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Dysthymia and major depressive disorder - Spanemberg & Juruena Review Article Dysthymia: historical and nosological characteristics and

its relationship with major depressive disorder Lucas Spanemberg * Mario Francisco Juruena ** INTRODUCTION dysthymia is a chronic form of depression, non-episodic, less sever e symptomatology than those called major depression 1-4. The basic pattern of th ese patients is a low degree of symptoms, which appear insidiously in most cases before 25 years.5. Despite the milder symptoms, chronicity and lack of recognit ion of the disease causes the loss of quality of life of patients is considered greater than in other types of depression 6. Patients with dysthymic disorder ar e often sarcastic, nihilistic, grumpy, demanding, and complainants. They may be tense, rigid and resistant to therapeutic interventions, although regularly atte nd to queries. As a result * Medical Student Foundation Federal School of Medical Sciences of Porto Alegre (FFFCMPA). ** Psychiatrist, Visiting Professor at the Institute of Psychiatry, K ing's College School of Medicine, University of London, Associate Specialist, So uth London Maudsley Trust, UK. addition, the doctor may feel angry with the patient and even disregard their qu eixas7. Although the disorder present with a relatively stable social functionin g, this stability is relative, since many of these patients who have invested en ergy in work, nothing left for pleasure and family activities and social, leadin g to marital friction característico8. In evolutionary terms, dysthymia may be a n adaptive subtype of humor that was developed to address states of stress or de privation 9. Thus, certain characteristics of depressed mood might confer evolut ionary advantages under specific conditions (where the lack of action and initia tive would be more appropriate to avoid danger to life) 10, being beneficial in certain subpopulations and settings, selecting them over time. As a condition ma ladaptive, dysthymia is clinically manifested as a departure from routine daily activities rather than face them. Differences gênero11, 12 - female dominance in dysthymia and major depression may also have a reason evolucionária9, 13. 300 Received on 24/08/2004. Revised on 19/10/2004. Approved em 09/11/2004. R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena The prevalence of dysthymia is approximately 3-6% of the general population 4-6, 14,15, one of the conditions most commonly encountered in practice médica5. Thes e patients do not seek help or support 2,3,6 for a long period and their symptom s usually consult clinicians with ill-defined complaints such as malaise, lethar gy and fadiga5, 16. About 50% of these patients will not be recognized by clínic os1, 2.17, and most will present a series of comorbidades3, 5.14. Just as major depressive disorder (MDD), dysthymia is twice as common in women than in homens1 ,6,11-13, and is also more common in people solteiras18-20. When married, these people have unsatisfactory relationships. Poliqueixosas and are also dissatisfi ed with vida16. The etiology of dysthymia is complex and multifactorial, being i nvolved biological and psychological etiological mechanisms. These multiple fact ors - heredity, predisposition, temperament, lifestyle factors, biological stres sors, gender, etc.. - Converge in the production of deregulation of the reward s ystem in August. Stressful life events in childhood 20-23 are frequent. As dysth

ymia is associated with an increased use of health services and also to increase d consumption of psychotropic drugs, huge financial costs can be attributed to t his transtorno14, 17.24. Decreased productivity at work and an increased risk of hospitalização14, 19 and physical illnesses (such as increased risk of cardiova scular and respiratory diseases) 14 also increase the economic and social cost o f this pathology, making it a public health problem that needs to be identified more efficiently. The high rate of comorbidity with other psychiatric disorders (about 77% of dysthymic have comorbidities) 25 makes it even more important to t he diagnosis of dysthymia for the appropriate management of comorbid psychopatho logy. This article aims to review the major historical and nosological aspects o f this disorder, as well as its relationship with the TDM. We will discuss their subtypes, controversies regarding the categorical versus dimensional distinctio n of dysthymia and its relationship with other mood disorders. For this,€were se lected for convenience, the most relevant articles in the databases LILACS and MEDLINE. In the end, we discuss the relevance of the topic and its im portance in the practice of psychiatry today. The terms "dysthymic disorder" and "dysthymia" are used interchangeably, since both are widely used at present. HI STORICAL FEATURES The term "dysthymia" is from Ancient Greek and means "bad mood " 1.26. Hippocratic Greek at school, she was considered as part of the concept o f melancholia, a term derived from the temperament or character typical of intox ication or influence of "black bile", one of four "humors fundamental" 1,27,28. Thus, individuals lethargic, anxious and insecure were prone to a temper melancó lico1. Galen of Pergamum (128-201 AD) describes the melancholy and introspective , pessimistic and bodily magros27 - "if fear or depression lasts a long time, th is state is very melancholy," said Galeno29. He established melancholy as a chro nic and recurrent condition, which could be a primary disease of the brain or se condary to other doenças30. Sorano of Ephesus describes melancholic patients wit h symptoms of injury, and paranoid depressivos27. From Ancient Greece to the Mid dle Ages, mental illness was cared for by clerics and religious, since it has to be attributed to magic, sin and demonic possession, Santa Inquisição30 target. At the same time, the Arab world was important readings and descriptions of the concept of melancholy, by Avicenna (980-1037), Maimonides (1135), Averroes (1126 ) and Constantine (1019-1087), among outros27. During the Renaissance, Robert Bu rton publishes The Anatomy of Melancholy (1621). In this work, Burton's list amo ng the causes of melancholy, advanced age, temperament and heritage, and also es tablishes it as a secondary cause of disease corpo27. In the 18th century, Willi am Cullen (1710-1790), influenced the Enlightenment, the melancholy associated w ith a primary instability of the brain and suggests "restrictions" as the best r emedy to reduce excitação27. The 19th century brings an increasing interest in m inor forms of mood disorders (folie round), which, according Falret (18,241,902) , a trained observer would perceive as a continuum of disease maior28. Falret wr ites about ways 301 R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena 302 attenuated disease circular, and later, in 1863, Karl Ludwig Kahlbaum uses the t erm "cyclothymia" to the milder forms of mood fluctuations and "dysthymia" to th e forms of the disease (melancholia) that show only one depressed atenuada26 28. The description in 19th century Germany, seems to have been the first approach to the meaning of the term of mild chronic depression, not a psychopathic temper ament depressivo28. The term "depression" begins to appear in medical dictionari es em1860, being widely accepted and increasingly restricting the term 'melancho ly' 27. Esquirol (1772-1840) suggests that the word "melancholy" is left to the

use of poets. Berrius scholar of the history of psychiatry shows that the term " depression" has supplanted the ancient "melancholy" in the light of the apparent physiological and metaphorical impression of the functions that fall sugeria27. Emil Kraepelin described in 1921, the relationship between temperament and depr essive manic-depressive insanity, suggesting that the first would be an attenuat ed form, but belonging to the same constellation of pathologic disease plena18, 26,28, a model of continuum5, 7. The characteristics of the depressive temperame nt would be the constant presence, though fluctuating, sadness, anxiety, pessimi sm and lack of pleasure 28. Kraepelin advocated a sort of mental illness grounde d in the natural history of patients and the evolutionary course of their disord ers, psychiatric symptoms before their 26th. He therefore developed the concept of nosological status and mood disorders grouped under the aegis of manic-depres sive insanity, separating them from dementia praecox (schizophrenia) 7.27. This proposed dichotomy is still the strongest force in psiquiatria27 taxonomic conce pt. In 1923, Kurt Schneider, in his monograph, described the 26 or dysthymic dep ressive psychopathy, linking it to mix the etiology of hereditary factors, neona tal and early environmental influences - and not a disease of mood (depression) 18. Using the term "personality," Schneider defined as abnormal personalities so me variants of the constitutional standard, considering thus psychopathy in the field of depressive disorders personalidade31. Kretschmer, 1936,€strengthened th e idea of continuity between the basic temperament and disease, leading it to it s utmost importance. He opposed the concept of unity Kraepelin's nosological and introduced the so-called dimensional diagnosis, as o pposed to categorical kraepeliniano27. Under the influence of psychoanalytic the ories and schneiderian, the American official classifications (Diagnostic and St atistical Manual of Mental Disorders - DSM-II, 1968) and worldwide (Internationa l Classification of Diseases - ICD9, 1978) spread the idea of chronic depression as equivalent to neuroses character, deviating from mood disorders and linking it to the 18 personality disorders. Thus, in the 60s and 70s, the DSM-II include d "Neurotic Depression," and ICD-9, "depressive neurosis", but both episodes enc ompassed non-crônicos26. However, the view that personality disorders were not t reatable represent an insurmountable conceptual problem, becoming more complex b y the fact that the existence of normal personality traits with abnormal variant s did not represent necessarily a disorder psiquiátrico26. Thus, in 1978, Akiska l et al. published a follow-up study 3-4 years with 100 neurotic depression, she found no clinical significance in diagnosis of neurotic depression. The monitor ing of patients showed a wide variety of nosological diagnoses, both from other forms of mood disorder as other patologias18, 26.27. The many nosological diagno ses found by Akiskal et al. did conclude that the diagnosis of neurotic depressi on had no phenomenological features themselves sufficient to constitute a distin ct nosological entity 18. This represented an important support in establishing the empirical basis of dysthymia in the sense atual26 and was a landmark in the history nosological of mood disorders. Under the influence of new discoveries in the DSM-III, chronic depression is now referred to by the term "Dysthymic Disor der" to replace "neurotic depression" in DSMII, and is included in the chapter o n affective disorders. Despite the descriptive model called "atheoretical" as th e aetiology (operationalized), this position marks the expulsion of chronic depr essions in the field of disorders of character and personality. Despite these de velopments, dysthymic disorders has encompassed a wide variety of entities such as primary depressions with residual chronicity, chronic dysphoria, and secondar y depressions R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena characterological (personality disorder and dysthymic disorder itself) 18. The D SM-III-R and DSM-IV incorporated some of these definições26, and, in the appendi x to DSM-IV, already appears depressiva1 personality disorder, 32,33. The ICD-10

does not establish a concept of dysthymia that is essentially different from de pressive neurosis or neurotic depression 26, ie it is a broader concept than the DSM-IV. The differences between the diagnostic criteria of both manuals reflect , among other things, the fact that the DSM-IV is intended also for research, wh ile the ICD-10 is intended for clinical application. Moreover, the political com position of the ICD-10 is much more complex, because he wants to embrace the who le world, not just a país32, 34. Both, despite their differences, consider dysth ymia as an affective disorder, unipolar, chronic (at least 2 years) with early o r late, with symptoms less intense than that observed in a depressive episode, w ith symptoms including insomnia, Low energy and fatigue, low self-esteem, decrea sed ability to concentrate and loss of interest and prazer34. Today, like Kraepe lin described 100 years ago, it is accepted that dysthymia is an attenuated vari ant of the spectrum of affective disorders. Nowadays, dysthymia may be regarded as a less severe form of depression that increases the risk for depression maior 3. Its main features are chronicity of symptoms of low intensity (for at least t wo years), insidious onset and early course and intermittent persistente8. The c urrent nosologic aspects nosography officer ranks dysthymia as a mood disorder, differing from TDM to be chronic and less severa3, 4.8. The profile of dysthymic disorder shows a tendency to a predominance of symptoms on the signs (hollows m ore subjective than objective), another difference from TDM2, 7. Serretto et al. 4 in a study with 512 dysthymic without MDD, found cognitive and emotional sympt oms as more typical than vegetative and psychomotor symptoms. Low self-esteem, a nhedonia, fatigue,€irritability and poor concentration were present in more than half of patients 4. So, there stood out the marked disturbances in appetite and libido or observed psicomotor2 agitation or retardation. Since the patients who seek treatment often float in and out of a m ajor depressive episode, the essence of DSM-IV criteria for dysthymic disorder t ends to emphasize the vegetative dysfunction, whereas the alternative criterion B for dysthymic disorder in appendix of DSM-IV symptoms cognitivos8 list. This a lternative classification for dysthymia aims to stimulate further characterizati on of the disorder in relation to other disorders humor14. The essential standar ds of dysthymic disorder usually include sadness, lack of enjoyment of life and concern for the inadequacy. The disorder is best considered as a depression of l ow intensity, buoyant and durable, experienced as part of the usual self and rep resents an intensification of depressive temperament traits observed in the (sub liminal) 2.8. The dysthymic disorder can therefore be seen as a more symptomatic (or injunction) of temperament (depressive personality disorder) 8. This speaks in favor of the model spectrum of severity of depression, where the different f orms of depression exist along a continuum between the disease and subsyndromal forms plena25. Akiskal is the best contemporary author who has studied the hypot hesis of dimensional relationship between personality disorders and humor25, 35. This model, originally conceived by Kraepelin, suggests that subthreshold depre ssive symptoms may in fact represent the most common expressions of the disorder depressivo8. Some authors have made important contributions on the subject. Ang st & Merikangas36 in a longitudinal study of 15 years of follow-up with 591 indi viduals, investigated the application of diagnostic criteria for preliminary cat egories (MDD and dysthymia) and subthreshold depression. The main conclusions af ter the end of follow-up reinforces the idea of a depressive spectrum. Prevalenc e of categories of injunctions and subthreshold depression were similar, with ap proximately 17% of the general population meeting criteria for any category of d epression over time. Few individuals with depression met criteria for only one s ubtype of depression after 15 years - that is, there were few subtypes "pure." S ubthreshold depressions associated 303 R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena

304 with a greatly increased risk of subsequent development of MDD (strong predictor for depression), with approximately half of the subjects eventually develop maj or depression. TDM was also associated with increased risk of developing subthre shold depression, with half of individuals with MDD meeting criteria for subthre shold categories of depression during follow-up. During follow-up, dysthymic had a higher rate of hospitalization (11% versus 7%) and were treated more often fo r depression (77.8% versus 54.7%) than patients with episodes of MDD. Patients w ith recurrent brief depression also had a higher rate of treatment (60.6%) than patients with episodes of TDM36. Angst was the introducer of the term "psychiatr y injunction", which refers to the classification categories used in psychiatric diagnostic manuals like DSM-IV, which he said did not take sufficient account o f the depressive dimension. Based on epidemiological studies, Angst justifies so me disorders that fail to meet the diagnostic criteria bring contemporary levels of subjective distress and substantial disability, highlighting the importance of "subliminal psychiatry." Thus, careful observations of patients after years s how substantial changes in the subtypes of depression over time. The superpositi on of a categorical diagnostic classification on the dash constantly changing ca n lead to a diagnostic system that fails to adequately represent the depressive spectrum subjacente36. Klein compared 37 relatives of patients with dysthymia, w ith episodes of MDD and normal controls in relation to the existence of depressi ve personality disorder (depression subliminal). The results showed that relativ es of dysthymic patients had a significantly higher rate of depressive personali ty disorder (TPD) that relatives of normal controls. Relatives of patients with episodes of MDD had a rate intermediate between the other groups. The author con cludes that this finding strengthens the argument that the DPT is part of the sp ectrum of mood disorders,€suggesting that this link is particularly strong in ch ronic forms of depression such as dysthymia and depression dupla37. In the same vein, Kwon et al. 33, a follow-up study three years, they found sign ificantly higher rates of development of dysthymic disorder in women with TPD th an in women in the control group. The development of MDD was not statistically s ignificativo33. compared Flament et al. 38 Phenomenology, psychosocial correlate s and seeking treatment in adolescents with episodes of MDD, dysthymic and contr ol subjects. Patterns of affective symptoms were similar in patients with dysthy mic and MDD episodes, and the latter had more comorbid conditions. Dysthymic had significantly worse family relationships. Patients with MDD and dysthymic few e nvironments also sought treatment for their condições38. According to Akiskal 5, data from the electroencephalogram (EEG) during sleep and abnormalities in the TRH-TSH tests, among others, indicate that many people with dysthymic disorder e xhibit, as baseline, the neurophysiological pattern found in acute MDD, confirmi ng yet more in the nature of the constitutional transtorno5. These data are simi lar to those found by Akiskal et al. 39, who, reviewing clinical data and polyso mnographic of depressive conditions less-than-syndromic (or subliminal), a decre ase in latency during REM (rapid eye movements) sleep, positive response to anti depressants and sleep deprivation, high rates of disorders mood in the family an d longitudinal course triggering TDM. The findings, thus supporting the existenc e of the depressive spectrum, reinforcing the idea that these subthreshold depre ssions 39 are part of the spectrum, since they are similar to those found in dys thymia and major depression. Another area of study involves the relationship wit h the spectrum of dysthymia bipolar9 0.40 to 43. In this regard, dysthymia is in serted in the current discussion between the nosological classification of depre ssion as dimensional versus categorical one side and the unipolar-bipolar dichot omy of the other. The dysthymia reflects this controversy in that it represents a possible stroke or depression dimensional on one side and a depressive conditi on subsintomática dial with bipolarity (soft bipolar) from outro40. Brunello et al. suggest that despite the typical presentation of dysthymia to be unipolar in shape, about one third of cases could be linked to the bipolar spectrum. This s

ubtle connection with bipolarity may explain, in part, as R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena asthenia, lethargy and low energy characterize a subgroup of distímicos40. Nicol escu & Akiskal September, describing anxious and anergic subtypes of dysthymic ( discussed later), both with the possibility of bipolar processing, suggest a mor e complex conceptualization of dysthymia within the affective spectrum can inclu de it within the bipolar spectrum 9. Angst et al. 42 suggest the term "bipolar d isorder minor", which can include symptoms associated with dysthymia hipomaníaco s42. The so-called "bipolar dysthymia" was characterized by a tendency to states of elation and family history of bipolar disorder 43. In the bipolar spectrum, like Kraepelin described in the early 20th century, would be included and also a ttenuated forms much of the area of TDM, and current nosology (ICD-10 and DSM-IV ) is insufficient to adequately reflect this espectro41, 42 . Subtypes of dysthymia Despite the differences between the DSM-IV and ICD-10 for early and late onset o f dysthymic disorder and 32.34 of the controversy regarding the relevance of thi s distinção4, this classification is accepted, and many studies have shown diffe rences 44-48 significant between the two groups. The early-onset dysthymia is co nsidered the prototypical disorder 19-21,45,49, 15,19,46,48 being more prevalent . One of the most characteristic findings is the increased incidence of comorbid axis II (personality disorders) in dysthymic disorder of early precoce45-48. Ea rly-onset dysthymia also has higher rates of comorbid depression maior14, 50 and anxiety disorders and a greater propensity for family history of affective diso rders 14.51. Barzega et al. studied clinical characteristics of dysthymia in the age of onset, no relationship between stressful life events (illness, separatio n) prior to the disorder and late-onset dysthymia, suggesting a link etiológica4 4. The authors found, also, the relationship between early onset of dysthymia an d comorbid conditions such as MDD, panic disorder and social phobia, and a longe r duration of illness 44. Bellino et al., A similar study 47,€also found a relat ionship between stressful life events and late-onset dysthymia. The authors foun d a higher rate of personality disorders in early onset dysthymic, suggesting th at this type of dysthymia is more related to personality abnormalities, whereas dysthymia would be related to late events (triggers) estressores47. In another study on the issu e, Klein et al. 48 found an association between early onset with substance abuse and family history of affective disorders. Furthermore, early-onset dysthymic w ere less likely to be married. The author suggests that early-onset dysthymia is a severe condition that can result in maladaptive states that predispose to the development of personality disorders and abuse of substâncias48. Corroborating the hypothesis of a reaction to stressful events as etiological factor of late-o nset dysthymia, Migliorelli et al. found a rate of 28% in a sample of dysthymic patients with Alzheimer's, and, in more than 80% of these, dysthymia began after the doença52. Other subtypes of dysthymia have been proposed by others3-5, 9. S erretto et al., A study of 512 dysthymic without TDM, delineated subtypes within the distímico4 disorder. The results showed that dysthymic subtypes are more su bdued and slow, but without marked difficulties in concentration, activity or en ergy, and also subtypes with a predominance of these features, but on the other hand, do not experience much sadness (subtype "hipped"). The authors speculate t hat the different degrees in clinical construct of dysthymia may partly explain why different classes of antidepressants have been observed to be effective in d ysthymia, supporting the hypothesis that the possible neurochemical substrate of dysthymia systems involves noradrenergic, serotonergic and dopamine. Another im portant finding is that the characteristics anxious, very present in dysthymia, appear divided into somatic and psychic types, the latter being more prevalent i

n dysthymia. A significant limiting factor of the work of Serretto et al. is the double depression as an exclusion criterion, making it the most were late-onset dysthymic, which goes against the majority of trabalhos4. More recently, Nicule scu III & Akiskal9 endophenotypes suggested a new classification, with two types of dysthymia. The first type, called "anxious dysthymia, is characterized by lo w self-esteem and insecurity. Its etiology is related to deficiency of serotonin , and it is related to the response to a perceived stress (loss or 305 R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena past trauma, stress a sensitizer for the future). These individuals are more imp ulsive and often commit more suicide attempts (but with lower mortality), tendin g to seek help. This type is more common in women, who tend to self-medicate wit h anxiolytic drugs such as benzodiazepines, marijuana, alcohol and, most commonl y, excessive eating (bulimic behavior and / or weight gain). Some of these patie nts exhibit transformation to bipolar disorder type II9. The second type of dyst hymia proposed is the "anergic dysthymia, characterized by low energy, low react ivity, and anhedonia. This psychomotor inertia is etiologically related to lower levels of dopamine. These patients are more often male, have less interest in s ex, are less impulsive, have hypersomnia and decreased REM sleep and tend not to seek help. A portion of these patients tend to self-medication with stimulant d rugs of abuse such as methamphetamine, cocaine, nicotine and caffeine. Some pati ents exhibit transformation to bipolar disorder type I9. Within this hypothesis, the biological mechanisms involved in these two distinct types of dysthymia may respond differently to different types of antidepressants. Thus, Niculescu III & Akiskal proposed that anxious dysthymia, related to low serotonin levels, resp ond better to specific reuptake inhibitors (SSRI). Already anergic dysthymia, re lated to low levels of dopamine, is more responsive to dopaminergic and noradren ergic medications such as bupropion, venlafaxine, stimulants and antidepressants tricíclicos9. Comorbidity with Major Depressive Disorder The term comorbidity h as been used by Feinstein (1970) to mean "any distinct additional clinical entit y that exists or may occur during the clinical course of a disease '25. Despite the different classes of existing comorbidities, we will use the class "medical comorbidity,€As regards the difference in course and response to treatment of a disorder. The importance of identifying a clinical comorbidity in dysthymic diso rder is, among other things, the possibility of predicting the prognosis and the need to establish strategies 306 differentiated treatment for each condition mórbidas25. The TDM is the most comm on psychiatric disorder that is associated with distimia25 and confirmed that it increases the risk of a depressive episode maior5, 14,15,19,20,40,45,53. Most d ysthymic patients will develop at some point in life, episodes of MDD 14,15,45,5 3, and some studies show that almost all the terão2, 19.20. An estimated further that 40% of patients with episodes of MDD also meet the criteria for dysthymic disorder 5.7. The concomitance of these two diseases is called "double depressio n" (DD) 19,20,25,54. Stressful life events are important triggers of DD in patie nts distímicos53. Patients with DD have more severe depressive symptoms 45.55, m ore chronic course and more comorbidities compared with patients with MDD or dys thymia pure 55 pure 45. The level of functional disability in these patients is higher than in patients with both pathologies isoladas20 as well as the rate of hospitalization and recurrence of TDM54 50. The rate of comorbidity with anxiety disorders, substance abuse, personalidade54 disorders and irritable bowel syndr ome 25 is also higher in DD compared with major depression alone. The rate of re covery from an episode of MDD is lower in patients with DD than in those with si

ngle episode of MDD 14.18, and when recovery occurs, in most cases is not comple ta18. The prognosis is worse, and treatment should be directed to both transtorn os7. Pepper et al.45 found a recurrence rate for MDD significantly higher in pat ients with DD (82.1%) than in patients with single episode of MDD (62.2%) 45. Mo st dysthymic had a history or current DD, and the patients with DD had a poor le vel of functioning that dysthymic puros45. Tucci et al.50 studied levels of soci al adjustment in various subcategories of affective disorders (bipolar, unipolar , dysthymia and DD) 50. Patients with DD, along with bipolar, presented the wors t levels of social adjustment. Patients with DD had also the worst record in fam ily relations. Stressful events were related to the onset and recurrence of all categories of affective disorders. The emotional quality of R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena family environment was considered as predictive of the course afetivos50 disorde rs. A diagnostic system can influence the degree of comorbidity found. The more classes a diagnostic system has, the greater the possibility that a patient rece ives more than one diagnosis. Comorbidity may just reflect the excessive subdivi sion 25. In this regard, the discussion categorical versus dimensional becomes e ssential especially in the distinction between dysthymia and MDD. As noted earli er, recent research on dysthymia emphasize its connection with other forms of su bsyndromal and full disease (MDD), suggesting that, within a dimension or depres sive spectrum, these different forms may only reflect different degrees of the s ame disease continuum, ie differences quantitative rather than qualitative 15,16 ,19,36,44,45,56. Despite doubts about the various subtypes of depression are suf ficiently distintos16, 57, the DD remains an accepted diagnosis. Keller et al. r eviewed the distinctions between dysthymia, episodes of MDD and DD, DD hypothesi zing as a subtype of unipolar depression. The authors concluded that it is not p ossible to define DD as a subtype of major depression, suggesting that a separat e classification of DD and MDD is still justificada54. Goodman et al. 58 studied discriminating factors (and their consequences) in children and adolescents wit h MDD and dysthymia. The findings did not support strong discriminant between MD D and dysthymia in this sample, but suggested that the combination of the two le ads to more disability and lower social competence, and higher propensity to anx iety. Thus, children with DD are more likely to be seriously compromised in seve ral areas of functioning, to have more symptoms and greater impairment in social and familiar58. compared Flament et al. 38 Phenomenology, psychosocial correlat es and seeking treatment in adolescents with an episode of MDD with dysthymia an d controls.€Patterns of affective symptoms were similar in patients with dysthym ic and MDD episodes, and the latter had more comorbid conditions. And dysthymic patients with MDD also sought some treatment settings for your conditions. The a uthors highlight the severity of both condições38. Klein et al. 49 disorders ass essed mood and personality in 1st degree relatives of dysthymic patients with MDD and controls. The results showed that there is a strong familial relationship betwee n dysthymia and MDD. However, dysthymia is also slightly different because it is specifically aggregate in relatives of patients with dysthymia. Lastly, dysthym ia and MDD present themselves as having a family association with personality di sorder, although this connection is somewhat stronger for distimia49. Kovacs et al.57 in a prospective naturalistic study of 12 years of follow up, compared cha racteristics of childhood-onset dysthymia and MDD with first episode also in chi ldhood. The dysthymia was associated with younger age at which the TDM, as well as greater overall risk for any subsequent affective disorder, particularly MDD and bipolar57 disorder. Riso et al. 23 reviewed six factors implicated as determ inants of chronic depression (dysthymia well as chronic major depression). The a uthors found no qualitative differences between acute and chronic forms of depre ssion. Developmental factors (childhood adversity) were the most important findi

ngs related to chronicity of depression. Thus, the development of chronic depres sion involves increased levels of childhood adversity, protracted stress environ ments and increased reactivity to estresse23. In simple comparison with episodic MDD, dysthymia appears to be an entity of greater severity. Klein et al. In a p rospective naturalistic study of 5 years of follow-up, described some results on the course of the disorder distímico19. The estimated recovery of dysthymic dis order at 5 years was 53.9%. Among those who recovered, the estimated risk of rel apse was 45.2%. Patients with dysthymia were approximately 70% of follow-up meet ing all the criteria for a mood disorder. During the course of follow-up, patien ts with dysthymia exhibited significantly higher levels of symptoms and lower fu nctioning and were significantly more likely to attempt suicide and be hospitali zed than patients with episodic MDD. The risk estimate for the first episode of MDD in dysthymic patients at 5 years was 76.9%. The authors conclude that dysthy mia is a chronic condition with a prolonged course and a high relapse rate. Almo st all patients with dysthymia 307 R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena eventually develop MDD superimposed. Although patients with dysthymic disorder t end to produce mild to moderate symptoms in a longitudinal perspective is the co ndition severa19. DISCUSSION Much of modern thinking about mood disorders dates back to the old concepts gregos8. These concepts have evolved over several centu ries and form the fundamental basis for the evolution of psychiatry. However, th ey were postulated random. As pointed out by Lopes 59, the concepts of nosologic al entities that were consolidated itself (more solidly with Kraepelin, Freud an d Schneider, among others) were not established arbitrarily. They are all produc ts of an accumulation of observations, reflections and relationships with patien ts. Currently, many articles incorporate these works, which, particularly with K raepelin, were fundamental to the current concept of dysthymia. Kraepelin's idea of a continuum model within a spectrum of depressive disorders is now a major f ocus of study of contemporary authors, showing how important may be the historic al contributions in the evolution of psychiatry. The historical and nosological study of dysthymia was fundamental practical importance in clinical developments that entity. Once considered a personality disorder, with a range of therapeuti c limitations, today dysthymia is classified as a mood disorder, which extended its therapeutic and altered their prognosis. Moreover, this evolution has also e xtended the findings about their clinical and paved the way for promising theori es about its etiology, contributing also to better understand the spectrum of mo od disorders. Despite the high morbidity and even the 80 had little researched a lternative treatment of dysthymia: it was considered a personality disorder unre sponsive to treatment antidepressivo7.€Today there seems no doubt that her inclu sion among the mood disorders represent a major advance in the treatment of pati ents chronically deprimidos60. They now approached within a therapeutic perspect ive of affective disorders, resulting in an increase interest in pharmacological treatment 40.60. Studies show that 50-60% of patient s with dysthymia respond to treatment with antidepressants 61.62. The monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and SSRIs are effec tive in the treatment of dysthymia 40,61,63,64. Manipulations and hormone replac ement studies are needed of 65.66. The treatment of currently accepted and consi dered more effective is the combination of pharmacotherapy with psychotherapy, e specially cognitive and behavioral 6,7,40. The many studies that have been made about the lack dysthymia, however, greater methodological standardization. Almos t all clinical studies reviewed in this article reported methodological limitati ons that make it difficult to generalize the results. These limitations, and pec uliarities of each study may be attributed to the current difficulty of adopting

a standard concept of dysthymic disorder. Even the official classifications (IC D-10 and DSM-IV) have different diagnostic criteria. Moreover, these differences are not that many results to be repeated and give, and gradually the "new face" of dysthymia. More detailed studies, with concepts and standardized criteria ar e necessary for this disorder, so prevalent and costly, is better understood and better treated. CONCLUSION dysthymic disorder is an important cause of morbidit y, very prevalent in our environment and increasing the financial costs and the use of the health system. The concept of dysthymia, originally broad and unspeci fic, has undergone many changes over time and is now included among the mood dis orders, the spectrum of chronic depressions. This new nosological classification represented a major step towards a better understanding of the entity, and to a pharmacological approach in its treatment. The relationship between dysthymia a nd other mood disorders, particularly MDD, is now the subject of many studies an d controversies. Current studies are still methodologically limited, the result also of the lack of standardization in the description of the disorder. Given it s importance, further studies with careful methodology and substantial samples s hould be 308 R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena encouraged so we can better understand and treat this disorder. REFERENCES 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, Fra nces A, Freeman HL, Keller MB, Lapierre YD, et al. Dysthymia in clinical practic e. Br J Psychiatry 1995; 166:174-83. 3. Griffiths J, Ravindran AV, Merali Z, Ani sman H. Dysthymia: a review of pharmacological and behavioral factors. Mol Psych iatry 2000; 5:242-61. 4. Serretto A, Jori MC, Casadei L, Ravizza L, Smeraldi E, Akiskal H. Delineating psychopathologic clusters Within dysthymia: a study of 51 2 Out-Patients without major depression. J Affect Disord 1999, 56:17-25. 5. Akis kal HS. Dysthymia: clinical and external Validity. Acta Psychiatr Scand 1994; 89 (suppl 383) :19-23. 6. Nardi AE. Epidemiological study in dysthymia. J Bras Med 1999; 77 (1) :85-96. 7. Kaplan HI, Sadock BJ, GREBB JA. Compendium of psychiatr y. 7th ed. Porto Alegre: Artes Médicas, 1997. 8. Akiskal HS. Mood disorders. In: Sadock BJ, Sadock VA, eds. Kaplan & Sadock's Comprehensive Textbook of Psychiat ry. 7th ed. Philadelphia: Library of Congress, 1999. vol. 1. 9. Niculescu III AB , Akiskal HS. Proposed endophenotypes of dysthymia: evolutionary, clinical and p harmacogenomic considerations. Mol Psychiatry 2001; 6:363-6. 10. In RM. Is depre ssion 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 Di fferences in chronic major and double depression. J Affect Disord 2000, 60:1-11. 13. Niculescu AB, Akiskal HS. Fri hormones, Darwinism, and depression. Arch Gen Psychiatry 2001; 58 (1) :1083-4. 14. Keller MB. Course, outcome and impact on t he community. Acta Psychiatr Scand 1994; 89 (suppl 383): 2434. 15. Avrich BS, El kis H. Prevalence and underrecognition of dysthymia among psychiatric outpatient s in Sao Paulo, Brazil. J Affect Disord 2002; 69:193-9. 16. Akiskal HS. Dysthymi a as a temperamental variant of affective disorder. Eur Psychiatr 1996; 11 (supp l 3): 117s22s. 17. Katon W, Russo J, Frank E, Barrett J, Williams JW, Oxman T, e t al.€Predictors of nonresponse to treatment in primary care patients suffering from dysthymia. Gen Hosp Psychiatry 2002; 24:20-7. 18. Nardi AE, Saboya E, Pinto S, Figueira I, Marques C, Mendlowicz M, et al. Dysthymia: clinicotherapeutic as pects. J Bras Psiq 1993, 42 (7) :357-72. 19. Klein DN, Schwartz JE, Rose S, Lead er 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. Outco me of dysthymic disorder at 5-year follow-up: the effect of familial psychopatho logy, early adversity, personality, comorbidity, and chronic stress. Am J Psychi

atry 2001; 158:1864-70. 21. Lizardi H, Klein DN. Parental psychopathology and re ports of the childhood home environment in adults with early-onset dysthymic disorder. J Nerv Ment Dis 2000, 188 (2) :63-70. 22. Gilmer WAS, 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. Th e search for determinants of chronic depression: a review of six factors. J Affe ct Disord 2000; 70:103-15. 24. Westermeyer J, Eames SL, Nugent S. Comorbid dysth ymia and Substance disorder: treatment history and cost. Am J Psychiatry 1998; 1 55 (11) :1556-60. 25. Moreno RA, Moreno DH. The relationship between other psych iatric and dysthymia. In: TA Cordás, Nardi AE, Moreno RA, Castel S, eds. Dysthym ia - a bad mood evil mood. Porto Alegre: Artes Médicas, 1997. p.42-52. 26. Freem an HL. Historical and nosological Aspects of dysthymia. Acta Psychiatr Scand 199 4; 89 (suppl 383): 711. 27. Cordás TA. Depression: the neurotransmitters of the black bile - a historical introduction. São Paulo: Lemos; 2002. 28. Cordás TA. T he grumpy mood evil - a historical perspective. In: TA Cordás, Nardi AE, Moreno RA, Castel S, eds. Dysthymia - a bad mood evil mood. Porto Alegre: Artes Médicas , 1997. p.15-21. 29. Cordás TA, A. Taveira Oxcarbazepine in bipolar disorder. Sã o Paulo: Lemos; 2003. 30. Alcantara R, Schmitt R, Schwarzthaupt AW, Chachamovich And Sulzbach MFV, Padilha RTL, et al. Advances in the diagnosis of bipolar diso rder. Rev Psiquiatr RS 2003; 25 (suppl 1) :22-32. 31. Nardi AE, Cordás TA. Dysth ymia and personality. In: TA Cordás, Nardi AE, Moreno RA, Castel S, eds. Dysthym ia - a bad mood evil mood. 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 3 83) :12-8. 33. Kwon JS, Kim YM, Chang CG, Park BJ, Kim L, Yoon DJ, et al. Threeyear follow-up of women with the sole diagnosis of depressive personality disord er: Subsequent development of dysthymia and major depression. Am J Psychiatry 20 00; 157 (12) :1966-72. 34. Castel S, Scalco MZ. Dysthymia: clinical picture and diagnosis. In: TA Cordás, Nardi AE, Moreno RA, Castel S, eds. Dysthymia - a bad mood evil mood. Porto Alegre: Artes Médicas, 1997. p.23-41. 35. Anderson RL, Kle in 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 dep ressive spectrum: diagnostic classification and course. J Affect Disord 1997, 45 :31-40. 37. Klein DN. Depressive personality in the relatives of outpatients wit h 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 200 1, 40 (9) :1070-8. 39. Akiskal HS, Judd LL, Gillin C, Lemmi H. Subthreshold depr essions: clinical and polysonographic validation of dysthymic, residual and mask ed forms. J Affect Disord 1997, 45:53-63. 40. Brunello N, Akiskal H, Boyer P, Ge ssa GL, Howland RH, Langer SZ, et al. Dysthymia: clinical picture, extent of 309 R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena overlap with chronic fatigue syndrome, neuropharmacological considerations, and new therapeutic vistas. J Affect Disord 1999; 52:275-90. 41. Akiskal, HS. Valida ting 'hard' and 'soft' phenotypes Within the Bipolar spectrum: continuity or dis continuity? J Affect Disord 2003; 73:1-5. 42. Angst J, Gamma A, Benazzi F, Ajdac ic V, Eich D, Rössler W. Toward a re-definition of subthreshold bipolarity: epid emiology and Proposed Criteria for bipolar-II, minor bipolar disorders and hypom ania. J Affect Disord 2003; 73:133-46. 43. Angst J. Dysthymia and personality. E ur Psychiatry 1998; 13:188-97. 44. Barzega G, Maina G, Venturelli S, Bogetto F. Dysthymic disorder: clinical Characteristics in relation to age at onset. J Affe

ct Disord 2001, 66:39-46. 45. Pepper CM, Klein DN,€Anderson RL, Riso LP, Ouimett e PC, Lizardi H. DSM-III-R axis II comorbidity in dysthymia and major depression . Am J Psychiatry 1995; 152:23947. 46. Garfallos G Adamopoulou A Karastergiou A Voikli M, Sotiropoulos A, Donias S, et al. Personality disorders in dysthymia an d major depression. Acta Psychiatr Scand 1999; 99 (5) :332-40. 47. Bellino S, Pa tria L, Ziero S, Rocca G, Bogetto F. Clinical features of dysthymia and age: a C linical 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-on set dysthymic disorder: comparison in out-patients with superimposed major depre ssive episodes. J Affect Disord 1999; 52:187-96. 49. Klein DN, Riso LP, Donaldso n SK, Schwartz JE, Anderson RL, Ouimette PC, et al. Family study of earlyonset d ysthymia. Arch Gen Psychiatry 1995; 52:487-96. 50. Tucci AM, Kerr-Corrêa F, Dalb en I. Social adjustment in patients with bipolar affective disorder, unipolar, d ysthymia and double depression. J Affect Disord 2001, 23 (2) :79-87. 51. Devanan d DP, Adorno E, Cheng J, Burt T, Pelton GH, Roose SP, et al. Late onset dysthymi c disorder and major depression Differ from early onset dysthymic and major depr ession in elderly outpatients. J Affect Disord. (In press.) 52. Migliorelli R, T esóm A, Sabe L, M Patracchi, Leiguarda R, Starkstein SE. Prevalence and correlat es of dysthymia and major depression among patients suffering from Alzheimer's d isease. 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 Disor d 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, Jensen P. Major depression and dysthymia and adolescent s: discriminant Validity and Consequences in a community sample. Am J Adolesc Ps ychiatry 2000, 39 (6) :761-70. Shaffer D, in children differential Acad Child Adolesc Psychiatry 2000, 39 (6) :761-70. 59. Lim CB. Current ethical challenges in psychiatry. Bioethics 2001; 9 (1) :29-43. 60. Lima MS. Pharmacotherapy of dys thymia: critical evaluation of scientific evidence. J Affect Disord 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 pharm acotherapy: clinical and functional impairments SYMPTOMS. Am J Psychiatry 1999; 156 (10) :1608-17. 62. Williams JW, Barrett J, Oxman T, Frank E, Katon W, Sulliv an M, et al. Treatment of dysthymia and minor depression in primary care: a rand omized controlled trial in older adults. JAMA 2000; 284 (12) :1519-26. 63. Akisk al H. Dysthymic disorder - Interview with 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 de pression and dysthymia with high-dose thyroxine. Biol Psychiatry 1999; 45:22933. 66. DN Seidman, 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. ABSTRACT dysthymic disorder is a chronic and disabling depression, occurring in a substantial portion of the population (3-6%) and increasing risks of major dep ressive disorder. It is associated with considerable disability and high comorbi dity. The nosological status of dysthymia has aroused considerable controversy o ver the past decades, and some investigations to consider as a mood disorder, an d others as a personality disorder. Ranked among nosography current mood disorde rs, dysthymia is now a treatable entity and needs to receive greater attention b ecause of its morbidity. This article reviews the main historical aspects of dys thymia, nosological characteristics, subtypes and their relationship with major depressive disorder. Finally, we conclude that further studies are needed to val idate the concept of dysthymia and the spectrum of chronic depressions, for bett er understanding the etiology and therapy based on evidence. Keywords: Dysthymia, depression, mood disorders, comorbidity, historical and nos ological aspects.

56. Klein DN, Kocsis JH, McCullough JP, Holzer CE III, Hirschfeld RMA, Keller MB . Symptomatology in major depressive and dysthymic disorder. Psychiatr Clin N Am 1996; 19 (1) :41-53. 57. Kovacs M, Akiskal HS, Gatsonis C, Parron 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: differential discriminant Validity and Consequences i n a community sample. J Am Acad Child ABSTRACT Dysthymia is a chronic and incapacitating form of depression That Affec ts a Substantial Portion of the population (3-6%) and Increase The major risk fo r depressive disorder. It is Associated with Significant Disabilities and high c omorbidity. The nosological 310 R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004 Dysthymia and major depressive disorder - Spanemberg & Juruena status of dysthymia Has Been Associated with considerable controversy over the p ast decades: some investigators Regard it as a mood disorder, and others as a pe rsonality disorder. Currently Classified among the mood disorders, dysthymia is a treatable disorder and now Should receive more attention in view of ITS Associ ated morbidity. The present article reviews the main historic Aspects of dysthym ia, ITS nosological features and Its relationship with major depressive disorder . We conclude That Further studies are Necessary in order to validate the concep t of dysthymia and the spectrum of chronic diseases, in order to Provide a bette r understanding of the disorder as well as evidence-based guidelines. Keywords: Dysthymia, depression, mood disorders, comorbidity, historical and nos ological aspects. Title: Dysthymia: historical / nosological Characteristics and Its relationship with major depressive disorder decades pasadas, siendo algunas Investigations that consideraron as siendo la un trastorno del humor y otras como un trastorno de personalidad. La la clasifica nosography current between them trastornos del humor, siendo hoy y una Entidad t ratable Just Need the cause of bad atención de su morbilidad. Este artículo los principales reviews historical aspects of her dysthymia, sus characteristics nos ological subtypes y su relación con el trastorno Depresivo mayor. Al final, we c onclude that If you get stuck to validate nuevos estudios el concepto y el of dy sthymia spectrum of chronic depresion for una mejor comprensión y for etiologica l con base en una terapéutica evidence. Palabras clave: Dysthymia, depresión, trastornos del cheer, comorbilidad, y noso logical historical aspects. Title: Dysthymia: historical features nosological y y su relación con el trastorno Depresivo mayor Correspondence: Lucas Spanemberg Rua José do Patrocinio, 382/82 - CEP 90050-000 Cidade Baixa - Porto Alegre - RS Fone: (51) 3224.7365 / 9175.6131 Email: Copyright © lspanemberg@yahoo.com.br Rev ista de Psiquiatria do Rio Grande do Sul - SPRS RESUMEN El trastorno es una dysthymic chronic and disabling form of depresión, w hich ocurre en una población de la significant portion (3-6%) y los riesgos incr eases of trastorno Depresivo mayor. You incapacitaciones considerables y asociad o a high comorbilidad. El nosological status of dysthymia viene la provoking con troversy muchas a lo Largo de las 311 R. Psiquiatr. RS, 26 '(3): 300-311, Sep. / Dec. 2004

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