Etiology

The etiology of the various subtypes of persistent depressive disorder, as well as other mood disorders, is unknown. It is likely that depressive disorders are heterogeneous in nature, and this may be particularly true for persistent depressive disorder, which has a wide range of presentations and varying severity.[24] One study reported an increased rate of chronic forms of depression in first-degree relatives of people with dysthymia, suggesting the possibility of a genetic or familial etiology in some cases.[25] However, a study of twin men did not reveal an increase in rates of dysthymia in monozygotic versus dizygotic twins.[26] One longitudinal study indicated that childhood inflammatory markers (IL-6) and lower intelligence (IQ) were predictors of subsequent depressive disorder symptoms.[27]

Chronic medical conditions may have associated depression, which may in some instances be in a persistent depressive disorder pattern. Acute and chronic stress may predict recurrence of depression following response to treatment.[28]

Pathophysiology

The pathophysiology of persistent depressive disorder is unknown. There has been discussion of whether dysthymia is an "Axis II" (personality) disorder rather than an "Axis I" (major mental) disorder as classified in the DSM-IV-TR manual (though the abolition of Axis II in DSM-5-TR has obviated this distinction).[29] However, treatment studies suggest that dysthymia is more akin to other Axis I mood disorders such as chronic major depression.[29][30][31] In addition to genetic contributions to the vulnerability for anxiety and depression, stressful early life events have been postulated to play a significant role in the pathogenesis of depression: early stressful life events may lead to hyperactivity of corticotropin releasing factor neurons and sensitization of the pituitary-adrenal stress response, and result in increased vulnerability to the effects of stress later in life.[32] Neuroimaging studies have shown numerous structural and functional brain changes in depression (major depression), and have found the subgenual cingulate cortex, hippocampus, amygdala and putamen as showing abnormalities.[33]

Alterations in serotonin and noradrenergic systems and dopamine have been demonstrated in various forms of chronic depression.

Classification

Diagnostic and statistical manual of mental disorders, fifth edition, text revision (DSM-5-TR)[1]

DSM-5-TR divides depressive disorders into:

  • Disruptive mood dysregulation disorder

  • Major depressive disorder (including major depressive episode)

  • Persistent depressive disorder

  • Premenstrual dysphoric disorder

  • Other specified depressive disorder

  • Depressive disorder due to another medical condition

  • Substance/medication-induced depressive disorder.

  • Unspecified depressive disorder.

Whereas in the DSM-IV and previous versions dysthymia was classified separately from other forms of chronic depression, such as chronic major depression, the DSM-5-TR has modified its classification system to include all chronic depressions under the single category of persistent depressive disorder, with the rationale that they are clinically similar in their response to treatment and their course of illness.[1]

Additional specifiers can be used to describe persistent depressive disorder:

  • With anxious distress: feelings of being keyed up or on edge, restlessness, difficulty concentrating because of worry, feelings that something awful may happen, and fears of loss of control.

  • With atypical features: mood reactivity; weight gain; increased sleep; heavy, leaden feelings in limbs; and sensitivity to interpersonal rejection that results in significant social or occupational impairment.

Severity may be classified as mild, moderate, or severe:

  • Mild: few, if any, symptoms in excess of those required to make the diagnosis are present, the intensity of the symptoms is distressing but manageable, and the symptoms result in minor impairment in social or occupational functioning.

  • Moderate: The number of symptoms, intensity of symptoms, and/or functional impairment are between those specified for "mild" and "severe."

  • Severe: The number of symptoms is substantially in excess of that required to make the diagnosis, the intensity of the symptoms is seriously distressing and unmanageable, and the symptoms markedly interfere with social and occupational functioning.

Age of onset is classified as early or late:

  • Early onset: onset before age 21 years

  • Late onset: onset after age 21 years

For the most recent 2 years of PPD, a specifier is added to describe any diagnosis of major depressive episode:

  • With pure dysthymic syndrome: full criteria for a major depressive episode have not been met in at least the preceding 2 years.

  • With persistent major depressive episode: full criteria for a major depressive episode have been met throughout the preceding 2-year period.

  • With intermittent major depressive episodes, with current episode: full criteria for a major depressive episode are currently met, but there have been periods of at least 8 weeks in at least the preceding 2 years with symptoms below the threshold for a full major depressive episode.

  • With intermittent major depressive episodes, without current episode: full criteria for a major depressive episode are not currently met, but there has been one or more major depressive episodes in at least the preceding 2 years.

International classification of diseases, eleventh revision (ICD-11)[3]

In contrast to DSM-5-TR, in the ICD-11 classification, individuals who present with symptoms of chronic depression without meeting criteria for major depressive disorder within the first 2 years would be classified as having dysthymic disorder. Similar to the DSM-5-TR, depressive symptoms must be present more days than not. After the first 2 years, other depressive diagnoses can be assigned to individuals with dysthymic disorder, such as single episode, depressive disorder, or recurrent depressive disorder. The DSM-5-TR has given priority to chronicity over symptom severity in combining several categories into the diagnosis of persistent depressive disorder.[2] In contrast, the ICD-11 work group reportedly felt that there was insufficient evidence for concluding that chronic major depression and dysthymic disorder were the same condition, and hence retained the separate dysthymic disorder diagnosis. 

Also of note, the ICD-11 and DSM-5-TR criteria for major depressive disorder, while largely similar, differ in that the ICD-11 includes "feeling hopeless" as a separate symptoms, of which 5 out of 10 criteria must be met for an ICD-11 diagnosis of major depressive episode, compared to 5 out of 9 symptoms in the DSM-5-TR. The ICD-11 addition of hopelessness to major depression diagnostic criteria resulted from empirical evidence that it more powerfully distinguished depressed from nondepressed individuals.[2] This may be relevant to many individuals with persistent depressive disorder, particularly those with current major depressive episodes.

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