Atypical depressive syndromes in varying definitions

  • J. AngstEmail author
  • A. Gamma
  • F. Benazzi
  • B. Silverstein
  • V. Ajdacic–Gross
  • D. Eich
  • W. Rössler



Atypical depression (AD) exhibits distinct patterns of gender,bipolar–II disorder, genetic, and neuro–biological measures. Using prospective data from a community sample, this paper identifies criteria (and correlates) for an AD syndrome that maximizes the association with female sex and bipolar–II.


The Zurich cohort study is composed of 591 subjects selected from a population–based cohort of young adults in the canton of Zurich in Switzerland, screened in 1978 and followed with six interviews through 1999. Seven definitions of atypical depression were tested, using varying combinations of vegetative symptoms and mood reactivity.


The atypical definitions using 2 of 3 (fatigue, overeating, oversleeping) or 2 of 2 (overeating, oversleeping) vegetative symptoms showed the strongest association with gender, bipolarity, and family history of mania. The 2/3 definition was chosen for further analysis due to its high sensitivity for identifying these characteristics. This syndrome had cumulated weighted prevalence of 16.4% (males 9.7%, females 23%); when associated with major depressive episodes, 8.2% (males 3.2%, females 15.1%). AD patients were characterized by high treatment rates, severity, and work impairment, early age of onset and long illness. AD was comorbid with social phobia, binge eating, neurasthenia, migraine headache, and subjective cognitive impairment.

Key words

atypical depression bipolar–II disorder sex prevalence 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Angst J (2002) Atypical depression: a common, clinically relevant disorder. Italian J Psychopathology (8 Suppl)74:S35Google Scholar
  2. 2.
    Angst J, Gamma A, Benazzi F, Ajdacic V, Eich D, Rössler W (2003) Toward a re–definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar–II, minor bipolar disorders and hypomania. J Affect Disord 73:133–146CrossRefPubMedGoogle Scholar
  3. 3.
    Angst J, Gamma A, Sellaro R, Zhang H, Merikangas K (2002) Toward validation of atypical depression in the community: results of the Zurich cohort study. J Affect Disord 72:125–138CrossRefPubMedGoogle Scholar
  4. 4.
    Asnis GM, Keswani L, Sanderson WC (1995) Atypical depression: clinical aspects and noradrenergic function. Am J Psychiatry 152:31–36PubMedGoogle Scholar
  5. 5.
    Benazzi F (1999) Atypical depression in private practice depressed outpatients: a 203–case study. Compr Psychiatry 40:80–83PubMedGoogle Scholar
  6. 6.
    Benazzi F (2000a) Depression with DSM–IV atypical features: a marker for bipolar II disorder. Eur Arch Psychiatry Clin Neurosci 250:53–55Google Scholar
  7. 7.
    Benazzi F (2000b) Early–onset versus late–onset atypical depression: unipolar and bipolar II. J Affect Disord 61:95–99CrossRefGoogle Scholar
  8. 8.
    Benazzi F (2000c) Late–life atypical major depressive episode. a 358–case study in outpatients. Am J Geriatr Psychiatry 8:117–122Google Scholar
  9. 9.
    Benazzi F (2001) Bipolar II depression in late life: prevalence and clinical features in 525 depressed outpatients. J Affect Disord 66:13–18CrossRefPubMedGoogle Scholar
  10. 10.
    Benazzi F (2002a) Can only reversed vegetative symptoms define atypical depression? Eur Arch Psychiatry Clin Neurosci 252:288–293Google Scholar
  11. 11.
    Benazzi F (2002b) Should mood reactivity be included in the DSM–IV atypical features specifier? Eur Arch Psychiatry Clin Neurosci 252:135–140Google Scholar
  12. 12.
    Benazzi F (2003) Testing DSM–IV definition of atypical depression. Ann Clin Psychiatry 15:9–16CrossRefPubMedGoogle Scholar
  13. 13.
    Bruder GE, Quitkin FM, Stewart JW, Martin C, Voglmaier MM, Harrison WM (1989) Cerebral laterality and depression: Perceptual asymmetry in diagnostic subtypes before and after antidepressant treatment. J Abnorm Psychol 98:177–186CrossRefPubMedGoogle Scholar
  14. 14.
    Bruder GE, Stewart JW, McGrath PJ, Guoguang JM, Wexler BE, Quitkin FM (2002) Atypical depression: Enhanced right hemispheric dominance for perceiving emotional chimeric faces. J Abnorm Psychol 111:446–454CrossRefPubMedGoogle Scholar
  15. 15.
    Davidson IA, Dewey ME, Copeland JRM (1988) The relationship between mortality and mental disorder: evidence from the Liverpool longitudinal study. Int J Ger Psychiatry 3:95–98Google Scholar
  16. 16.
    Davidson J, Pelton S (1986) Forms of atypical depression and their response to antidepressant drugs. Psychiatry Res 17:87–95CrossRefPubMedGoogle Scholar
  17. 17.
    Derogatis LR (1977) SCL–90. Administration, scoring and procedures manual–I for the R (revised) version and other instruments of the Psychopathology Rating Scale Series. Johns Hopkins University School of Medicine, ChicagoGoogle Scholar
  18. 18.
    Fotiou F, Fountoulakis KN, Iacovides A, Kaprinis G (2003) Pattern– reversed visual evoked potentials in subtypes of major depression. Psychiatry Res 118:259–271CrossRefPubMedGoogle Scholar
  19. 19.
    Geracioti TD, Loosen PT, Orth DN (1997) Low cerebrospinal fluid corticotropin–releasing hormone concentrations in eucortisolemic depression. Biol Psychiatry 42:166–174Google Scholar
  20. 20.
    Harrison WM, Cooper TB, Stewart JW, Quitkin FM, McGrath PJ, Liebowitz MR, Rabkin JR, Markowitz JS, Klein DF (1984) The tyramine challenge test as a marker for melancholia. Arch Gen Psychiatry 41:681–685PubMedGoogle Scholar
  21. 21.
    Henkel V, Mergl R, Coyne JC, Kohnen R, Allgaier AK, Ruehl E, Moeller HJ, Hegerl U (2004) Depression with atypical features in a sample of primary care outpatients: prevalence, specific characteristics and consequences. J Affect Disord 83:237–242CrossRefPubMedGoogle Scholar
  22. 22.
    Himmelhoch JM, Thase ME (1989) The vagaries of the concept of atypical depression. In: Howells JG (ed) Modern perspectives in the psychiatry of the affective disorders. Plenum Press, New York, pp 223–242Google Scholar
  23. 23.
    Hordern A (1965) The antidepressant drugs. N Eng J Med 272:1159–1169Google Scholar
  24. 24.
    Horwath E, Johnson J, Weissman MM, Hornig CD (1992) The validity of major depression with atypical features based on a community study. J Affect Disord 26:117–126CrossRefPubMedGoogle Scholar
  25. 25.
    Kendler KS, Eaves LJ, Walters EE, Neale MC, Heath AC, Kessler RC (1996) The identification and validation of distinct depressive syndromes in a population–based sample of female twins. Arch Gen Psychiatry 53:391–399PubMedGoogle Scholar
  26. 26.
    Korszun A, Moskvina V, Brewster S, Craddock N, Ferrero F, Gill M, Jones JR, Jones LA, Maier W, Mors O (2004) Familiality of symptom dimensions in depression. Arch Gen Psychiatry 61:468–474PubMedGoogle Scholar
  27. 27.
    Levitan RD, Lesage A, Parikh SV, Goering P, Kennedy SH (1997) Reversed neurovegetative symptoms of depression: a community study of Ontario. Am J Psychiatry 154:934–940PubMedGoogle Scholar
  28. 28.
    Liebowitz MR, Gorman JM, Fyer AJ, Campeas R, Levin AP, Sandberg D, Hollander E, Papp L, Goetz D (1988) Pharmacotherapy of social phobia: a placebo controlled comparison of phenelzine and atenolol. J Clin Psychiatry 49:252–257PubMedGoogle Scholar
  29. 29.
    Matza LS, Revicki DA, Davidson JR, Stewart JW (2003) Depression with atypical features in the national comorbidity survey. Arch Gen Psychiatry 60:817–826PubMedGoogle Scholar
  30. 30.
    McGinn LK, Asnis GM, Rubinson E (1996) Biological and clinical validation of atypical depression. Psychiatry Res 60:191–198 CrossRefPubMedGoogle Scholar
  31. 31.
    Mountjoy CQ, Roth M, Garside RF, Leitch IM (1977) A clinical trial of phenelzine in anxiety, depressive and phobic neuroses. Br J Psychiatry 131:486–492PubMedGoogle Scholar
  32. 32.
    Nierenberg AA, Alpert JE, Pava J, Rosenbaum JF, Fava M (1998) Course and treatment of atypical depression. J Clin Psychiatry 59(Suppl)18:5–9PubMedGoogle Scholar
  33. 33.
    Parker G, Roy K, Mitchell P, Wilhelm K, Malhi G, Hadzi–Pavlovic D (2002) Atypical depression: A reappraisal. Am J Psychiatry 159:1470–1479Google Scholar
  34. 34.
    Parker G, Roy K, Wilhelm K, Mitchell P, Hadzi–Pavlovic D (2000) The nature of bipolar depression: implications for the definition of melancholia. J Affect Disord 59:217–224CrossRefPubMedGoogle Scholar
  35. 35.
    Perugi G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A, Vignoli S, Berni E (1998) The high prevalence of “soft” bipolar (II) features in atypical depression. Compr Psychiatry 39:63–71CrossRefPubMedGoogle Scholar
  36. 36.
    Posternak MA, Zimmermann M (2002) The prevalence of atypical features across mood, anxiety, and personality disorders. Compr Psychiatry 43:253–262CrossRefPubMedGoogle Scholar
  37. 37.
    Quitkin F, McGrath P, Stewart J, Harrison W, Wager SG, Nunes E, Rabkin JG, Tricamo E, Markowitz J, Klein DF (1989) Phenelzine and imipramine in mood reactive depressives: further delineation of the syndrome of atypical depression. Arch Gen Psychiatry 46:787–793PubMedGoogle Scholar
  38. 38.
    Quitkin FM, Harrison W, Stewart JW, McGrath PJ, Tricamo E, Ocepek–Welikson K, Rabkin JG, Wager SG, Nunes E, Klein DF (1991) Response to phenelzine and imipramine in placebo nonresponders with atypical depression: a new application of the crossover design. Arch Gen Psychiatry 48:319–323PubMedGoogle Scholar
  39. 39.
    Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Tricamo E, Wager SG, Ocepek–Welikson K, Nunes E, Rabkin JG, Klein DF (1990) Atypical depression, panic attacks, and response to imipramine and phenelzine: a replication. Arch Gen Psychiatry 47:935–941PubMedGoogle Scholar
  40. 40.
    Quitkin FM, Rabkin JG, Stewart JW, McGrath PJ, Harrison W, Davies M, Goetz R, Puig–Antich J (1985) Sleep of atypical depressives. J Affect Disord 8:61–67CrossRefPubMedGoogle Scholar
  41. 41.
    Quitkin FM, Stewart JW, McGrath PJ, Liebowitz MR, Harrison WM, Tricamo E, Klein DF, Rabkin JG, Markowitz JS, Wager SG (1988) Phenelzine versus imipramine in the treatment of probable atypical depression: defining syndrome boundaries of selective MAOI responders. Am J Psychiatry 145:306–311PubMedGoogle Scholar
  42. 42.
    Rabkin JG, Stewart JW, Quitkin FM, McGrath PJ, Harrison WM, Klein DF (1996) Should atypical depression be included in DSMIV? In: Widiger TA, Frances AJ, Pincus HA, Ross R, First MB, Davies WW (eds) DSM–IV sourcebook. Vol. 2 American Psychiatric Press, Washington DC, pp 239–260Google Scholar
  43. 43.
    Ravaris CL, Nies A, Robinson DS, Ives JO, Lamborn KR, Korson L (1976) A multiple dose, controlled study of phenelzine in depression– anxiety states. Arch Gen Psychiatry 33:347–350PubMedGoogle Scholar
  44. 44.
    Robertson HA, Lam RW, Stewart JN, Yatham LN, Tam EM, Zis AP (1996) Atypical depressive symptoms and clusters in unipolar and bipolar depression. Acta Psychiatr Scand 94:421–427PubMedGoogle Scholar
  45. 45.
    Robinson DS, Nies A, Ravaris CL, Lamborn KR (1973) The monoamine oxidase inhibitor, phenelzine, in the treatment of depressive–anxiety states. A controlled clinical trial. Arch Gen Psychiatry 29:407–413PubMedGoogle Scholar
  46. 46.
    Sargant W (1960) Some newer drugs in the treatment of depression and their relation to other somatic treatments. Psychosomatics 1:14–17Google Scholar
  47. 47.
    Silverstein B (1999) Gender difference in the prevalence of clinical depression: the role played by depression associated with somatic symptoms. Am J Psychiatry 156:480–482PubMedGoogle Scholar
  48. 48.
    Sotsky SM, Simmens SJ (1999) Pharmacotherapy response and diagnostic validity in atypical depression. J Affect Disord 54:237–247CrossRefPubMedGoogle Scholar
  49. 49.
    Stewart JW, McGrath PJ, Rabkin JG, Quitkin FM (1993) Atypical depression. A valid clinical entity? Psychiatr Clin North Am 16:479–495PubMedGoogle Scholar
  50. 50.
    Stewart JW, Tricamo E, McGrath P, Quitkin FM (1997) Prophylactic efficacy of phenelzine and imipramine in chronic atypical depression: likelihood of recurrence on discontinuation after 6 months’ remission. Am J Psychiatry 154:31–36PubMedGoogle Scholar
  51. 51.
    Sullivan PF, Kessler RC, Kendler KS (1998) Latent class analysis of lifetime depressive symptoms in the national comorbidity survey. Am J Psychiatry 155:1398–1406PubMedGoogle Scholar
  52. 52.
    Sullivan PF, Prescott CA, Kendler KS (2002) The subtypes of major depression in a twin registry. J Affect Disord 68:273–284CrossRefPubMedGoogle Scholar
  53. 53.
    Thase ME, Carpenter L, Kupfer DJ, Frank E (1991) Clinical significance of reversed vegetative subtypes of recurrent major depression. Psychopharmacol Bull 27:17–22PubMedGoogle Scholar
  54. 54.
    Thase ME, Himmelhoch JM, Mallinger AG, Jarrett DB, Kupfer DJ (1989) Sleep EEG and DST findings in anergic bipolar depression. Am J Psychiatry 146:329–333PubMedGoogle Scholar
  55. 55.
    West ED, Dally PJ (1959) Effect of iproniazid in depressive syndromes. Brit Med J 1:1491–1494Google Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  • J. Angst
    • 1
    Email author
  • A. Gamma
    • 1
  • F. Benazzi
    • 2
    • 3
  • B. Silverstein
    • 4
  • V. Ajdacic–Gross
    • 1
  • D. Eich
    • 1
  • W. Rössler
    • 1
  1. 1.Zurich University Psychiatric HospitalZurichSwitzerland
  2. 2.E. Hecker Outpatient Psychiatry CentreRavennaItaly
  3. 3.Department of PsychiatryNational Health ServiceForliItaly
  4. 4.Department of PsychologyCity College, City University of New YorkNew YorkUSA

Personalised recommendations