinical markers for the diagnosis of bipolar II disorder. Compr Psychiatry 2001; 42:461-465Google Scholar
  69. 69.
    Benazzi F: Bipolar II depressive mixed state: Finding a useful definition. Compr Psychiatry 2003; 44:21-27Google Scholar
  70. 70.
    Akiskal HS, Benazzi F: Family history validation of the bipolar nature of depressive mixed states. J Affect Disord 2003; 73:113-122Google Scholar
  71. 71.
    Benazzi F, Akiskal HS: Clinical and factor analytic validation of depressive mixed state in outpatient private practice. Curr Opi Psychiatry (in press)Google Scholar
  72. 72.
    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; 67:115-122Google Scholar
  73. 73.
    Agosti V, Stewart JW: Atypical and non-atypical subtypes of depression: Comparison of social functioning, symptoms, course of illness, co-morbidity and demographic features. J Affect Disord 2001; 65:75-79Google Scholar
  74. 74.
    Sullivan PF, Prescott CA, Kendler KS: The subtypes of major depression in a twin registry. J Affect Disord 2002; 68:273-284Google Scholar
  75. 75.
    Ghaemi SN, Ko JY, Goodwin FK: “Cade's disease” and beyond: Misdiagnosis, antidepressant use, and a proposed definition for bipolar spectrum disorder. Can J Psychiatry 2002; 47:125-134Google Scholar
  76. 76.
    Asnis GM, McGinn LK, Sanderson WC: Atypical depression: Clinical aspects and noradrenergic function. Am J Psychiatry 1996; 152:31-36Google Scholar
  77. 77.
    American Psychiatric Association: Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159(Suppl):1-50Google Scholar
  78. 78.
    Baldessarini RJ: A plea for integrity of the bipolar disorder concept. Bipolar Disord 2000; 2:3-7Google Scholar
  79. 79.
    McMahon FJ, Stine OC, Chase GA, Meyers DA, Simpson SG, DePaulo JR: Influence of clinical subtype, sex, and lineality on age at onset of major affective disorder in a family sample. Am J Psychiatry 1994; 151:210-215Google Scholar

Copyright information

© American Academy of Clinical Psychiatrists 2003

Authors and Affiliations

  1. 1.Outpatient Psychiatry CenterUniversity of California at San Diego (USA
  2. 2.Collaborating Center in Ravenna and ForliItaly
  3. 3.Department of PsychologyUniversity of BolognaBolognaItaly
  4. 4.Department of PsychiatryNational Health ServiceForliItaly

Personalised recommendations