Research report
Toward validation of atypical depression in the community: results of the Zurich cohort study

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Abstract

Aims: This paper (1) examines the validity of the atypical subtype of depression in a community-based longitudinal cohort study, (2) presents estimates of the prevalence and sex differences of DSM-IV atypical depression and a newly more broadly defined atypical syndrome in the community and (3) compares the clinical correlates and treatment patterns of those with atypical depression with other depressives. Methods: The Zurich cohort study is comprised of 591 subjects selected from a population-based cohort of young adults representative of the canton of Zurich in Switzerland, who were screened in 1978 with the Symptom Checklist 90-R [L.R. Derogatis (1977)] and followed prospectively with five interviews between 1979 and 1993. Atypical depression was defined on a spectrum ranging from atypical major to minor to atypical depressive symptoms alone. Results: The rate of DSM-IV atypical major depressive episodes in this community is 4.8% and for major atypical depression syndrome is 7.3%. Whereas there was no marked sex difference for nonatypical features, there was a significant female preponderance for DSM-IV and broadly defined atypical depressive subtypes. Systematic investigation of the diagnostic criteria for atypical depression revealed that a nonhierarchical definition of atypical depression with respect to mood reactivity yielded as valid a syndromic definition as the current hierarchy based on mood reactivity as an essential feature. Very high comorbidity (odd ratios>2.0) was found with seasonality, bipolar II, social phobia, binge eating, neurasthenia and sociopathy. Limitations: Atypical depression was not defined à priori, its criteria were derived from two sections of the Zurich interview. Conclusions: Atypical depression has high population prevalence and substantial significance in terms of clinical severity, impairment, and service use. The intriguing finding that the sex difference in depression may be attributed to atypical features of depression will need further investigation. Overall, our data indicate that the atypical subtype of depression is a valid entity based on evidence from such traditional indicators of validity as inclusion criteria and indicators of course. However, there are some problems with discriminatory validity from other disorders. Although comorbidity with these disorders may in part reflect an operational artifact of symptom overlap, further work needs to be done in distinguishing atypical depression from bipolar II.

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.

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