Dysthymia: historical/nosological characteristics and its relationship with major depressive disorder

Abstracts

Transtorno distímico é uma forma crônica e incapacitante de depressão, ocorrendo em uma parcela substancial da população (3 a 6%) e aumentando os riscos de transtorno depressivo maior. Ela é associada a consideráveis incapacitações e elevada comorbidade. O status nosológico da distimia tem despertado consideráveis controvérsias ao longo das décadas passadas, sendo que algumas investigações a consideraram como um transtorno do humor e outras como um transtorno de personalidade. Classificada na nosografia atual entre os transtornos de humor, a distimia é hoje uma entidade tratável e que precisa receber maior atenção em virtude de sua morbidade. Este artigo revisa os principais aspectos históricos da distimia, suas características nosológicas, subtipos e sua relação com transtorno depressivo maior. Ao final, concluímos que novos estudos são necessários para a validação do conceito de distimia e do espectro de depressões crônicas, para uma melhor compreensão etiológica e para uma terapêutica baseada em evidências.

Distimia; depressão; transtornos do humor; comorbidade; aspectos históricos e nosológicos

REVIEW ARTICLE

Dysthymia: historical/nosological characteristics and its relationship with major depressive disorder

Distimia: características históricas y nosológicas y su relación con el trastorno depresivo mayor

Lucas Spanemberg^I; Mario Francisco Juruena^II

^IMedical student, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (FFFCMPA), Brazil

^IIPsychiatrist; Honorary Lecture of Academic Department of Psychological Medicine, King's College School of Medicine & Institute of Psychiatry - University of London; Clinical Research Fellow South London Maudsley Trust

^{Correspondence}

ABSTRACT

Dysthymia is a chronic and incapacitating form of depression that affects a substantial portion of the population (3-6%) and increases the risk for major depressive disorder. It is associated with significant disabilities and high comorbidity. The nosological status of dysthymia has been associated with considerable controversy over the past decades: some investigators regard it as a mood disorder, and others as a personality disorder. Currently classified among the mood disorders, dysthymia is now a treatable disorder and should receive more attention in view of its associated morbidity. The present article reviews the main historic aspects of dysthymia, its nosological features and its relationship with major depressive disorder. We conclude that further studies are necessary in order to validate the concept of dysthymia and the spectrum of chronic diseases, in order to provide a better understanding of the disorder as well as evidence-based guidelines.

Keywords: Dysthymia, depression, mood disorders, comorbidity, historical and nosological aspects.

RESUMEN

El trastorno distímico es una forma crónica e incapacitante de depresión, que ocurre en una parcela significativa de la población (3 a 6%) y aumenta los riesgos de trastorno depresivo mayor. Está asociada a incapacitaciones considerables y elevada comorbilidad. El status nosológico de la distimia viene provocando muchas controversias a lo largo de las décadas pasadas, siendo que algunas investigaciones la consideraron como siendo un trastorno del humor y otras como un trastorno de personalidad. La nosografía actual la clasifica entre los trastornos del humor, siendo hoy una entidad tratable y que necesita de más atención a causa de su morbilidad. Este artículo revisa los principales aspectos históricos de la distimia, sus características nosológicas, subtipos y su relación con el trastorno depresivo mayor. Al final, concluimos que se necesita de nuevos estudios para validar el concepto de distimia y el espectro de depresiones crónicas, para una mejor comprensión etiológica y para una terapéutica con base en evidencias.

Palabras clave: Distimia, depresión, trastornos del ánimo, comorbilidad, aspectos históricos y nosológicos.

INTRODUCTION

Dysthymia is a form of non-episodic chronic depression, with less intense symptomology than seen with the disorders known as major depressions.^1-4 The basic pattern with these patients is of low-level symptoms, which develop insidiously, in the majority of cases before they are 25.⁵ Despite the symptoms being milder, the fact that the disease is chronic and that it is not recognized means that the prejudice to patient quality of life is considered greater than with other types of depression.⁶

Patients with dysthymic disorder are often sarcastic, nihilistic, morose, demanding and plaintive. They may be tense, rigid and resistant to therapeutic interventions, although they attend sessions regularly. As a result, the doctor may become irritated with the patient and even disregard their complaints.⁷ Although the disorder progresses with relatively stable social function, this stability is relative, since many of these patients invest the energy they do have in their work and nothing is left over for pleasure and family and social activities, which results in characteristic marital friction.⁸

In terms of evolution, dysthymia may be an adaptive subtype of mood which has developed in order to cope with states of stress or need.⁹ Thereby certain types of depressive mood might have offered evolutionary advantage under specific conditions (in which the lack of action and initiative would be more appropriate for avoiding risk to life),¹⁰ and, being beneficial within certain subpopulations and environments, are selected over time. As a maladaptive condition, dysthymia manifests clinically as withdrawal from the routine of daily activities instead of facing them. Differences in sex^11,12 — female predominance — in dysthymia and depression may also have evolutionary causes.^9,13

The prevalence of dysthymia is approximately 3 to 6% of the general population,^4-6,14,15 and is one of the most common conditions found in medical practice.⁵ These patients do not seek help^2,3,6 or suffer their symptoms for long periods and generally consult clinical doctors with ill-defined complaints such as general unwellness, lethargy and fatigue.^5,16 Around 50% of these patients will not be recognized by clinicians,^1,2,17 and a majority will exhibit a series of comorbidities.^3,5,14 In common with major depressive disorder (MDD), dysthymia is twice as common among women than among men,^1,6,11-13 and is also more common among single people.^18-20 When married, these people have unsatisfactory relationships. They are also prone to multiple complaints and unsatisfied with life.¹⁶

The etiology of dysthymia is both complex and multifactorial, with etiologic biological and psychological mechanisms involved. These multiple factors — heredity, predisposition, temperament, lifestyle factors, biological stressors, gender, etc. — converge to produce dysregulation of the system of balances.⁸ Stress causing events during childhood^20-23 are very frequent.

Since dysthymia is associated with an increase in health service utilization and also an increase in psychotropic drug usage, enormous financial costs can be attributed to this disorder.^14,17,24 Reduced productivity at work and an increased risk of hospital admission^14,19 and physical diseases (including increased risk of cardiovascular and respiratory diseases)¹⁴ also increase the social and economic cost of this pathology, making it a public health problem that needs to be identified more efficiently. The high rate of comorbidity with other psychiatric disorders (around 77% of dysthymics will have psychiatric comorbities)²⁵ make the diagnosis of dysthymia even more important so that comorbid psychopathologies can be adequately managed.

This article aims to review the principle historical and nosological aspects of this disorder and also its relationship with MDD. The subtypes of the disorder will be discussed as will the controversies of categorical versus dimensional distinctions of dysthymia and of its relationship to other mood disorders. In order to accomplish this a selection was made, by convenience, of the most pertinent articles in the LILACS and MEDLINE databases. The article will finish by discussing the current state of the theme and its importance to current psychiatry. The terms "dysthymic disorder" and "dysthymia" will be used as synonyms, since both are used a lot in current research.

HISTORICAL CHARACTERISTICS

The term "dysthymia" originated in Ancient Greece and means "bad temper".^1,26 In the Greek Hippocratic school it was considered a part of the concept of melancholy, a term derived from the temperament or character characteristic of the influence of, or intoxication by "black bile", one of the four "primary humors".^1,27,28 Thus, individuals who were lethargic, worried and insecure were predisposed to a melancholic temperament.¹ Claudius Galen of Pergamon (128-201 A.D.) described melancholics as introspective, pessimistic and with lean bodies²⁷ — "if fear of depression lasts a long time, this state is proper to melancholy", Galen said.²⁹ He established melancholy as being a chronic and recurrent condition, which could be a primary disease of the brain or secondary to other diseases.³⁰ Soranus of Ephesus described melancholic patients as having prejudicial symptoms of paranoia and depression.²⁷

From Ancient Greece to the Middle Ages, mental disease was dealt with by clerics and religious persons, once it had come to be attributed to magic, to sin and to demonic possession, the target of the Holy Inquisition.³⁰ During the same period, the Arab world was making important re-readings of the concept of melancholy, with Avicenna (980-1037), Maimonides (1135), Averrois (1126) and Constantine (1019-1087), among others.²⁷

During the Renaissance, Robert Burton published his Anatomia of Melancholy (1621). In this work, Burton lists, among other causes of melancholy, advanced age, temperament and heredity, and also establishes it as a secondary cause of bodily diseases.²⁷ In the eighteenth century, William Cullen (1710-1790), under the influence of the enlightenment, associated melancholy with a primary instability of the brain and suggested "restrictions" as the best remedy to reduce excitement.²⁷

The nineteenth century brought an increasing interest in the minor forms of mood disorders (folie circulare "circular insanity"), which, according to Falret (1824-1902), a trained observer could see as part of a continuum with major disease.²⁸ Falret wrote about attenuated forms of the circular disease and, later, in 1863, Karl Ludwig Kahlbaum used the terms "cyclothymia", for the milder forms of mood fluctuation, and "dysthymia" for forms of the disease (melancholy) that exhibit just one phase of attenuated depression.^26,28 This description, from Germany in the nineteenth century, appears to have been the first approach to using the term in the sense of mild chronic depression, and not as a depressive psychopathic temperament.²⁸

The term "depression" began to appear in medical dictionaries in 1860, being widely accepted and the term "melancholy" was restricted more and more.²⁷ Esquirol (1772-1840) suggested that the word "melancholy" be reserved for the use of poets. Berrius, student of the history of psychiatry, indicated that the term "depression" supplanted the thousand-year-old "melancholy" as a result of the apparent physiological and metaphorical impression of the fall in function that it suggests.²⁷

In 1921, Emil Kraepelin described the relationship between the depressive temperament and maniac-depressive insanity, suggesting that the former was an attenuated form, but belonged to the same pathological constellation as the full disease,^18,26,28 in a continuum model.^5,7 The characteristics of the depressive temperament would be the constant, although fluctuating, presence of sadness, anxiety, pessimism and lack of pleasure.²⁸ Kraepelin defended a classification of mental disease founded on patients' natural histories and the evolutionary course of their disorders before their psychiatric symptoms.²⁶ He thereby developed the concept of nosological status and grouped affective disorders under the aegis of maniac-depressive insanity, separating these from premature dementia (schizophrenia).^7,27 This dichotomous proposal is still the strongest taxonomy concept in current psychiatry.²⁷

In 1923, Kurt Schneider, described dysthymic or depressive psychopathy in his monograph,²⁶ related to an etiologic combination of hereditary and neonatal factors and to early environmental variables — and not to a mood disease (depressive).¹⁸ Using the term "personality", Schneider defined certain constitutional variations of the normal as abnormal personalities, thereby considering depressive psychopathy within the field of personality disorders.³¹

In 1936, Kretschmer reinforced the idea of a continuum from the basic temperament to the disease, raising it to the height of its importance. He only opposed Kraepelin's concept of nosological unity and introduced what is known as dimensional diagnosis, in opposition to the categorical diagnosis of Kraepelin.²⁷

Under the influence of the psychoanalytic and Schneiderian concepts, the official American classification (Diagnostic and Statistical Manual of Mental Disorders - DSM-II, 1968) and the Global system (International Classification of Diseases - ICD-9, 1978), the idea that chronic depression is equivalent to the character neuroses was disseminated, disconnecting it from the affective disorders and linking them to personality disorders.¹⁸ Thus, during the 60s and 70s, the DSM-II included "Neurotic Depression", and ICD-9, "Depressive Neuroses", but both included non-chronic episodes.²⁶ Overall, the view that personality disorders were untreatable would represent an insurmountable conceptual problem, being made even more complex by the fact that normal personalities exist that have varying traces of abnormality and that do not necessarily represent psychiatric disorders.²⁶

Indeed, in 1978 Akiskal et al. published a 3 to 4 year follow-up study of 100 depressive neurotics and did not find any clinical significance to the diagnosis of neurotic depression. Monitoring the patients found evidence of the widest variety of nosological diagnoses, both of other mood disorder modalities and other pathologies entirely.^18,26,27 The variety of nosological diagnoses that Akiskal et al. found led them to conclude that the diagnosis of neurotic depression did not possess sufficient phenomenological properties of its own to constitute a distinct nosological entity.¹⁸ This represented significant support for the establishment of the empirical basis of dysthymia in its current sense²⁶ and was a milestone in the nosological history of mood disorders.

Under the influence of new discoveries, the DSM-III changed the reference to chronic depression to "Dysthymic Disorder" substituting the previous DSM-II definition, "Neurotic Depression" and is included in the affective disorder chapter. Despite the descriptive model called "atheoretical" with respect of etiology (operationalized), this position marks the removal of chronic depressions from the domain of character and personality disorders. Despite this evolution, dysthymic disorders still included a wide variety of entities, with primary depressions with residual chronicity, secondary chronic dysphoria and character-based depressions (personality disorders and dysthymic disorder itself).¹⁸ The DSM-III-R and the DSM-IV incorporated some of these definitions,²⁶ and, in the appendix to DSM-IV, the depressive personality disorder had already appeared.^1,32,33

The ICD-10 is not yet able to establish a concept of dysthymia that is essentially different from depressive neurosis or neurotic depression,²⁶ in other words, this is a wider concept than that of the DSM-IV. The differences between the diagnostic criteria of the two manuals reflect the fact that the DSM-IV is also aimed towards research, while the ICD-10 is designed solely for clinical application. Furthermore, the policy composition of the ICD-10 is greatly more complex as it aims to include the entire world and not just one country.^32,34 Both, despite their differences, consider that dysthymia is a chronic unipolar affective disorder (lasting at least 2 years), with early or late onset, and symptomology that is less intense than is observed in a depressive episode and symptoms including insomnia, lack of energy and fatigability, low self-esteem, reduced capacity to concentrate and loss of interest and pleasure.³⁴

Nowadays, just as Kraepelin described 100 years ago, it is accepted that dysthymia is an attenuated variant of the affective disorder spectrum. In modern terminology, dysthymia can be considered as a less severe form of depression which increases the risk of major depression.³ The principle characteristics are chronic, low-intensity symptoms (for at least 2 years), an insidious, early onset and persistence.⁸

NOSOLOGICAL ASPECTS

The current official nosology classifies dysthymia as a mood disorder, differentiated from MDD by being chronic and les severe.^3,4,8

The profile of dysthymic disorder reveals a tendency to a predominance of symptoms over signals (depression is more subjective than objective); another difference in relation to MDD.^2,7 Serretti et al.,⁴ in a study of 512 dysthymic patients without MDD, found that cognitive and emotional symptoms were more characteristic than vegetative and psychomotor symptoms. Low self-esteem, anhedonia, fatigue, irritability and low concentration are present in more than half of the patients.⁴ Accordingly they did not highlight accentuated distortions in appetite and libido, neither did they observe agitation or psychomotor retardation.² Since those patients that frequently seek treatment fluctuate, going in and out of major depressive episodes, the essence of the DSM-IV criteria for dysthymic disorder tend to emphasize the vegetative dysfunction, while the alternative criterion B for dysthymic disorder, in the appendix to DSM-IV, lists cognitive symptoms.⁸ This alternative classification for dysthymia aims to stimulate a greater characterization of the disorder with respect of other mood disorders.¹⁴

The essential standards of dysthymic disorder habitually include sadness, lack of joie de vivre and concern with inadequacy. The disorder is best considered as a low-intensity depression that fluctuates and is lasting, experienced as part of the normal "self" and representing an intensification of the traces observed in depressive temperaments (subthreshold form).^2,8 Dysthymic disorder may, therefore be seen as a more symptomatic (or threshold) form of this temperament (depressive personality disorder).⁸ This gives weight to the model of a severity spectrum for depression, in which the different forms of depression exist along a continuum from the subsyndromal forms to the full-blown disease.²⁵ Akiskal is the contemporary author who has most studied the hypothesis of a dimensional relation between personality and mood disorders.^25-35 This model, originally conceptualized by Kraepelin, suggests that the subthreshold depressive symptoms, may in fact represent the most common expressions of depressive disorders.⁸

Some authors have offered significant contributions on the subject. Angst & Merikangas,³⁶ performed a 15-year longitudinal follow-up study of 591 individuals, investigating the application of diagnostic criteria to threshold and subthreshold depression categories (MDD and dysthymia). Their main conclusions, at the end of their observations, reinforced the idea of a depressive spectrum. The prevalence rates of threshold and subthreshold depression categories were similar with approximately 17% of the general population combining the criteria for one or another depressive category during the period. Few individuals with depression fulfilled criteria for just one depressive subtype after 15 years — i.e. there were very few "pure" subtypes. Subthreshold depression types were associated with a large increase in the risk of subsequently developing MDD (a strong predictor of depression), with approximately half of the subjects eventually developing major depression. Major depressive disorder was also associated with an increased risk of developing subthreshold depression, with half of those individuals who had MDD also fulfilling criteria for subthreshold categories of depression during the follow-up period. During follow-up dysthymics had a higher rate of hospital admissions (11% versus 7%) and were more often treated for depression (77.8% versus 54.7%) than were patients with MDD episodes. Patients with recurrent short-term depression also had a greater rate of treatment (60.6%) than did patients suffering episodes of MDD.³⁶

It was Angst who introduced the term "threshold psychiatry", which refers to the psychiatric classification categories used in diagnostic manuals, such as the DSM-IV, and which, according to him, do not take sufficient account of the depressive dimension. With a basis in epidemiological studies, Angst claims that some of the disorders that do not unite contemporary diagnostic criteria have subjective levels of suffering and substantial incapacity, emphasizing the importance of "subthreshold psychiatry". Thus, careful observations of patients over periods of years reveal significant shifts in depression subtypes as time passes. The superimposition of categorical diagnostic classifications onto a continually changing trait may lead to a diagnostic system that fails to adequately represent the subjacent depressive condition.³⁶

Klein³⁷ compared the relatives of patients with dysthymia, of patients with MDD episodes and of normal controls with respect of the existence of a depressive personality disorder (subthreshold depression ). The results revealed that relatives of dysthymic patients had a significantly higher rate of depressive personality disorders (DPD) than did the relatives of the normal controls. Relatives of patients with MDD episodes had a rate that was intermediate between the other two groups. The author concluded that the findings reinforced the thesis that DPD is part of the spectrum of affective disorders, suggesting that this connection is particularly strong in the chronic forms of depression, such as dysthymia and double depression.³⁷

Following the same logic, Kwon et al.,³³ found significantly higher rates of dysthymic disorder development among women with DPD than in women in a control group during a 3-year follow-up study. The development of MDD was not statistically significant.³³

Flament et al.³⁸ compared phenomenology, psychosocial correlations and treatment seeking in adolescents with MDD episodes, with dysthymia, and controls. Patterns of affective symptoms were similar among the dysthymics and those with MDD episodes, with the latter having more comorbid conditions. The dysthymics had significantly worse family relationships. Dysthymic patients and those with MDD also sought few treatment environments for their conditions.³⁸

According to Akiskal,⁵ data from sleeping electroencephalogram (EEG) and abnormalities uncovered with TRH-TSH tests, among others, indicate that many people with dysthymic disorders exhibit, at baseline, the neurophysiological patterns found with acute MDD, further confirming the constitutional nature of the disorder.⁵ These data are similar to those encountered by Akiskal et al.,³⁹ who, reviewing clinical and polysomnographic data of subsyndromal conditions (or subthreshold), found a reduction in the REM phase latency of sleep, a positive response to antidepressants and sleep privation, high rates of mood disorders within the family and a longitudinal course triggering MDD. The findings, in addition to supporting the existence of a depressive spectrum, reinforce the idea that these subthreshold depressions are part of the spectrum,³⁹ since they are similar to those found in dysthymia and major depression.

Another area of study involves the relationship between dysthymia and the bipolar spectrum.^9,40-43 In this respect dysthymia is inserted into the current nosological discussion with the depression as dimensional versus categorical question on one side and the unipolar-bipolar dichotomy, on the other. Dysthymia reflects this controversy to the extent that it represents a possible trait dimensional depression on one side and a subsymptomatic depressive condition with links to bipolarity (soft bipolarity) on the other.⁴⁰ Brunello et al. suggested that, despite the typical presentation of dysthymia being unipolar, around a third of cases might be linked with the bipolar spectrum. This subtle connection with bipolarity could explain, in part, how asthenia, lethargy and low energy characterize a subset of dysthymics.⁴⁰

Nicolescu & Akiskal,⁹ describing anxious and anergic dysthymic subsets (discussed below), both of which can develop bipolarity, suggested that a more complex concept of dysthymia within the affective spectrum might include it within the bipolar spectrum.⁹ Angst et al.⁴² suggested the "minor bipolar disorder", which could include dysthymia associated with hypomanic symptoms.⁴² The so-called "bipolar dysthymia" would be characterized by a tendency towards states of elation and a family history of bipolar disorder.⁴³ In the bipolar spectrum, as described by Kraepelin at the start of the twentieth century, would be included the attenuated forms and also a large proportion of the MDD domain, while current nosology (ICD-10 and DSM-IV) is insufficient to adequately reflect this spectrum.^41,42

Dysthymia subtypes

Despite the differences between the DSM-IV and ICD-10 criteria for early and late onset dysthymic disorder^32,34 and the controversies over the relevance of such a distinction, 4 this classification is accepted, and much research^40-48 has demonstrated significant differences between the two groups. Early onset dysthymia is considered the prototype of the disorder,^19-21,45,49 and is more prevalent.^15,19,46,48 One of the most characteristic findings with early onset dysthymic disorder is an elevated incidence of Axis II comorbidities (personality disorders).^45-48 Furthermore, early onset dysthymia has higher rates of comorbidity with major depression^14,50 and anxiety disorders and there is a greater propensity towards a family history of affective disorders.^14,51

Barzega et al. studied the clinical characteristics of dysthymia with respect of age at onset and found a relationship between stressor events (disease, separations) prior to the disorder and late onset dysthymia, suggesting and etiologic link.⁴⁴ The authors also found a relationship between early onset dysthymia and comorbidities such as MDD, panic disorders and social phobias, in addition to greater disease duration.⁴⁴ Bellino et al., in a similar study,⁴⁷ also found a relationship between stressor events and late onset dysthymia. The authors found a higher rate of personality disorders in early onset dysthymics, suggesting that this type of dysthymia is more related to personality abnormalities, while late onset dysthymia would be related to stressor events (triggers).⁴⁷ In another study into the subject, Klein et al.⁴⁸ found an association between early onset and substance abuse and family history of affective disorders. Furthermore, early onset dysthymics were less likely to be married. The author suggests that early-onset dysthymia is a more severe condition that can result in maladaptative states that predispose to the development of personality disorders and substance abuse.⁴⁸

In corroboration of the hypothesis that one etiologic factor in late onset dysthymia is a reaction to stressor events, Migliorelli et al. found that 28% of a sample of patients with Alzheimer's were dysthymic, and that in more than 80% of these dysthymia had had onset after the disease.⁵²

Other dysthymia subtypes have also been proposed by several authors.^3-5,9 Serretti et al. made a study of 512 dysthymics with no MDD, delineating subtypes within the dysthymic disorder.⁴ The results demonstrated dysthymic subtypes who are sadder and more morose, but without marked difficulties with concentration, activity or energy, and also subtypes who did have these latter characteristics, but did not experience much sadness ("neurasthenic" subtype). The authors speculate that to include different degrees in the clinical construct of dysthymia could, in part, explain why different classes of antidepressants have been observed to be effective for dysthymia, supporting the hypothesis that a possible neurochemical substrate of dysthymia involves the noradrenergic, serotonergic and dopaminergic systems. Another important finding was that the anxiety characteristics, often present with dysthymia, appear to be divided into somatic and psychic types, with the latter more prevalent in dysthymia. One significant limiting factor in the work undertaken by Serretti et al. was that double depression was included in the exclusion criteria, with the result that the majority of their dysthymics were late onset, which is in agreement with the majority of research.⁴

More recently, Niculescu III & Akiskal⁹ suggested a new endophenotypic classification with two types of dysthymia. The first type, known as "anxious dysthymia", is characterized by low self-esteem and insecurity. Its etiology is related to a serotonin deficiency, and is related to a perceived stressor (a past loss or trauma, sensitizer for a future stress). These individuals are more impulsive and more often attempt suicide (although with less lethality), trying to seek help. This type is more common among women, who tend to self-medicate with anxiolytic drugs, such as benzodiazepines, marijuana, alcohol and, most often food abuse (bulimic behavior and/or weight gain). Some of these patients exhibit transformation to type II bipolar disorder.⁹

The second type of dysthymia proposed is "anergic dysthymia", characterized by low energy, low reactivity and anhedonia. This psychomotor inertia is etiologically related to low dopamine levels. These patients are more often male, have less sexual interest, are less impulsive, present hypersomnia and a reduced REM phase during sleep and tend not to seek help. A proportion of these patients tend to self-medicate, abusing stimulant drugs, such as methamphetamine, cocaine, nicotine and caffeine. Some of these patients exhibit transformation to type I bipolar disorder.⁹

Within this hypothesis, distinct biological mechanisms involved in these two types of dysthymia may respond differently to different types of antidepressants. Thus, Niculescu III & Akiskal propose that anxious dysthymia, related to low serotonin levels, respond better to selective serotonin reuptake inhibitors (SSRI). Anergic dysthymia, in contrast, which is related to low dopamine levels, responds better to dopaminergic and noradrenergic medications like bupropion, venlafaxine, stimulants and tricyclic antidepressants.⁹

COMORBIDITY WITH MAJOR DEPRESSIVE DISORDER

The term comorbidity was used by Feinstein (1970) to signify "any additional clinical entity that exists or may occur during the clinical course of a given disease".²⁵ Despite the different types of comorbidities in existence we will employ the class "clinical comorbidity", which refers to a disorder's the difference in course and response to treatment. The importance of identifying clinical comorbidity in dysthymic disorder is, among other aspects, based on the possibility of predicting prognosis and the need to establish different treatment strategies for each of morbid condition.²⁵

Major depressive disorder is the psychiatric pathology that is most frequently associated with dysthymia,²⁵ which has been proven to increase the risk of a major depressive episode.^{5,14,15,19,20,40,45,53} A majority of dysthymic patients will develop an MDD episode at some point in their lives,^14,15,45,53 and some studies show that almost all will do so.^2,19,20 It is further estimated that 40% of those patients who suffer MDD episodes will also satisfy the criteria for dysthymic disorder.^5,7 When these two pathologies are concomitant the condition is defined as "double depression" (DD).^19,20,25,54 Stressor episodes are important triggers of DD in dysthymic patients.⁵³

Patients with DD have more severe depressive symptoms,^45,55 a more chronic course and more comorbidities if compared with patients with pure MDD⁵⁵ or pure dysthymia.⁴⁵ The level of functional incapacity is greater than with patients with one of the two pathologies in isolation,²⁰ as is the rate of hospital admission⁵⁰ and MDD recurrence.⁵⁴ The rate of comorbidities such as anxiety disorders, substance abuse, personality disorders⁵⁴ and irritable bowel syndrome²⁵ are also higher with DD if compared with major depression in isolation. The recovery rate from an MDD episode is lower in patients with DD than in those with an isolated MDD episode,^14,18 and, when recovery does occur, it is incomplete in the majority of cases.¹⁸ These patients' prognosis is worse and treatment must be directed at both disorders.⁷

Pepper et al.⁴⁵ found a rate of MDD recurrence that was significantly greater among patients with DD (82.1%) than among patients com with isolated MDD episodes (62.2%).⁴⁵ The majority of the dysthymics had a previous or current history of DD, with patients with DD having a worse level of function than the pure dysthymics.⁴⁵

Tucci et al.⁵⁰ studied levels of social adjustment in different affective disorder subsets (bipolar, unipolar, dysthymia and DD).⁵⁰ Patients with DD, together with the bipolar patients, exhibited the worst levels of social adjustment. Patients with DD also presented the worst results for family relationships. Stressor events were related to onset and recurrence of all affective disorder categories. The emotional quality of the family environment was considered predictive of the course of the affective disorders.⁵⁰

The diagnostic system can influence the level of comorbidity found. The greater the number of categories that a diagnostic system includes the greater the possibility of a patient receiving more than one diagnosis. Comorbidity may only reflect excessive subdivisions.²⁵ With respect of this issue, the discussion between categorical and dimensional becomes fundamental, primarily in the distinction between dysthymia and MDD. As seen above, recent research into dysthymia emphasize its connection with the other subsyndromal forms and the full blown disease (MDD), suggesting that, within one depressive dimension or spectrum, these different forms may simply represent different degrees of the same disease on a continuum, i.e. be differences that are more quantitative than qualitative.^{15,16,19,36,44,45,56}

Despite doubts about whether the different subtypes of depression are sufficiently distinct,^16,57 DD remains an accepted diagnosis. Keller et al. reviewed the distinctions between dysthymia, MDD episodes and DD, hypothesizing that DD is a subtype of unipolar depression. The authors concluded that it is not yet possible to define DD as a subtype of major depression, suggesting that a classification that separates DD and MDD is still justified.⁵⁴

Goodman et al.⁵⁸ studied discriminating factors (and their consequences) in children and adolescents with MDD and dysthymia. Their findings did not support strong discrimination between MDD and dysthymia in the studied sample, but suggested that a combination of the two leads to more incapacity and less social competence in addition to a greater propensity towards anxiety disorders. Thus, children with DD are more apt to be seriously compromised in a number of different areas of function and to have more symptomology and greater compromise in the social and family contexts.⁵⁸

Flament et al.³⁸ compared phenomenology, psychosocial correlations and treatment seeking in adolescents with MDD episodes, dysthymics and controls. Affective symptom patterns were similar in dysthymics and in patients with MDD episodes, with the latter having more comorbid conditions. Dysthymic patients and those with MDD also sought few treatment environments for their conditions. The authors emphasize the severity of both conditions.³⁸

Klein et al.⁴⁹ assessed mood and personality disorders in first degree relatives of dysthymic patients, MDD patients and controls. The results revealed that there was a strong family relationship between dysthymia and MDD. Nevertheless, dysthymia was also mildly distinct in being aggregated specifically in families with dysthymia patients. Finally, dysthymia and MDD exhibited a family association with personality disorder, although the link was a little stronger for dysthymia.⁴⁹

Kovacs et al.,⁵⁷ in a 12 year naturalistic prospective follow up study, compared the characteristics of dysthymia with onset in childhood and MDD also with the first episodes during childhood. Dysthymia was associated with younger age at onset than MDD, and also with a greater total risk for a subsequent affective disorder, primarily MDD and bipolar disorder.⁵⁷

Riso et al.²³ reviewed six factors that have been implicated as determinants of chronic depression (both for dysthymia and chronic major depression). The authors did not find qualitative differences between chronic and acute forms of depression. Developmental factors (adversity during childhood) were the most significant findings linked to chronicity of depression. Thus, the development of chronic depression involves an increased level of adversity during childhood, environments creating protracted stress and increased reactivity to stress.²³

In a simple comparison with episodic MDD, dysthymia appears to be an entity with greater severity. Klein et al., in a five year naturalistic prospective follow up study, described some of their results over the course of dysthymic disorder.¹⁹ The estimated recovery from dysthymic disorder within 5 years was 53.9%. The estimated risk of relapse among those who had recovered was 45.2%. Patients with dysthymia fulfilled all criteria for some type of affective disorder for approximately 70% of the follow up period. During the follow up, patients with dysthymia exhibited significantly higher levels of symptoms and lower functioning and were significantly more likely to attempt suicide and be admitted to hospital than were patients with episodic MDD. The estimated risk of an initial MDD episode during the 5 years was 76.9% for the dysthymic patients. The authors concluded that dysthymia is a chronic condition with a prolonged course and a high rate of relapse. Almost all of the dysthymia patients eventually developed superimposed MDD. Although patients with dysthymic disorders tend to present mild to moderate symptoms, over a longitudinal perspective the condition is a severe one.¹⁹

DISCUSSION

Much of modern thought about mood disorders returns to concepts of the ancient Greeks.⁸ These concepts evolved for many centuries and are the fundamental basis for the evolution of psychiatry. They were not, however, postulated randomly. As Lopes⁵⁹ points out, the concepts of nosological entities on which they are based (most solidly with Kraepelin, Freud and Schneider, among others) were not established arbitrarily. They are the products of a whole accumulation of observations, reflections and relationships with patients. Nowadays many articles are returning to these works which, in particular those of Kraepelin, were fundamental to the current concept of dysthymia. Kraepelin's idea of a continuum model within the spectrum of depressive disorders is one of the primary foci of study of contemporary authors, demonstrating how important historical contributions can be to the evolution of psychiatry.

Historico-nosological study of dysthymia has had fundamental practical importance to the clinical unfolding of this entity. Once considered a personality disorder, with a range of therapeutic limitations, today dysthymia is classified as an affective disorder, which has widened the therapeutic arsenal and changed prognosis. Furthermore, this evolution has also amplified discoveries of its clinical characteristics and opened the way for promising theories with respect of its etiology, also contributing towards a better understanding of the mood disorder spectrum.

Despite the elevated morbidity, until the 80s little research had been done into alternative treatments for dysthymia: it was considered a personality disorder refractive to antidepressant therapy.⁷ It appears that nowadays there is no longer any doubt that the inclusion of dysthymia within the mood disorders represents a great advance in the treatment of chronically depressed patients.⁶⁰ They are now treated within the therapeutic perspective of the affective diseases, resulting in increased interest in pharmacological approaches to the treatment.^40,60

Studies show that 50 to 60% of patients with dysthymia respond to treatment with antidepressants.^61,62 monoamine oxidase inhibitors (MAOI), tricyclic antidepressants (ADT) and SSRI are effective for dysthymia treatment.^40,61,63,64 Studies of homeopathy and hormone replacement are still lacking.^65,66 The treatment that is most accepted nowadays considered most effective is a combination of pharmacotherapy with psychotherapy, primarily cognitive and behavioral.^6,7,40

The large number of studies that have been made of dysthymia, however, are still lacking in methodological standardization. Almost all of the clinical studies reviewed in the present article report methodological limitations, which makes it difficult to generalize the results. These limitations, in addition to the peculiarities of each study, can be attributed to the current difficulties in adopting a standard concept of dysthymic disorder. The official classifications themselves (ICD-10 and DSM-IV) are based on different diagnostic criteria. On the other hand, these differences do not impede many results from repeating and, little by little, giving dysthymia a "new face". More detailed studies, with standardized concepts and criteria, are needed in order that this disorder, so prevalent and costly, can be better understood and treated.

CONCLUSIONS

Dysthymic disorder is a significant cause of morbidity that is very prevalent in our country and that greatly increases the costs and the usage of the health system. The concept of dysthymia, originally wide ranging and non-specific, has undergone many modifications over the years, and is nowadays included among the affective disorders within the chronic depression spectrum. The new nosological classification represents an important step towards a better understanding of the entity in addition to a pharmacological approach to its treatment. Nowadays the relationship between dysthymia and the other mood disorders, particularly MDD, is the subject of much study and many controversies. Current studies remain methodologically limited, which is also the fruit of the lack of standardization of the description of the disorder. Because of its importance, further studies with criteria-based methodologies and considerable samples should be stimulated so that we can better understand and treat this disorder.

REFERENCES

Received on August 24, 2004.

Revised on October 19, 2004.

Approved on November 9, 2004.

• 1. Akiskal HS. Dysthymia and cyclothymia in psychiatric practice a century after Kraepelin. J Affect Disord 2001;62:17-31.
• 2. Akiskal HA, Costa e Silva AJ, Frances A, Freeman HL, Keller MB, Lapierre YD, et al. Dysthymia in clinical practice. Br J Psychiatry 1995;166:174-83.
• 3. Griffiths J, Ravindran AV, Merali Z, Anisman H. Dysthymia: a review of pharmacological and behavioral factors. Mol Psychiatry 2000;5:242-61.
• 4. Serretti A, Jori MC, Casadei L, Ravizza L, Smeraldi E, Akiskal H. Delineating psychopathologic clusters within dysthymia: a study of 512 out-patients without major depression. J Affect Disord 1999;56:17-25.
• 5. Akiskal HS. Dysthymia: clinical and external validity. Acta Psychiatr Scand 1994;89(suppl 383):19-23.
• 6. Nardi AE. Estudo epidemiológico em distimia. J Bras Med 1999;77(1):85-96.
• 7. Kaplan HI, Sadock BJ, Grebb JA. Compêndio de psiquiatria. 7Ş ed. Porto Alegre: Artes Médicas; 1997.
• 8. Akiskal HS. Mood disorders. In: Sadock BJ, Sadock VA, eds. Kaplan & Sadock's Comprehensive textbook of psychiatry. 7th ed. Philadelphia: Library of Congress; 1999. vol. 1.
• 9. Niculescu III AB, Akiskal HS. Proposed endophenotypes of dysthymia: evolutionary, clinical and pharmacogenomic considerations. Mol Psychiatry 2001;6:363-6.
• 10. Nesse RM. Is depression an adaptation? Arch Gen Psychiatry 2000;57(1):14-20.
• 11. Kornstein SG. Chronic depression in women. J Clin Psychiatry 2002;63:602-9.
• 12. Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI et al. Gender differences in chronic major and double depression. J Affect Disord 2000;60:1-11.
• 13. Niculescu AB, Akiskal HS. Sex hormones, Darwinism, and depression. Arch Gen Psychiatry 2001;58(1):1083-4.
• 14. Keller MB. Course, outcome and impact on the community. Acta Psychiatr Scand 1994;89(suppl 383):24-34.
• 15. Avrichir BS, Elkis H. Prevalence and underrecognition of dysthymia among psychiatric outpatients in São Paulo, Brazil. J Affect Disord 2002;69:193-9.
• 16. Akiskal HS. Dysthymia as a temperamental variant of affective disorder. Eur Psychiatr 1996;11(suppl 3):117s-22s.
• 17. Katon W, Russo J, Frank E, Barrett J, Williams JW, Oxman T, et al. Predictors of nonresponse to treatment in primary care patients with dysthymia. Gen Hosp Psychiatry 2002;24:20-7.
• 18. Nardi AE, Saboya E, Pinto S, Figueira I, Marques C, Mendlowicz M, et al. Distimia: aspectos clínico-terapêuticos. J Bras Psiq 1993;42(7):357-72.
• 19.Klein DN, Schwartz JE, Rose S, Leader JB. Five-year and outcome of dysthymic disorder: a prospective, naturalistic follow-up study. Am J Psychiatry 2000;157:931-9.
• 20. Hayden EP, Klein DN. Outcome of dysthymic disorder at 5-year follow-up: the effect of familial psychopathology, early adversity, personality, comorbidity, and chronic stress. Am J Psychiatry 2001;158:1864-70.
• 21.Lizardi H, Klein DN. Parental psychopathology and reports of the childhood home environment in adults with early-onset dysthymic disorder. J Nerv Ment Dis 2000;188(2):63-70.
• 22. Gilmer WS, McKinney WT. Early experience and depressive disorders: human and primate studies. J Affect Disord 2003;75:97-113.
• 23. Riso LP, Miyatake RK, Thase ME. The search for determinants of chronic depression: a review of six factors. J Affect Disord 2000;70:103-15.
• 24. Westermeyer J, Eames SL, Nugent S. Comorbid dysthymia and substance disorder: treatment history and cost. Am J Psychiatry 1998;155(11):1556-60.
• 25. Moreno RA, Moreno DH. A relação entre outros quadros psiquiátricos e distimia. In: Cordás TA, Nardi AE, Moreno RA, Castel S, orgs. Distimia — do mau humor ao mal do humor. Porto Alegre: Artes Médicas; 1997. p.42-52.
• 26. Freeman HL. Historical and nosological aspects of dysthymia. Acta Psychiatr Scand 1994;89(suppl 383):7-11.
• 27. Cordás TA. Depressão: da bile negra aos neurotransmissores — uma introdução histórica. São Paulo: Lemos; 2002.
• 28. Cordás TA. Do mal-humorado ao mal do humor — uma perspectiva histórica. In: Cordás TA, Nardi AE, Moreno RA, Castel S, orgs. Distimia — do mau humor ao mal do humor. Porto Alegre: Artes Médicas; 1997. p.15-21.
• 29. Cordás TA, Taveira A. Oxcarbazepina no transtorno bipolar do humor. São Paulo: Lemos; 2003.
• 30. Alcantara I, Schmitt R, Schwarzthaupt AW, Chachamovich E, Sulzbach MFV, Padilha RTL, et al. Avanços no diagnóstico do transtorno do humor bipolar. Rev Psiquiatr RS 2003;25(supl 1):22-32.
• 31. Nardi AE, Cordás TA. Distimia e personalidade. In: Cordás TA, Nardi AE, Moreno RA, Castel S, orgs. Distimia — do mau humor ao mal do humor. Porto Alegre: Artes Médicas; 1997. p.53-67.
• 32. Lopez Ibor JJ, Frances A, Jones C. Dysthymic disorder: a comparison of DSM-IV and ICD-10 and issues in differential diagnosis. Acta Psychiatr Scand 1994;89(suppl 383):12-8.
• 33. Kwon JS, Kim YM, Chang CG, Park BJ, Kim L, Yoon DJ, et al. Three-year follow-up of women with the sole diagnosis of depressive personality disorder: subsequent development of dysthymia and major depression. Am J Psychiatry 2000;157(12):1966-72.
• 34. Castel S, Scalco MZ. Distimia: quadro clínico e diagnóstico. In: Cordás TA, Nardi AE, Moreno RA, Castel S, orgs. Distimia — do mau humor ao mal do humor. Porto Alegre: Artes Médicas; 1997. p.23-41.
• 35. Anderson RL, Klein DN, Riso LP, Ouimette PC, Lizardi H, Schwartz JE. The subaffective-character spectrum subtyping distinction in primary early-onset dysthymia: a clinical and family study. J Affect Disord 1996;38:13-22.
• 36. Angst J, Merikangas K. The depressive spectrum: diagnostic classification and course. J Affect Disord 1997;45:31-40.
• 37. Klein DN. Depressive personality in the relatives of outpatients with dysthymic disorder and episodic major depressive disorder and normal controls. J Affect Disord 1999;55:19-27.
• 38. Flament MF, Cohen D, Choquet M, Jeammet P, Ledoux S. Phenomenology, psychosocial correlates, and treatment seeking in major depression and dysthymia of adolescence. J Am Acad Child Adolesc Psychiatry 2001;40(9):1070-8.
• 39. Akiskal HS, Judd LL, Gillin C, Lemmi H. Subthreshold depressions: clinical and polysonographic validation of dysthymic, residual and masked forms. J Affect Disord 1997;45:53-63.
• 40. Brunello N, Akiskal H, Boyer P, Gessa GL, Howland RH, Langer SZ, et al. Dysthymia: clinical picture, extent of overlap with chronic fatigue syndrome, neuropharmacological considerations, and new therapeutic vistas. J Affect Disord 1999;52:275-90.
• 41. Akiskal, HS. Validating 'hard' and 'soft' phenotypes within the bipolar spectrum: continuity or discontinuity? J Affect Disord 2003;73:1-5.
• 42. Angst J, Gamma A, Benazzi F, Ajdacic V, Eich D, Rössler W. Toward a re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. J Affect Disord 2003;73:133-46.
• 43. Angst J. Dysthymia and personality. Eur Psychiatry 1998;13:188-97.
• 44. Barzega G, Maina G, Venturello S, Bogetto F. Dysthymic disorder: clinical characteristics in relation to age at onset. J Affect Disord 2001;66:39-46.
• 45. Pepper CM, Klein DN, Anderson RL, Riso LP, Ouimette PC, Lizardi H. DSM-III-R axis II comorbidity in dysthymia and major depression. Am J Psychiatry 1995;152:239-47.
• 46. Garfallos G, Adamopoulou A, Karastergiou A, Voikli M, Sotiropoulou A, Donias S, et al. Personality disorders in dysthymia and major depression. Acta Psychiatr Scand 1999;99(5):332-40.
• 47. Bellino S, Pátria L, Ziero S, Rocca G, Bogetto F. Clinical features of dysthymia and age: a clinical investigation. Psychiatry Res 2001;103:219-28.
• 48. Klein DN, Schatzberg AF, McCullough JP, Keller MB, Dowling F, Goodman D, et al. Early- versus late-onset dysthymic disorder: comparison in out-patients with superimposed major depressive episodes. J Affect Disord 1999;52:187-96.
• 49. Klein DN, Riso LP, Donaldson SK, Schwartz JE, Anderson RL, Ouimette PC, et al. Family study of early-onset dysthymia. Arch Gen Psychiatry 1995;52:487-96.
• 50. Tucci AM, Kerr-Corrêa F, Dalben I. Ajuste social em pacientes com transtorno afetivo bipolar, unipolar, distimia e depressão dupla. Rev Bras Psiquiatr 2001;23(2):79-87.
• 51. Devanand DP, Adorno E, Cheng J, Burt T, Pelton GH, Roose SP, et al. Late onset dysthymic disorder and major depression differ from early onset dysthymic and major depression in elderly outpatients. J Affect Disord. (In press.).
• 52. Migliorelli R, Tesóm A, Sabe L, Patracchi M, Leiguarda R, Starkstein SE. Prevalence and correlates of dysthymia and major depression among patients with Alzheimer's disease. Am J Psychiatry 1995;152:37-44.
• 53. Moerk KC, Klein DN. The development of major depressive episodes during the course of dysthymic and episodic major depressive disorders: a retrospective examination of live events. J Affect Disord 2000;58:117-23.
• 54. Keller MB, Hirschfeld RMA, Hanks D. Double depression: a subtype of unipolar depression. J Affect Disord 1997;45:65-73.
• 55. Goodman AH, Schwab-Stone M, Lahey B, Shaffer D, Jensen P. Major depression and dysthymia in children and adolescents: discriminant validity and differential consequences in a community sample. J Am Acad Child Adolesc Psychiatry 2000;39(6):761-70.
• 56. Klein DN, Kocsis JH, McCullough JP, Holzer III CE, Hirschfeld RMA, Keller MB. Symptomatology in dysthymic and major depressive disorder. Psychiatr Clin N Am 1996;19(1):41-53.
• 57. Kovacs M, Akiskal HS, Gatsonis C, Parrone PL. Childhood-onset dysthymic disorder. Arch Gen Psychiatry 1994;51:365-74.
• 58. Goodman SH, Schwab-Stone M, Lahey BB, Shaffer D, Jensen P. Major depression and dysthymia in children and adolescents: discriminant validity and differential consequences in a community sample. J Am Acad Child Adolesc Psychiatry 2000;39(6):761-70.
• 59. Lopes CB. Desafios éticos atuais na psiquiatria. Bioética 2001;9(1):29-43.
• 60. Lima MS. Tratamento farmacológico da distimia: avaliação crítica da evidência científica. Rev Bras Psiquiatr 1999;21(2):128-30.
• 61. Ravindran AV, Anisman H, Merali Z, Charbonneau Y, Telner J, Robert B, et al. Treatment of primary dysthymia with group cognitive therapy and pharmacotherapy: clinical symptoms and functional impairments. Am J Psychiatry 1999;156(10):1608-17.
• 62. Williams JW, Barrett J, Oxman T, Frank E, Katon W, Sullivan M, et al. Treatment of dysthymia and minor depression in primary care: a randomized controlled trial in older adults. JAMA 2000;284(12):1519-26.
• 63. Akiskal H. Transtornos distímicos — entrevista com Hagop Akiskal. Arq Bras Med 1994;68(6):400-1.
• 64. Lima MS, Hotoph, M, Wessely S. The efficacy of drug for dysthymia: a systematic review and meta-analysis. Psychol Med 1999;29(6):1273-89.
• 65. Rudas S, Schmitz M, Pichler P, Baumgartner A. Treatment of refractory chronic depression and dysthymia with high-dose thyroxine. Biol Psychiatry 1999;45:229-33.
• 66. Seidman DN, Araujo AB, Roose SP, Devanand DP, Xie S, Cooper TB, et al. Low testosterone levels in elderly men with dysthymic disorder. Am J Psychiatry 2002;159:456-9.

Publication Dates

• Publication in this collection
  14 Sept 2005
• Date of issue
  Dec 2004

History

• Accepted
  09 Nov 2004
• Reviewed
  19 Oct 2004
• Received
  24 Aug 2004