Chronic Depression: Diagnosis and Classification

Current Directions in Psychological Science 19(2) 96-100 ª The Author(s) 2010 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0963721410366007 http://cdps.sagepub.com

Daniel N. Klein Stony Brook University

Abstract Traditionally, non-bipolar depression has been viewed as an episodic, remitting condition. However, with the recognition that depressions can persist for many years, the current diagnostic classification system includes various forms of chronic depression. The distinction between chronic and nonchronic depressions is useful for reducing the heterogeneity of the disorder. Individuals with chronic depression differ from those with nonchronic depression on a variety of clinically and etiologically significant variables, including comorbidity, impairment, suicidality, history of childhood maltreatment, familial psychopathology, and long-term course. In contrast, there is little support for current distinctions between different forms of chronic depression. This suggests that it may be simpler to collapse the existing forms of chronic depression in the current classification system into a single category. However, there is growing evidence that other characteristics, such as age of onset and a childhood history of early adversity, may provide meaningful approaches to subtyping chronic depression. Keywords depression, chronic, mood disorders, dysthymic disorder, double depression

Traditionally, depressive disorders have been conceptualized as episodic, remitting conditions. However, following the publication of several seminal papers in the late 1970s and 1980s (Akiskal et al., 1980; Keller & Shapiro, 1982; Kocsis & Frances, 1987; Weissman & Klerman, 1977), it is now widely recognized that many individuals suffer from chronic conditions that can last for decades. Chronic depression is significant for several reasons. It is a common problem from a public health perspective: The lifetime prevalence of chronic depression is approximately 3% to 6% in community and primary care samples (e.g., Satyanarayana, Enns, Cox, & Sareen, 2009); and more than a third of patients may suffer from chronic depression in general outpatient mental health settings (see Klein, 2008b). Chronic depression is also associated with considerable functional impairment, often greater than in nonchronic major depression (e.g., Gilmer et al., 2005; Satyanarayana et al., 2009), and it may also be associated with greater suicidality and more hospitalizations (Klein, Shankman, & Rose, 2006). From a research perspective, non-bipolar, nonpsychotic depressive disorders are a highly heterogeneous group of conditions, complicating the search for causes and the development of efficacious interventions. However, as I will discuss, there is evidence that whether or not it is chronic (i.e., chronicity) may be useful in parsing the heterogeneity of non-bipolar depression. In this

article, I provide a brief overview of research on the diagnosis and classification of chronic depression.

Chronic Depression in the DSM-IV In an attempt to cover the broad variety of trajectories that the mood disorders can take, the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV; American Psychiatric Association, 1994) includes a number of categories, subtypes, and specifiers relevant to chronic depression (see Fig. 1). Dysthymic disorder is defined as a mild condition (depressed mood plus at least two other depressive symptoms) that is chronic (depressed most of the day, more days than not, for at least 2 years) and persistent (no symptom-free periods of longer than 2 months) and has an insidious onset (no major depressive episode within the first 2 years of the disturbance). It can present with the full gamut of depressive symptoms, although cognitive symptoms (e.g., low self-esteem, hopelessness), affective symptoms (dysphoric mood), and social-motivational Corresponding Author: Daniel N. Klein, Department of Psychology, Stony Brook University, Stony Brook, NY 11794-2500 E-mail: [email protected]

Chronic Depression

Fig. 1. Pictorial representation of various course configurations of non-bipolar depression. The horizontal axis represents time and the vertical axis represents mood, with the horizontal black line representing euthymic, or normal, mood, and the magnitude of downward deflection (the blue area) reflecting severity of depressive symptoms. Panel (a) is non-chronic major depressive disorder (in this case, recurrent, as two depressive episodes are depicted). Panel (b) is dysthymic disorder. Panel (c) is double depression (major depressive episode superimposed on antecedent dysthymic disorder). Panel (d) is chronic major depressive episode. Panel (e) is major depressive episode in partial remission. Panel (f) is recurrent major depression without full interepisode recovery.

symptoms (e.g., social withdrawal) are more common than vegetative symptoms (e.g., sleep and appetite disturbance). Although dysthymic disorder may be relatively mild at any given point, the cumulative burden of persistent depressive symptoms and impaired functioning is substantial and can be greater than that of more severe acute depressions (e.g., Holm-Denoma, Berlim, Fleck, & Joiner, 2006). Most persons with dysthymic disorder experience exacerbations that meet criteria for a major depressive episode (Klein et al., 2006). Indeed, this is often what leads individuals with dysthymic disorder to seek treatment. Though it is not a formal category in the current classification system, the superimposition of a major depressive episode on antecedent dysthymia is referred to as ‘‘double depression.’’ In DSM-IV, such patients receive diagnoses of both major depressive disorder and dysthymic disorder. Although this implies that these are two distinct, comorbid conditions, it is likely that the dysthymia and major depressive episodes in patients with double depression represent different phases of a single condition that waxes and wanes, often in response to stressful life events (Klein, 2008b). Major depressive episode, chronic type, refers to a more severe condition that meets full criteria for major depression (defined by depressed mood or loss of interest most of the day, almost every day) continuously for a minimum of 2 years. It differs from dysthymic disorder in that more symptoms are required (a minimum of five) and it is somewhat more persistent (‘‘nearly every day’’ instead of ‘‘more days than not’’). Approximately 20% of patients with a major depressive episode meet criteria for the chronic specifier (Gilmer et al., 2005).

97 The DSM-IV includes several additional episode and course specifiers relevant to chronic depression. In coding the severity of major depressive episodes, DSM-IV includes an option for patients who are in partial remission. This refers to patients who have recovered to the point they no longer meet full criteria for a major depressive episode but continue to experience significant symptoms. The distinction between full and partial remission is important because the persistence of subthreshold symptoms is associated with significant functional impairment and an increased risk of recurrence (Judd et al., 2000). In many cases, these subthreshold depressive symptoms can persist for many years. Such cases can be considered another form of chronic depression. If these patients experience a recurrence, they qualify for the DSM-IV longitudinal course specifier, ‘‘recurrent major depression without full interepisode recovery.’’ If the total continuous duration of illness is greater than 2 years, this can also be viewed as a form of chronic depression.

Distinction Between Chronic and Nonchronic Depression In the 1980s and early 1990s, there was vigorous debate over whether chronic depressions (particularly dysthymic disorder) are better conceptualized as personality disorders than as mood disorders, due to their chronic course and often early onset. This controversy eventually subsided following evidence that most individuals with dysthymic disorder develop major depressive episodes at some point, dysthymic disorder and major depressive disorder occur in the same families, and both dysthymic disorder and double depression respond to antidepressant medications (Klein, 2008b). However, the evidence for a close relationship between dysthymic disorder and major depressive disorder then raises the question of whether existing classificatory distinctions between these two conditions, or between chronic and nonchronic depressions more generally, are meaningful and useful. If not, it would be simpler and more efficient to classify depression as a unitary diagnostic construct. A number of studies have reported that dysthymic disorder and double depression differ in important ways from nonchronic major depression. Fewer studies have compared chronic and nonchronic major depressive disorder, but the results have generally been similar. Thus, persons with chronic depression have an earlier onset (Angst, Gamma, Ro¨ssler, Ajdacic, & Klein, 2009; Klein, Shankman, Lewinsohn, Rohde, & Seeley, 2004; Mondimore et al., 2006); higher rates of comorbid Axis I (e.g., anxiety disorders) and Axis II (personality disorders) conditions (e.g., Angst et al., 2009; Gilmer et al., 2005; Holm-Denoma et al., 2006; Mondimore et al., 2006); more extreme personality traits, such as neuroticism, and higher levels of at least some depressive cognitive biases (e.g., Riso et al., 2003); and greater suicidality (Gilmer et al., 2005; Holm-Denoma et al., 2006; Klein et al., 2006; Mondimore et al., 2006) than do persons with nonchronic major depression. Individuals with chronic depression also report having experienced greater childhood adversity and maladaptive

98 parenting than do persons with nonchronic major depression (e.g., Brown, Craig, & Harris, 2008). Indeed, childhood adversity is one of the strongest predictors of chronicity and is correlated with duration of depression even within samples of chronically depressed individuals (Klein et al., 2009). In addition, the relatives of persons with chronic depression exhibit higher rates of depressive disorders than do the relatives of persons with nonchronic major depression (Klein et al., 2004), and chronic depression in mothers has a greater impact on infants than nonchronic major depression does (Field, Diego, Hernandez-Reif, & Ascencio, 2009). Not surprisingly, a history of chronic depression predicts a more chronic course of the current depressive episode and poorer subsequent outcomes (Klein et al., 2006; Rhebergen et al., 2009). Finally, although direct comparisons are rare, chronic depressions appear to require somewhat different approaches to treatment than nonchronic depressions do. Treatment response rates tend to be lower in chronic than in nonchronic depressions, and chronic depressions appear to require a longer duration of pharmacotherapy and may be more likely to benefit from combined pharmacotherapy and psychotherapy than does nonchronic major depression (Keller et al., 2000). Thus, chronic depressions appear to be associated with higher levels of many risk factors and greater impairment than are nonchronic depressions. On the face of it, this may not be surprising, but in fact the prototypical form of chronic depression—dysthymic disorder—has traditionally been conceptualized, and indeed is defined, as being less severe than acute depressions. More importantly, these differences raise the possibility that chronicity may provide leverage in dividing the heterogeneous group of non-bipolar depressions into somewhat more homogeneous subgroups. The hypothesis that the chronic/nonchronic distinction may reflect stable underlying differences in causes and development is supported by two further sets of findings. First, the distinction between chronic and nonchronic depression is stable over time. In their 10-year follow-up, Klein et al. (2006) found that patients with dysthymic disorder and double depression were 14 times more likely to exhibit a chronic course than were patients with nonchronic major depression, whereas patients with nonchronic major depression were 12 times more likely to exhibit a nonchronic depressive course. Second, chronic depression runs in families. That is, relatives of individuals with chronic depression have significantly higher rates of chronic depression than do relatives of patients with nonchronic major depression (e.g., Mondimore et al., 2006).

Distinction Between Forms of DSM-IV Chronic Depression Thus, there appear to be a number of clinically and potentially etiologically significant differences between chronic and nonchronic forms of depression. Do the various categories, subtypes, and specifiers for chronic depression in the DSM-IV also capture clinically and etiologically significant variability?

Klein Only a handful of studies have compared different forms of chronic depression. Several studies compared dysthymic disorder and double depression; several compared dysthymia and chronic major depression; and several compared double depression, chronic major depression, and, in one study, recurrent major depression with incomplete recovery between episodes and a continuous duration of at least 2 years. In all of these studies, there were virtually no differences between the different forms of chronic depression in terms of comorbidity, personality, functional impairment, depressive cognitions, coping style, childhood adversity, familial psychopathology, response to pharmacotherapy and psychotherapy, and naturalistic course and outcome (see Klein, 2008b, for a review). The lack of distinctiveness between the various forms of chronic depression is also supported by within-subject longitudinal data. As noted above, almost all patients with dysthymic disorder experience exacerbations that meet criteria for major depressive episodes, suggesting that dysthymic disorder and double depression are different phases of the same condition. In addition, in our 10-year follow-up study, we found that although patients with dysthymic disorder and double depression often experienced recurrences of chronic depression, the form of chronic depression varied. Of the patients who experienced a recurrence of chronic depression, 28% met criteria for dysthymic disorder, 24% met criteria for a chronic major depressive episode, and 48% had a period of chronic depression that did not meet criteria for either category (e.g., major depression with partial remission and a continuous duration of over 2 years; Klein et al., 2006). Thus, there is little evidence that the existing DSM-IV distinctions between the various forms of chronic depression are stable, etiologically meaningful, or clinically useful. On the other hand, as discussed above, there do appear to be important differences between chronic and nonchronic forms of depression. This suggests that in the interest of parsimony, the various forms of chronic depression recognized in the DSM-IV can be combined into a single group of chronic depressions and contrasted with nonchronic depression. Elsewhere we have argued that with the addition of an axis or dimension for severity, a simple two-axis or two-dimension scheme of chronicity by severity can account for most of the categories, subtypes, and specifiers included in the DSM-IV classification of depressive disorders (Klein, 2008a).

Chronic Depression Subtypes Although the distinction between chronic and nonchronic depression may reduce the heterogeneity of the large group of non-bipolar, nonpsychotic depressions, chronic depression is still probably heterogeneous, even if this heterogeneity is not adequately captured in the DSM-IV. Based on Akiskal’s seminal work (e.g., Akiskal et al., 1980), the DSM includes early-onset (< age 21) and late-onset ( age 21) subtypes for dysthymic disorder. Although it is unclear whether age 21 is the optimal cutoff point (or indeed whether age of onset is better conceptualized dimensionally), there is considerable support

Chronic Depression

99 these subtypes: familial loading of depression (in the subaffective subtype) and childhood maltreatment and adversity (in the character-spectrum subtype). Dougherty, Klein, and Davila (2004) examined moderators of the influence of chronic stress on the maintenance of depressive symptoms in chronic depression. They found that patients with a high familial loading for chronic depression were unaffected by chronic stress, whereas chronic stressors were closely associated with subsequent changes in depressive symptoms among patients with a history of early adversity (Fig. 2). In a large multisite trial for chronic depression, Nemeroff et al. (2003) reported that patients who had a history of early adversity were significantly more likely to achieve remission with cognitive-behavioral psyschotherapy than with pharmacotherapy, whereas patients without early adversity exhibited a trend for higher remission rates with pharmacotherapy than with psychotherapy. More recently, in another large multisite trial, Klein et al. (2009) also found that early adversity predicted a significantly poorer response to antidepressant medication. Taken together, these data suggest that there may be several distinct developmental pathways in chronic depression, at least one of which is characterized by a strong familial liability and is responsive to pharmacotherapy, and another that is characterized by early adversity and is more responsive to psychosocial interventions.

Fig. 2. Depression severity (measured by Hamilton Depression Rating Scale, HAM-D) as a function of chronic stress for those with better versus adverse parent–child relationships (top graph) and for those with family history (high familial loading) versus no family history (low familial loading) of dysthymic disorder (bottom graph).

for such a distinction. Early-onset dysthymic disorder is associated with increased comorbidity with Axis I and II disorders, greater childhood adversity, a stronger family history of mood disorders, and greater neuroendocrine dysregulation than is late-onset dysthymic disorder (see Klein, 2008b, for a review). In contrast, late-onset dysthymic disorder may be more closely associated with stressful life events, particularly chronic stressors related to general medical disorders or the illness or loss of loved ones. These data suggest that early- and late-onset dysthymic disorder may reflect at least two different etiological pathways. Although DSM-IV limits the early-/late-onset distinction to dysthymia, the pattern of differences between patients with early- and late-onset chronic major depressive disorder are very similar, suggesting that age of onset is an important source of heterogeneity in the broader group of chronic depressions, and perhaps in the mood disorders more generally (Klein, 2008b). Akiskal et al. (1980) also suggested that early-onset chronic depressions could be further divided into subaffective and character spectrum subtypes, regarding the former as a mild, chronic type of severe depression and the latter as reflecting a personality disorder. Although support for this distinction has been limited, there is emerging evidence for the importance of several of the features highlighted by Akiskal in discussing

Recommended Reading Gilmer, W.S., Trivedi, M.H., Rush, A.J., Wisniewski, S.R., Luther, J., Howland, R.H., et al. (2005). (See References). The most comprehensive study in the small literature comparing chronic and nonchronic major depressive disorder. Klein, D.N. (2008a). (See References). A paper proposing an alternative approach to classifying depressive disorders, drawing on some of the work discussed in this article. Klein, D.N. (2008b). (See References). Provides a broader and more detailed review of the literature on chronic depression. Klein, D.N., Shankman, S.A., & Rose, S. (2006). (See References). Reports the main findings from the longest prospective followup study of chronic depression published to date. Mondimore, F.M., Zandi, P.P., MacKinnon, D.F., McInnis, M.G., Miller, E.B., Crowe, R., et al (2006). (See References). A paper, from a large collaborative study on the genetics of recurrent depression, demonstrating that chronic depression runs in families.

Declaration of Conflicting Interests The authors declared that they had no conflicts of interest with respect to their authorship or the publication of this article.

Funding Preparation of this article was supported in part by National Institute of Mental Health Grant R01 MH069942.

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