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Traditionally, depressive disorders have been viewed as acute and time-limited. In recent decades, however, depression has been reconceptualized as a highly recurrent or chronic, and often lifelong, condition.1 Neither view is completely accurate.2 Rather, the course of depression is markedly heterogeneous and includes single brief episodes that remit and never recur, multiple acute episodes interspersed with periods of complete recovery, acute episodes followed by long periods of residual symptoms, and chronic episodes that may fluctuate in severity but persist for decades. This raises significant challenges for clinicians, patients, and family members trying to forecast the course of the disorder and formulate appropriate treatment plans, but it may also provide leverage in understanding the etiological and pathophysiological heterogeneity of depression.3

It has become increasingly evident that clinical diagnoses have only limited utility, in large part because ofthe heterogeneity that exists within each diagnostic category.4 As a result, the search for biomarkers and genes for specific diagnoses, such as major depressive disorder (MDD), has produced disappointing results,5,6 and the efficacy of pharmacological and psychosocial treatments has been limited.7 Most attempts to parse the heterogeneity of depression have focused on identifying distinctive patterns of symptoms (e.g., melancholia, atypical). However, these have had limited success.8 In part, this may be because patients’ reports of symptoms are often inconsistent over time when compared to more objective measures,9-11 and symptom-based subtypes tend to be unstable across episodes.12 In contrast, course-based indicators are based on information collected over lengthy periods of time. As a result, they may prove to have greater utility.

There are many important aspects of course, including age of onset, dura- tion/persistence of episodes, and recurrence and number of episodes.3 In this chapter, we focus on persistence, or chronicity, as a key aspect of course that may have some utility in parsing their heterogeneity. In addition, we limit our discussion to the large universe of nonpsychotic depressive conditions and do not consider psychotic and bipolar disorders.

Chronicity refers to episodes that persist for an extended period of time. Most investigators (and the third through fifth editions of the DSM13,14) require that episodes last at least 2 years to be considered chronic, although shorter (e.g., 1 year) and longer (5 years) periods have been used. Investigators also differ on whether full criteria for depression must be met for the entire time or whether periods of subthreshold symptomatology or brief remissions (e.g., up to 2 months) are permitted.

We begin with a brief review of naturalistic studies of the course of depressive disorders, discuss chronicity as a key subtyping feature for mood disorders, and then consider the role of chronicity in the problem of subthreshold depression.

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