Research reportToward validation of atypical depression in the community: results of the Zurich cohort study
Introduction
Although the concept of atypical depression has been widely recognized since first described by West and Dally (1959) 40 years ago, there is still no consensus regarding the specific diagnostic criteria, nor on its clinical significance. Nevertheless, systematic review of the evidence for the validity of atypical depression reveals some specificity in family (Stewart et al., 1993, Stewart et al., 1997) and twin studies (Kendler et al., 1996), differential treatment response (Dally and Rohde, 1961, Robinson et al., 1973, Tyrer, 1976, Ravaris et al., 1976, Mountjoy et al., 1977, Davidson et al., 1988, Liebowitz et al., 1988, Quitkin et al., 1988, Quitkin et al., 1989, Quitkin et al., 1990, Quitkin et al., 1991, Thase et al., 1991, Sotsky and Simmens, 1999), biologic correlates (Quitkin et al., 1985, Harrison et al., 1984, Bruder et al., 1989, Asnis et al., 1995, McGinn et al., 1996, Geracioti et al., 1997), course (Davidson et al., 1989, Thase et al., 1991, Horwath et al., 1992, Stewart et al., 1993, Benazzi, 1999a), stability (Kendler et al., 1996, Nierenberg et al., 1996) and co-occurrence with other syndromes or disorders (Tam et al., 1997, Perugi et al., 1998, Benazzi, 1999a, Benazzi, 2000, Benazzi and Rihmer, 2000).
A major impediment to the validity of atypical depression is the lack of consistency in the definitions employed by studies that have investigated the clinical significance of this depressive subtype. Comprehensive reviews of the definitions and evidence for an atypical subtype of depression are presented by Stewart et al. (1993), Lam and Stewart (1996), Rabkin et al. (1996) and Fountoulakis et al. (1999). The two major elements of atypical depression that have been considered include: reverse neurovegetative symptoms (i.e. over-sleeping and/or over-eating, or weight gain); and reactivity of mood (i.e. capacity to be cheered up by positive events). Other criteria that have been considered as manifestations of atypical depression are ‘leaden paralysis,’ (i.e. severe lethargy and fatigue, heavy weighted down feeling in arms or legs) and the trait of rejection sensitivity (excessive reaction to perceived rejection in social relationships) (Quitkin et al., 1979).
The first operational definition of atypical depression included reactivity of mood, accompanied by increased sleep, loss of energy, increased appetite or weight, and sensitivity to interpersonal rejection (Quitkin et al., 1979). Based in part on the critical review of the current knowledge base by Rabkin et al. (1996), the DSM-IV adopted the following criteria for atypical depression: mood reactivity plus two of the four symptom criteria described above. Despite the fairly well-established evidence for an atypical subtype of depression, the reliability and validity of the specific inclusion criteria such as mood reactivity and leaden paralysis have not been studied systematically (Thase et al., 1991, McGinn et al., 1996).
The diagnostic criterion of ‘rejection sensitivity’ is required to represent a long-standing characteristic that does not solely occur in conjunction with particular episodes of atypical depression. As such, it would be more appropriately assessed as part of Axis II personality disorders, particularly since it represents a quality of interpersonal relationships (Klein, 1995). However, as evidence for the substantial overlap between symptom clusters represented on Axis I and the enduring traits represented on Axis II emerges, future classification may well integrate these two axes.
The criterion of reverse neurovegetative signs has been evaluated in several studies using either informative study designs or statistical classification methods. This research has yielded consistent evidence that those with appetite and/or weight increase and hypersomnia comprise a distinct subgroup of depression (Young et al., 1986, Grove et al., 1987, Eaton et al., 1989a, Kendler et al., 1996).
Substantial clinical research has also yielded indirect support for an association between atypical depression and the bipolar subtype of affective disorder, particularly subthreshold bipolar disorder (Akiskal et al., 1983, Ebert and Barocka, 1991, Perugi et al., 1998, Benazzi, 1999b). Several investigators have shown that the symptoms of bipolar vs. unipolar atypical depression are virtually identical (Robertson et al., 1996). Likewise, patients with bipolar spectrum temperament (i.e. cyclothymic and hyperthymic) have been shown to manifest atypical depression more frequently than typical depression (Perugi et al., 1998). Moreover, a strong association between depression with reverse neurovegetative signs and bipolar depression was found in a community study (Levitan et al., 1997b). Several other studies have reported associations between the atypical subtype with other nonaffective disorders including panic disorder (Horwath et al., 1992, Perugi et al., 1998), social phobia (Alpert et al., 1997, Perugi et al., 1998), obsessive–compulsive disorder (Perugi et al., 1998), somatization disorder (Horwath et al., 1992), body dysmorphic disorder (Perugi et al., 1998), bulimia (Levitan et al., 1994, Levitan et al., 1997a, Levitan et al., 1998) and drug abuse/dependence (Horwath et al., 1992).
Compared to nonatypical depression, the course of atypical depression seems to be characterized by an earlier onset, longer episodes and higher chronicity. In a retrospective evaluation of the stability of reverse neurovegetative signs, Levitan et al. (1997b) found that individuals who tended to fluctuate between typical and atypical subtypes across episodes tended to comprise a distinct ‘atypical’ group. In contrast, those with stable atypical features more closely resembled typical depressives in terms of comorbidity rates, disability and health care utilization.
Section snippets
Aims
Despite the compelling evidence for the clinical significance of the concept of atypical depression, there is a striking absence of both systematic validation of the inclusion criteria for atypical depression, as well as a lack of information from community-based studies on the prevalence of atypical depression using full diagnostic criteria. Therefore, the major goals of this paper are:
- 1.
to compare a nonhierarchical definition of atypical depression with the hierarchical concept of DSM-IV;
- 2.
to
Clinical characteristics by different definitions of atypical depression
Our initial analyses evaluated the clinical significance of the DSM-IV definition of the atypical features specifier. Since there was no a priori evidence for the requirement of mood reactivity as the core diagnostic feature, we included mood reactivity as one of the features of atypical depression rather than a required core feature. Similar to the DSM-IV that require mood reactivity plus two of the other four atypical features, we required three of the five features for our definition of
Discussion
The main finding of the present study is the magnitude and validity of the atypical subtype of depression in the community. This subtype was found to meet the traditional indicators of validity in terms of the inclusion criteria, delimitation from other disorders, clinical severity, course and stability. This supplements the abundant clinical research on differential treatment response on which the original identification of this subtype was based (Mountjoy et al., 1977, Ravaris et al., 1976,
Acknowledgements
This work was supported by Grant 32-33980-92 of the Swiss National Science Foundation and Research Scientist Development Award K02-MH00499 Mental Health Administration of the United States Public Health Service to Dr. Merikangas. We would like to thank Drs. Donald F. Klein, Fred Quitkin and Jonathan Stewart, New York State Psychiatric Institute, for their productive and critical comments.
References (81)
- et al.
Bipolar outcome in the course of depressive illness. Phenomenologic, familial, and pharmacologic predictors
J. Affect. Disord.
(1983) The emerging epidemiology of hypomania and bipolar II disorder
J. Affect. Disord.
(1998)Atypical depression in private practice depressed outpatients: a 203-case study
Comp. Psychiatry.
(1999)Late-life atypical major depressive episode: a 358-case study in outpatients
Am. J. Geriatr. Psychiatry
(2000)- et al.
Sensitivity and specificity of DMS-IV atypical features for bipolar II disorder diagnosis
Psychiatry Res.
(2000) - et al.
Comparison of antidepressant drugs in depressive illness
Lancet
(1961) - et al.
Symptoms of interpersonal sensitivity in depression
Comp. Psychiatry
(1989) - et al.
Comparison of the diagnosis of melancholic and atypüical features according to DSM-IV and somatic syndrome according to ICD-10 in patients suffering from major depression
Eur. Psychatry
(1999) - et al.
The validity of atypical depression in DSM-IV
Comprehens. Psychiatry
(1996) - et al.
Biological and clinical validation of atypical depression
Psychiatry Res.
(1996)
Are neurovegetative symptoms stable in relapsing or recurrent atypical depressive episodes?
Biol. Psychiatry
The high prevalence of ‘soft’ bipolar (II) features in atypical depression
Comp. Psychiatry
Sleep of atypical depressives
J. Affect. Disord.
Pharmacotherapy response and diagnostic validity in atypical depression
J. Affect. Disord.
Atypical depression. A valid clinical entity?
Psychiatr. Clin. North Am.
Atypical depressive symptoms in seasonal and nonseasonal mood disorders
J. Affect. Disord.
The three-way interactions between the hypothalamic–pituary–adrenal and gonadal axes and the immune system
Ballière’s Clin. Rheumatol.
Social phobia, avoidant personality disorder and atypical depression: co-occurrence and clinical implications
Psychol. Med.
Recurrent brief psychiatric syndromes of depression, hypomania, neurasthenia, and anxiety from an epidemiological point of view
Neurol. Psychiatry Brain. Res.
Recurrent brief psychiatric syndromes: hypomania, depression, anxiety and neurasthenia
The Zurich Study—a prospective epidemiological study of depressive, neurotic and psychosomatic syndromes. I. Problem, methodology
Eur. Arch. Psychiatry Neurol. Sci.
Neurasthenia in young adults
Atypical depression: clinical aspects and noradrenergic function
Am. J. Psychiatry
Diagnostic and Statistical Manual of Mental Disorders
Diagnostic and Statistical Manual of Mental Disorders
Prevalence of bipolar II disorder in atypical depression
Eur. Arch. Psychiatry Clin. Neurosci.
The relationship between fatigue, psychological and immunological variables in acute infectious illness
Aust. NZ J. Psychiatry
Cerebral laterality and depression: Perceptual asymmetry in diagnostic subtypes before and after antidepressant treatment
J. Abnorm. Psychol.
The relationship between mortality and mental disorder: evidence from the Liverpool longitudinal study
Int. J. Ger. Psychiatr.
Atypical depression
Arch. Gen. Psychiatry
SCL-90. Administration, Scoring and Procedures Manual-I For the R (revised) Version and Other Instruments of the Psychopathology Rating Scales Series
Two-phase epidemiological surveys in psychiatry
Br. J. Psychiatry
DSM-III major depressive disorder in the community. A latent class analysis of data from the NIMH Epidemiologic Catchment Area Program
Br. J. Psychiatry
Latent class analysis of anxiety and depression
Sociol. Meth. Res.
The early course of atypical depression
Eur. Arch. Psychiatry Clin. Neurosci.
The Zurich Study XII. Sex differences in depression. Evidence from longitudinal epidemiological data
Eur Arch. Psychiatry Clin. Neurosci.
The chronic fatigue syndrome: a comprehensive approach to its definition and study
Ann. Intern. Med.
Low cerebrospinal fluid corticotropin-releasing hormone concentrations in eucortisolemic depression
Soc. Biol. Psychiatry
Isolation and characterization of a nuclear depressive syndrome
Psychol. Med.
The tyramine challenge test as a marker for melancholia
Arch. Gen. Psychiatry
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