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Clinical differences between melancholic and nonmelancholic depression as defined by the CORE system
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Comprehensive Psychiatry 54 (2013) 11 – 15 www.elsevier.com/locate/comppsych
Clinical differences between melancholic and nonmelancholic depression as defined by the CORE system Marco Antonio Knob Caldieraro a,⁎, Fernanda Lucia Capitanio Baeza a , Diesa Oliveira Pinheiro a , Mariana Rangel Ribeiro a , Gordon Parker b , Marcelo P. Fleck a a
Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-003, Brazil b Black Dog Institute, Prince of Wales Hospital, Randwick, NSW 2031, Australia
Abstract Background: The definition and delineation of melancholia have remained elusive for an extended period. A longstanding signal of psychomotor disturbance has been operationalized via the observer-rated CORE measure and with CORE-assigned melancholic and nonmelancholic compared in several Australian studies. Replication studies in other regions have not previously been reported. This study compares Brazilian patients with melancholic and nonmelancholic depression according to the CORE measure of psychomotor disturbance in terms of clinical characteristics, suicide ideation, stressful life events, quality of life, parental care, and personality styles. Methods: A total of 181 patients with unipolar major depression attending a tertiary care outpatient service in Brazil were evaluated in relation to melancholic status and study variables. Results: The CORE-assigned melancholic patients presented higher symptom severity, greater prevalence of suicide ideation, and Axis I comorbidities than nonmelancholics. Scores of dysfunctional personality styles and dysfunctional parental care measures were also higher among melancholics. Quality-of-life scores were low in both groups. Limitations: The absence of a criterion standard for the diagnosis of melancholia and the use of medication can be potential limitations of the study. Conclusion: Differences suggest that CORE-assigned melancholia defines a distinct group of patients and probably a disorder distinct from nonmelancholic depression not only in quantitative but also in qualitative aspects. © 2013 Elsevier Inc. All rights reserved.
1. Introduction Most of the discussion about the concept of melancholia is linked to the debate as to whether depression should be classified as a unitary or binary disorder [1,2]. By the time that Diagnostic and Statistical Manual of Mental Disorders (DSM), Third Edition, was published, there was not enough empirical support for the binary model, so the manual favored a dimensional model. Nevertheless, a specifier for major depression with melancholia was included, keeping the question about the status of melancholia open [3]. The DSM Fourth Edition (DSM-IV) model is similar to that of DSM Third Edition. However, the melancholic specifier of ⁎ Corresponding author. Rua Ramiro Barcellos, 2350. 4º andar, Serviço de Psiquiatria, 90035-003 Porto Alegre, Rio Grande do Sul, Brazil. Tel.: +55 51 3359 8264; fax: +55 51 3359 8264. E-mail address: [email protected] (M.A.K. Caldieraro). 0010-440X/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.comppsych.2012.05.012
DSM-IV is not broadly used, probably because its assignments differ little from the overall major depression [4]. Many features have been used to define melancholia [5,6]. Parker et al [7] judged that observable psychomotor disturbance (PMD) was one of the most longstanding clinical markers of melancholic depression. They developed the CORE measure to operationalize the assessment of PMD. This instrument was validated by comparison with clinical and neuroendocrine measures [6,8]. The discrimination of melancholic depression according to PMD is part of a larger model for classifying depression across 3 subtypes (nonmelancholic, melancholic, and psychotic) [9]. Studies independent of the Australian group have not been published, inviting the current study. Depressive subtypes have been shown to differ across several variables, including psychiatric comorbidities [10], personality [11,12], parental care [12,13], stressful life events [14,15], and quality of life (QOL) [16,17]. The aim
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M.A.K. Caldieraro et al. / Comprehensive Psychiatry 54 (2013) 11–15
of this study is to evaluate if patients with melancholic depression, according to the CORE measure, differentiated from nonmelancholic subjects on clinical characteristics described above and in terms of symptoms severity, suicide ideation, and other clinical features.
2. Materials and methods 2.1. Subjects All outpatients (n = 232) referred to the Mood Disorders Program of the Hospital de Clínicas de Porto Alegre during the study period were enrolled. The outpatient tertiary care service focuses on managing unipolar depressive disorders in adults. Patients experiencing a major depressive episode were included. Exclusion criteria were a previous history of mania or hypomania or inability to understand the research instruments. The investigation was approved by the medical ethics committee of the Hospital de Clínicas de Porto Alegre, and all participants provided written, informed consent. 2.2. Measures Major depression, current and past episodes, and psychiatric comorbidities were diagnosed according to the Mini International Neuropsychiatric Interview, Brazilian version [18]. Severity of depression was assessed by the Hamilton Depression Rating Scale (HAM-D) [19] and the Beck Depression Inventory (BDI) [20]. Assignment to melancholic and nonmelancholic groups was undertaken by the CORE measure. A CORE score greater than or equal to 8 held to indicate likely melancholia [6] and was adopted in this study. The presence of suicidal ideation was determined by taking into account the BDI suicide item. The rating of “I don't have any thoughts of killing myself” was considered as no suicide ideation. The other statements were considered as indicative of suicide ideation. The presence of life event stressors during the 12 months before the starting of the current episode was assessed by a self-reported inventory, used by Parker et al [21] in a previous study. Quality of life was assessed by the World Health Organization's Quality of Life Instrument short version, Brazilian version [22,23]. Parental care was assessed by the Measure of Parental Style (MOPS) [24]. The Temperament and Personality (T&P) questionnaire was used to study personality styles. This instrument seeks to quantify personality constructs providing risk to depression [25]. We performed a translation and cultural adaptation of the CORE, MOPS, and T&P instruments following the guideline from the Translation and Cultural Adaptation group of the International Society for Pharmacoeconomics and Outcomes Research [26]. This process was described elsewhere using MOPS as example [27].
2.3. Statistical analysis Data were analyzed with the SPSS version 16.0 (SPSS, Inc, Chicago, IL). Continuous data were compared by Student t test for normally distributed data and by the Mann-Whitney U test for data with nonnormal distributions. Categorical variables were compared by the χ 2 test; in cases with the expected frequency less than 5 in more than 20% of categories, Fisher exact test was used. All tests were 2 tailed, and P b .05 was used as the criterion for statistical significance.
3. Results From the 232 patients evaluated, 181 were included for analysis. Reasons for exclusion were patient not presenting a current major depression episode (n = 17), history of mania or hypomania (n = 24), and patient unable to understand the research instruments (n = 1). Forty-five patients (24.9%) met the 8-or-more CORE cutoff criterion score, with the remaining 136 patients (75.1%) assigned as having nonmelancholic depression. There were no differences in sociodemographic variables between groups (Table 1). Severity of depression was different between groups when assessed by the HAM-D. The score on this scale was higher in the melancholic patients (difference of means, 4.45; 95% confidence interval [CI], 2.76-6.14). The effect size for this difference was 0.84. Scores on the BDI, a self-rated scale, were also higher in the melancholic group, but this difference did not achieve statistical significance. Table 1 Demographic characteristic
Age, mean (SD) Sex, n (%) Female Ethnicity, n (%) White African American Other Marital status, n (%) Married Never Married Divorced Widowed Education, n (%) Nonalphabetized Primary school High school College Employment status, n (%) Employed Unemployed Retired Disablement benefit Unwaged domestic work Other
Nonmelancholic (n = 136)
Melancholic (n = 45)
P
49.60 (11.4)
46.13 (12.1)
.084 .279
123 (90.4)
38 (84.4)
109 (80.1) 16 (11.8) 11 (8.1)
34 (75.6) 6 (13.3) 5 (11.1)
75 (55.1) 26 (19.1) 16 (11.8) 19 (14.0)
26 (57.8) 11 (24.4) 6 (13.3) 2 (4.4)
8 (5.9) 66 (48.5) 54 (39.7) 8 (5.9)
2 (4.4) 25 (55.6) 14 (31.1) 4 (8.9)
26 (19.1) 28 (20.6) 28 (20.6) 31 (22.8) 10 (7.4) 13 (9.6)
10 (22.2) 12 (26.7) 3 (6.7) 8 (17.8) 6 (13.3) 6 (13.3)
.776
.358
.668
.241
M.A.K. Caldieraro et al. / Comprehensive Psychiatry 54 (2013) 11–15
The correlation of these 2 measures was moderate (r = 0.44, P b .001). Clinical differences between groups are described in Table 2. Suicide ideation was more prevalent in melancholic depression. The prevalence ratio (PR) was 1.43 (95% CI, 1.17-1.75). Although not formally statistically significant, the melancholic patients had a higher prevalence of past major depression episode, medical comorbidity, family history of depression, and psychiatric disorder. The prevalence of serious life event stressor exceeded 85% in both groups, with no significant differences (P = .66). The presence of any Axis I psychiatric comorbidity was high in both groups but significantly higher in melancholic depression (PR, 1.19; 95% CI, 1.06-1.33). When comorbidities were analyzed individually, statistically significant difference was found only for social phobia, which was higher in melancholic depression (PR, 1.78; 95% CI, 1.212.63). Other anxiety disorders also showed a tendency to be more prevalent in melancholia. Both groups showed low QOL scores. Despite not achieving statistical significance, all scores were lower in melancholic depression. Scores for each domain were, respectively, for melancholics and nonmelancholics: physical health, 30.93 vs 31.14 (P = .94); psychological, 29.73 vs 32.14 (P = .40); social relationships, 43.56 vs 46.69 (P = .42); environment, 40.86 vs 43.88 (P = .25); and global QOL, 33.81 vs 34.74 (P = .76).
Table 2 Clinical characteristics
HAM-D, mean (SD) BDI, mean (SD) Suicidal ideation Past MDE, n (%) Psychiatric comorbidities, n (%) Presence of any comorbidity Social phobia Panic disorder Agoraphobia without panic OCD PTSD Alcohol dependence Substance dependence Anorexia Bulimia GAD Medical comorbidity, n (%) FH psychiatric disorder, n (%) FH depression, n (%) Life event stressor, a n (%)
Nonmelancholic (n = 136)
Melancholic (n = 45)
P
18.7 (4.8) 32.4 (10.9) 77 (57.5) 77 (56.6)
23.1 (5.5) 35.3 (9.6) 37 (82.2) 20 (46.5)
b.001 .124 .003 .246
107 (78.7) 39 (28.7) 12 (10.9) 28 (20.6) 23 (16.9) 13 (9.6) 3 (2.2) 7 (5.1) 0 (0.0) 2 (1.5) 69 (50.7) 115 (84.6) 109 (82.6) 96 (72.7) 111 (86.0)
42(93.3) 23 (51.1) 9 (20.0) 15 (33.3) 10 (22.2) 6 (13.3) 1 (2.2) 0 (0.0) 0 (0.0) 1 (2.2) 29 (64.4) 39 (86.7) 36 (80.0) 32 (71.1) 39 (88.6)
.025 .006 .090 .082 .424 .574 1.000 .195 1.000 .110 .731 .698 .834 .662
Substance dependence is dependence of a substance other than alcohol. MDE indicates major depressive episode; OCD, obsessive-compulsive disorder; PTSD, posttraumatic stress disorder; GAD, generalized anxiety disorder; FH, family history. a Presence of at least 1 life event classified by the patient as severe, extreme, or catastrophic in the 12 months before the starting of the current depressive episode.
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Maternal abuse, assessed by the MOPS, were higher among melancholics (median, 5.0 vs 2.0; P = .026). There were no differences in the subscales of maternal indifference and overcontrol. There were no differences in scores for paternal care. Regarding personality dysfunction as assessed by the T&P measure of personality styles, those with melancholic depression presented higher scores on personal reserve (17.36 vs 14.30, P = .005) and social avoidance (16.33 vs 14.27, P = .012). There were no statistically significant differences on the 6 other constructs.
4. Discussion Depression severity was greater in melancholic patients when assessed by the HAM-D. The difference was large as reflected by the effect size. This finding demonstrates the capacity of the CORE measure to discriminate 2 groups of depression according to the severity of symptoms in a clinician-rated scale. It also supports the model proposed by Parker et al, which suggests a gradient of symptom severity lower in nonmelancholic, intermediate in melancholic, and higher in psychotic depression [7]. However, when severity of depression was assessed by the BDI, a self-rated scale, no difference was found between the groups. The moderate correlation found between HAM-D and BDI in this sample is consistent with most studies [28]. Patients with moderate to severe depression and those with the nonmelancholic subtype tend to score higher in self-report ratings [29]. These observations could explain the lack of difference in BDI scores. The finding that patients with melancholic depression, as assigned by CORE, had a greater prevalence of suicide ideation is relevant. Suicide is a major problem in psychiatry, and depression is the nosological entity most associated with suicidal behavior [30], but predicting which depressive patients will attempt suicide is a difficult task. A study using DSM criteria for melancholia found an association of this subtype with more serious past suicide attempt and the probability of future attempts [31]. However, studies using DSM or Research Diagnostic Criteria (RDC) constructs of melancholia are inconclusive about the association of melancholia and suicide [32]. Although measuring only suicide ideation, the present study suggests that patients with CORE-defined melancholia are a distinct group with increased suicide risk. Classical descriptions associate melancholia with genetic determinants, suggesting a higher prevalence of family history of depression in this subtype. In our sample, the prevalence was similar across the melancholic and nonmelancholic groups. Although diverging from the classical descriptions, this result is similar to most empirical studies [33]. Melancholia is also classically described as not being associated distinctly with stressful life events. In this study, melancholic patients presented a high prevalence of such
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events and similar to the nonmelancholic group. This result also diverges from classical description but agrees with most empirical studies [32]. The higher prevalence of Axis I comorbidity in the melancholic group was underpinned by anxiety. Although a significant difference was found only for social phobia, a tendency for higher rates of panic disorder and agoraphobia was found among the melancholic patients. Interestingly, the personality styles higher in the melancholic subgroups were personal reserve and social avoidance, traits related to social phobia. It could be that personality traits associated with less social interaction predispose to both social phobia and to melancholia. Another possibility is that social withdrawal is a manifestation of melancholia with symptoms intense enough to produce a clinical diagnosis of social phobia. The high social anxiety traits may be a characteristic of Brazilian population, as opposing results were found in an Italian study using the same instruments [34]. An Australian study found a higher prevalence of avoidant personality disorder in nonmelancholics [35]. Another study found a higher prevalence of avoidant personality disorder in melancholics and no difference in social phobia [8]. Higher maternal abuse among the melancholic patients suggests that it might lead to melancholic depression. However, this result should be considered carefully because it is divergent from other studies [24,36]. Both groups presented low QOL scores in all domains without differences between melancholic and nonmelancholic depression, suggesting that the impact of depression on QOL is intense but not related to the depressive subtype. This is the first study to compare QOL in nonmelancholic and melancholic depression assigned by the CORE measure, although 1 study found similar results using the DSM-IV criteria of melancholia [37]. A limitation of this study is that it was conducted in a tertiary care facility where most patients had already been medicated before referral. Thus, they could have achieved some improvement of the PMD by the time of the interview. Another limitation is that there is no criterion standard for the diagnosis of melancholia. The CORE measure is subjected to variability and presents no absolute sensibility and specificity [6]. Despite these limitations, we found that melancholic depression as defined by the CORE measure differentiated from the nonmelancholic subtype in severity of symptoms, suicide ideation, Axis I comorbidities, personality styles, and parental care. Such differences reinforce melancholia as a distinct disorder. They also remark the importance of PMD in the diagnosis of melancholia and contribute to validate the CORE for assessment of PMD. As a future perspective, the discrimination of distinct depressive subtypes will be of greater value if it helps to identify specific treatments for each subtype. Some studies compared the response to pharmacologic treatment in melancholic and nonmelancholic depression according to
CORE. Most of them were carried out in Australia by Parker et al [38,39]. Results suggest that melancholics present a better response to tricyclic antidepressants than to selective serotonin reuptake inhibitors, whereas response was similar to both classes of drugs among nonmelancholics. Interestingly, this difference seems to be increased in older patients [39]. A study independent of the Australian group found an unexpected better response to fluoxetine compared with nortriptyline in severe melancholia [8]. Our group is now carrying out a study to identify these differences in a Brazilian sample. References [1] Roth M. Unitary or binary nature of classification of depressive illness and its implications for the scope of manic depressive disorder. J Affect Disord 2001;64:1-18. [2] Shorter E. The doctrine of the two depressions in historical perspective. Acta Psychiatr Scand Suppl 2007:5-13. [3] Parker G. Beyond major depression. Psychol Med 2005;35:467-74. [4] Parker G, Brotchie H. Major depression invites major concerns. Rev Bras Psiquiatr 2009;31(Suppl 1):S3-6. [5] Coryell W. The facets of melancholia. Acta Psychiatr Scand Suppl 2007:31-6. [6] Parker G. Defining melancholia: the primacy of psychomotor disturbance. Acta Psychiatr Scand Suppl 2007:21-30. [7] Parker G, Hadzi-Pavlovic D. Melancholia: a disorder of movement and mood. 1st ed. New York: Cambridge University Press; 1996. [8] Joyce PR, Mulder RT, Luty SE, McKenzie JM, Sullivan PF, Abbott RM, et al. Melancholia: definitions, risk factors, personality, neuroendocrine markers and differential antidepressant response. Aust N Z J Psychiatry 2002;36:376-83. [9] Parker G. Classifying depression: should paradigms lost be regained? Am J Psychiatry 2000;157:1195-203. [10] Hasin DS, Goodwin RD, Stinson FS, Grant BF. Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry 2005;62:1097-106. [11] Black DW, Bell S, Hulbert J, Nasrallah A. The importance of Axis II in patients with major depression. A controlled study. J Affect Disord 1988;14:115-22. [12] Whiffen VE, Parker GB, Wilhelm K, Mitchell PB, Malhi G. Parental care and personality in melancholic and nonmelancholic depression. J Nerv Ment Dis 2003;191:358-64. [13] Gotlib IH, Mount JH, Cordy NI, Whiffen VE. Depression and perceptions of early parenting: a longitudinal investigation. Br J Psychiatry 1988;152:24-7. [14] Fountoulakis KN, Iacovides A, Kaprinis S, Kaprinis G. Life events and clinical subtypes of major depression: a cross-sectional study. Psychiatry Res 2006;143:235-44. [15] Kohn Y, Zislin J, Agid O, Hanin B, Troudart T, Shapira B, et al. Increased prevalence of negative life events in subtypes of major depressive disorder. Compr Psychiatry 2001;42:57-63. [16] Cruz LN, de Almeida Fleck MP, Polanczyk CA. Depression as a determinant of quality of life in patients with chronic disease: data from Brazil. Soc Psychiatry Psychiatr Epidemiol 2010;45:953-61. [17] Berlim MT, Pargendler J, Caldieraro MA, Almeida EA, Fleck MP, Joiner TE. Quality of life in unipolar and bipolar depression: are there significant differences? J Nerv Ment Dis 2004;192:792-5. [18] Amorim P. Mini International Neuropsychiatric Interview (MINI): validação de entrevista breve para diagnóstico de transtornos mentais. Rev Bras Psiquiatr 2000;22:106-15. [19] Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6:278-96.
M.A.K. Caldieraro et al. / Comprehensive Psychiatry 54 (2013) 11–15 [20] Gorenstein C, Andrade LHSGd. Inventário de Depressão de Beck: propriedades psicométricas da versão em português. Rev Psiquiatr Clin 1998;25:245-50. [21] Parker G, Gladstone G, Wilhelm K, Hickie I, Mitchell P, HadziPavlovic D, et al. An aetiological model of non-melancholic depression: study design and validity of the measures. Aust N Z J Psychiatry 1998;32:104-11. [22] Fleck MP, Louzada S, Xavier M, Chachamovich E, Vieira G, Santos L, et al. Application of the Portuguese version of the abbreviated instrument of quality life WHOQOL-bref. Rev Saude Publica 2000;34: 178-83. [23] Berlim MT, Pavanello DP, Caldieraro MA, Fleck MP. Reliability and validity of the WHOQOL BREF in a sample of Brazilian outpatients with major depression. Qual Life Res 2005;14:561-4. [24] Parker G, Roussos J, Hadzi-Pavlovic D, Mitchell P, Wilhelm K, Austin MP. The development of a refined measure of dysfunctional parenting and assessment of its relevance in patients with affective disorders. Psychol Med 1997;27:1193-203. [25] Parker G, Manicavasagar V, Crawford J, Tully L, Gladstone G. Assessing personality traits associated with depression: the utility of a tiered model. Psychol Med 2006;36:1131-9. [26] Wild D, Grove A, Martin M, Eremenco S, McElroy S, Verjee-Lorenz A, et al. Principles of good practice for the translation and cultural adaptation process for patient-reported outcomes (PRO) measures: report of the ISPOR Task Force for Translation and Cultural Adaptation. Value Health 2005;8:94-104. [27] Baeza FLC, Caldieraro MAK, Pinheiro DO, Fleck MP. Translation and cross-cultural adaptation into Brazilian Portuguese of the Measure of Parental Style (MOPS)—a self-reported scale— according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommendations. Rev Bras Psiquiatr 2010;32:159-63. [28] Enns MW, Larsen DK, Cox BJ. Discrepancies between self and observer ratings of depression. The relationship to demographic, clinical and personality variables. J Affect Disord 2000;60:33-41.
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[29] Carter JD, Frampton CM, Mulder RT, Luty SE, Joyce PR. The relationship of demographic, clinical, cognitive and personality variables to the discrepancy between self and clinician rated depression. J Affect Disord 2010;124:202-6. [30] Fountoulakis KN, Iacovides A, Fotiou F, Nimatoudis J, Bascialla F, Ioannidou C, et al. Neurobiological and psychological correlates of suicidal attempts and thoughts of death in patients with major depression. Neuropsychobiology 2004;49:42-52. [31] Grunebaum MF, Galfalvy HC, Oquendo MA, Burke AK, Mann JJ. Melancholia and the probability and lethality of suicide attempts. Br J Psychiatry 2004;184:534-5. [32] Leventhal AM, Rehm LP. The empirical status of melancholia: implications for psychology. Clin Psychol Rev 2005;25:25-44. [33] Rush AJ, Weissenburger JE. Melancholic symptom features and DSMIV. Am J Psychiatry 1994;151:489-98. [34] Rubino IA, Zanasi M, Robone C, Siracusano A. Personality differences between depressed melancholic and non-melancholic inpatients. Aust N Z J Psychiatry 2009;43:145-8. [35] Parker G, Roussos J, Austin MP, Hadzi-Pavlovic D, Wilhelm K, Mitchell P. Disordered personality style: higher rates in non-melancholic compared to melancholic depression. J Affect Disord 1998;47:131-40. [36] Carter JD, Joyce PR, Mulder RT, Luty SE, Sullivan PF. Early deficient parenting in depressed outpatients is associated with personality dysfunction and not with depression subtypes. J Affect Disord 1999; 54:29-37. [37] Berlim MT, McGirr A, Fleck MP. Can sociodemographic and clinical variables predict the quality of life of outpatients with major depression? Psychiatry Res 2008;160:364-71. [38] Parker G, Mitchell P, Wilhelm K, Menkes D, Snowdon J, Schweitzer I, et al. Are the newer antidepressant drugs as effective as established physical treatments? Results from an Australasian clinical panel review. Aust N Z J Psychiatry 1999;33:874-81. [39] Parker G, Roy K, Wilhelm K, Mitchell P. Assessing the comparative effectiveness of antidepressant therapies: a prospective clinical practice study. J Clin Psychiatry 2001;62:117-25.
Comprehensive Psychiatry 54 (2013) 11 – 15 www.elsevier.com/locate/comppsych
Clinical differences between melancholic and nonmelancholic depression as defined by the CORE system Marco Antonio Knob Caldieraro a,⁎, Fernanda Lucia Capitanio Baeza a , Diesa Oliveira Pinheiro a , Mariana Rangel Ribeiro a , Gordon Parker b , Marcelo P. Fleck a a
Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-003, Brazil b Black Dog Institute, Prince of Wales Hospital, Randwick, NSW 2031, Australia
Abstract Background: The definition and delineation of melancholia have remained elusive for an extended period. A longstanding signal of psychomotor disturbance has been operationalized via the observer-rated CORE measure and with CORE-assigned melancholic and nonmelancholic compared in several Australian studies. Replication studies in other regions have not previously been reported. This study compares Brazilian patients with melancholic and nonmelancholic depression according to the CORE measure of psychomotor disturbance in terms of clinical characteristics, suicide ideation, stressful life events, quality of life, parental care, and personality styles. Methods: A total of 181 patients with unipolar major depression attending a tertiary care outpatient service in Brazil were evaluated in relation to melancholic status and study variables. Results: The CORE-assigned melancholic patients presented higher symptom severity, greater prevalence of suicide ideation, and Axis I comorbidities than nonmelancholics. Scores of dysfunctional personality styles and dysfunctional parental care measures were also higher among melancholics. Quality-of-life scores were low in both groups. Limitations: The absence of a criterion standard for the diagnosis of melancholia and the use of medication can be potential limitations of the study. Conclusion: Differences suggest that CORE-assigned melancholia defines a distinct group of patients and probably a disorder distinct from nonmelancholic depression not only in quantitative but also in qualitative aspects. © 2013 Elsevier Inc. All rights reserved.
1. Introduction Most of the discussion about the concept of melancholia is linked to the debate as to whether depression should be classified as a unitary or binary disorder [1,2]. By the time that Diagnostic and Statistical Manual of Mental Disorders (DSM), Third Edition, was published, there was not enough empirical support for the binary model, so the manual favored a dimensional model. Nevertheless, a specifier for major depression with melancholia was included, keeping the question about the status of melancholia open [3]. The DSM Fourth Edition (DSM-IV) model is similar to that of DSM Third Edition. However, the melancholic specifier of ⁎ Corresponding author. Rua Ramiro Barcellos, 2350. 4º andar, Serviço de Psiquiatria, 90035-003 Porto Alegre, Rio Grande do Sul, Brazil. Tel.: +55 51 3359 8264; fax: +55 51 3359 8264. E-mail address: [email protected] (M.A.K. Caldieraro). 0010-440X/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.comppsych.2012.05.012
DSM-IV is not broadly used, probably because its assignments differ little from the overall major depression [4]. Many features have been used to define melancholia [5,6]. Parker et al [7] judged that observable psychomotor disturbance (PMD) was one of the most longstanding clinical markers of melancholic depression. They developed the CORE measure to operationalize the assessment of PMD. This instrument was validated by comparison with clinical and neuroendocrine measures [6,8]. The discrimination of melancholic depression according to PMD is part of a larger model for classifying depression across 3 subtypes (nonmelancholic, melancholic, and psychotic) [9]. Studies independent of the Australian group have not been published, inviting the current study. Depressive subtypes have been shown to differ across several variables, including psychiatric comorbidities [10], personality [11,12], parental care [12,13], stressful life events [14,15], and quality of life (QOL) [16,17]. The aim
12
M.A.K. Caldieraro et al. / Comprehensive Psychiatry 54 (2013) 11–15
of this study is to evaluate if patients with melancholic depression, according to the CORE measure, differentiated from nonmelancholic subjects on clinical characteristics described above and in terms of symptoms severity, suicide ideation, and other clinical features.
2. Materials and methods 2.1. Subjects All outpatients (n = 232) referred to the Mood Disorders Program of the Hospital de Clínicas de Porto Alegre during the study period were enrolled. The outpatient tertiary care service focuses on managing unipolar depressive disorders in adults. Patients experiencing a major depressive episode were included. Exclusion criteria were a previous history of mania or hypomania or inability to understand the research instruments. The investigation was approved by the medical ethics committee of the Hospital de Clínicas de Porto Alegre, and all participants provided written, informed consent. 2.2. Measures Major depression, current and past episodes, and psychiatric comorbidities were diagnosed according to the Mini International Neuropsychiatric Interview, Brazilian version [18]. Severity of depression was assessed by the Hamilton Depression Rating Scale (HAM-D) [19] and the Beck Depression Inventory (BDI) [20]. Assignment to melancholic and nonmelancholic groups was undertaken by the CORE measure. A CORE score greater than or equal to 8 held to indicate likely melancholia [6] and was adopted in this study. The presence of suicidal ideation was determined by taking into account the BDI suicide item. The rating of “I don't have any thoughts of killing myself” was considered as no suicide ideation. The other statements were considered as indicative of suicide ideation. The presence of life event stressors during the 12 months before the starting of the current episode was assessed by a self-reported inventory, used by Parker et al [21] in a previous study. Quality of life was assessed by the World Health Organization's Quality of Life Instrument short version, Brazilian version [22,23]. Parental care was assessed by the Measure of Parental Style (MOPS) [24]. The Temperament and Personality (T&P) questionnaire was used to study personality styles. This instrument seeks to quantify personality constructs providing risk to depression [25]. We performed a translation and cultural adaptation of the CORE, MOPS, and T&P instruments following the guideline from the Translation and Cultural Adaptation group of the International Society for Pharmacoeconomics and Outcomes Research [26]. This process was described elsewhere using MOPS as example [27].
2.3. Statistical analysis Data were analyzed with the SPSS version 16.0 (SPSS, Inc, Chicago, IL). Continuous data were compared by Student t test for normally distributed data and by the Mann-Whitney U test for data with nonnormal distributions. Categorical variables were compared by the χ 2 test; in cases with the expected frequency less than 5 in more than 20% of categories, Fisher exact test was used. All tests were 2 tailed, and P b .05 was used as the criterion for statistical significance.
3. Results From the 232 patients evaluated, 181 were included for analysis. Reasons for exclusion were patient not presenting a current major depression episode (n = 17), history of mania or hypomania (n = 24), and patient unable to understand the research instruments (n = 1). Forty-five patients (24.9%) met the 8-or-more CORE cutoff criterion score, with the remaining 136 patients (75.1%) assigned as having nonmelancholic depression. There were no differences in sociodemographic variables between groups (Table 1). Severity of depression was different between groups when assessed by the HAM-D. The score on this scale was higher in the melancholic patients (difference of means, 4.45; 95% confidence interval [CI], 2.76-6.14). The effect size for this difference was 0.84. Scores on the BDI, a self-rated scale, were also higher in the melancholic group, but this difference did not achieve statistical significance. Table 1 Demographic characteristic
Age, mean (SD) Sex, n (%) Female Ethnicity, n (%) White African American Other Marital status, n (%) Married Never Married Divorced Widowed Education, n (%) Nonalphabetized Primary school High school College Employment status, n (%) Employed Unemployed Retired Disablement benefit Unwaged domestic work Other
Nonmelancholic (n = 136)
Melancholic (n = 45)
P
49.60 (11.4)
46.13 (12.1)
.084 .279
123 (90.4)
38 (84.4)
109 (80.1) 16 (11.8) 11 (8.1)
34 (75.6) 6 (13.3) 5 (11.1)
75 (55.1) 26 (19.1) 16 (11.8) 19 (14.0)
26 (57.8) 11 (24.4) 6 (13.3) 2 (4.4)
8 (5.9) 66 (48.5) 54 (39.7) 8 (5.9)
2 (4.4) 25 (55.6) 14 (31.1) 4 (8.9)
26 (19.1) 28 (20.6) 28 (20.6) 31 (22.8) 10 (7.4) 13 (9.6)
10 (22.2) 12 (26.7) 3 (6.7) 8 (17.8) 6 (13.3) 6 (13.3)
.776
.358
.668
.241
M.A.K. Caldieraro et al. / Comprehensive Psychiatry 54 (2013) 11–15
The correlation of these 2 measures was moderate (r = 0.44, P b .001). Clinical differences between groups are described in Table 2. Suicide ideation was more prevalent in melancholic depression. The prevalence ratio (PR) was 1.43 (95% CI, 1.17-1.75). Although not formally statistically significant, the melancholic patients had a higher prevalence of past major depression episode, medical comorbidity, family history of depression, and psychiatric disorder. The prevalence of serious life event stressor exceeded 85% in both groups, with no significant differences (P = .66). The presence of any Axis I psychiatric comorbidity was high in both groups but significantly higher in melancholic depression (PR, 1.19; 95% CI, 1.06-1.33). When comorbidities were analyzed individually, statistically significant difference was found only for social phobia, which was higher in melancholic depression (PR, 1.78; 95% CI, 1.212.63). Other anxiety disorders also showed a tendency to be more prevalent in melancholia. Both groups showed low QOL scores. Despite not achieving statistical significance, all scores were lower in melancholic depression. Scores for each domain were, respectively, for melancholics and nonmelancholics: physical health, 30.93 vs 31.14 (P = .94); psychological, 29.73 vs 32.14 (P = .40); social relationships, 43.56 vs 46.69 (P = .42); environment, 40.86 vs 43.88 (P = .25); and global QOL, 33.81 vs 34.74 (P = .76).
Table 2 Clinical characteristics
HAM-D, mean (SD) BDI, mean (SD) Suicidal ideation Past MDE, n (%) Psychiatric comorbidities, n (%) Presence of any comorbidity Social phobia Panic disorder Agoraphobia without panic OCD PTSD Alcohol dependence Substance dependence Anorexia Bulimia GAD Medical comorbidity, n (%) FH psychiatric disorder, n (%) FH depression, n (%) Life event stressor, a n (%)
Nonmelancholic (n = 136)
Melancholic (n = 45)
P
18.7 (4.8) 32.4 (10.9) 77 (57.5) 77 (56.6)
23.1 (5.5) 35.3 (9.6) 37 (82.2) 20 (46.5)
b.001 .124 .003 .246
107 (78.7) 39 (28.7) 12 (10.9) 28 (20.6) 23 (16.9) 13 (9.6) 3 (2.2) 7 (5.1) 0 (0.0) 2 (1.5) 69 (50.7) 115 (84.6) 109 (82.6) 96 (72.7) 111 (86.0)
42(93.3) 23 (51.1) 9 (20.0) 15 (33.3) 10 (22.2) 6 (13.3) 1 (2.2) 0 (0.0) 0 (0.0) 1 (2.2) 29 (64.4) 39 (86.7) 36 (80.0) 32 (71.1) 39 (88.6)
.025 .006 .090 .082 .424 .574 1.000 .195 1.000 .110 .731 .698 .834 .662
Substance dependence is dependence of a substance other than alcohol. MDE indicates major depressive episode; OCD, obsessive-compulsive disorder; PTSD, posttraumatic stress disorder; GAD, generalized anxiety disorder; FH, family history. a Presence of at least 1 life event classified by the patient as severe, extreme, or catastrophic in the 12 months before the starting of the current depressive episode.
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Maternal abuse, assessed by the MOPS, were higher among melancholics (median, 5.0 vs 2.0; P = .026). There were no differences in the subscales of maternal indifference and overcontrol. There were no differences in scores for paternal care. Regarding personality dysfunction as assessed by the T&P measure of personality styles, those with melancholic depression presented higher scores on personal reserve (17.36 vs 14.30, P = .005) and social avoidance (16.33 vs 14.27, P = .012). There were no statistically significant differences on the 6 other constructs.
4. Discussion Depression severity was greater in melancholic patients when assessed by the HAM-D. The difference was large as reflected by the effect size. This finding demonstrates the capacity of the CORE measure to discriminate 2 groups of depression according to the severity of symptoms in a clinician-rated scale. It also supports the model proposed by Parker et al, which suggests a gradient of symptom severity lower in nonmelancholic, intermediate in melancholic, and higher in psychotic depression [7]. However, when severity of depression was assessed by the BDI, a self-rated scale, no difference was found between the groups. The moderate correlation found between HAM-D and BDI in this sample is consistent with most studies [28]. Patients with moderate to severe depression and those with the nonmelancholic subtype tend to score higher in self-report ratings [29]. These observations could explain the lack of difference in BDI scores. The finding that patients with melancholic depression, as assigned by CORE, had a greater prevalence of suicide ideation is relevant. Suicide is a major problem in psychiatry, and depression is the nosological entity most associated with suicidal behavior [30], but predicting which depressive patients will attempt suicide is a difficult task. A study using DSM criteria for melancholia found an association of this subtype with more serious past suicide attempt and the probability of future attempts [31]. However, studies using DSM or Research Diagnostic Criteria (RDC) constructs of melancholia are inconclusive about the association of melancholia and suicide [32]. Although measuring only suicide ideation, the present study suggests that patients with CORE-defined melancholia are a distinct group with increased suicide risk. Classical descriptions associate melancholia with genetic determinants, suggesting a higher prevalence of family history of depression in this subtype. In our sample, the prevalence was similar across the melancholic and nonmelancholic groups. Although diverging from the classical descriptions, this result is similar to most empirical studies [33]. Melancholia is also classically described as not being associated distinctly with stressful life events. In this study, melancholic patients presented a high prevalence of such
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events and similar to the nonmelancholic group. This result also diverges from classical description but agrees with most empirical studies [32]. The higher prevalence of Axis I comorbidity in the melancholic group was underpinned by anxiety. Although a significant difference was found only for social phobia, a tendency for higher rates of panic disorder and agoraphobia was found among the melancholic patients. Interestingly, the personality styles higher in the melancholic subgroups were personal reserve and social avoidance, traits related to social phobia. It could be that personality traits associated with less social interaction predispose to both social phobia and to melancholia. Another possibility is that social withdrawal is a manifestation of melancholia with symptoms intense enough to produce a clinical diagnosis of social phobia. The high social anxiety traits may be a characteristic of Brazilian population, as opposing results were found in an Italian study using the same instruments [34]. An Australian study found a higher prevalence of avoidant personality disorder in nonmelancholics [35]. Another study found a higher prevalence of avoidant personality disorder in melancholics and no difference in social phobia [8]. Higher maternal abuse among the melancholic patients suggests that it might lead to melancholic depression. However, this result should be considered carefully because it is divergent from other studies [24,36]. Both groups presented low QOL scores in all domains without differences between melancholic and nonmelancholic depression, suggesting that the impact of depression on QOL is intense but not related to the depressive subtype. This is the first study to compare QOL in nonmelancholic and melancholic depression assigned by the CORE measure, although 1 study found similar results using the DSM-IV criteria of melancholia [37]. A limitation of this study is that it was conducted in a tertiary care facility where most patients had already been medicated before referral. Thus, they could have achieved some improvement of the PMD by the time of the interview. Another limitation is that there is no criterion standard for the diagnosis of melancholia. The CORE measure is subjected to variability and presents no absolute sensibility and specificity [6]. Despite these limitations, we found that melancholic depression as defined by the CORE measure differentiated from the nonmelancholic subtype in severity of symptoms, suicide ideation, Axis I comorbidities, personality styles, and parental care. Such differences reinforce melancholia as a distinct disorder. They also remark the importance of PMD in the diagnosis of melancholia and contribute to validate the CORE for assessment of PMD. As a future perspective, the discrimination of distinct depressive subtypes will be of greater value if it helps to identify specific treatments for each subtype. Some studies compared the response to pharmacologic treatment in melancholic and nonmelancholic depression according to
CORE. Most of them were carried out in Australia by Parker et al [38,39]. Results suggest that melancholics present a better response to tricyclic antidepressants than to selective serotonin reuptake inhibitors, whereas response was similar to both classes of drugs among nonmelancholics. Interestingly, this difference seems to be increased in older patients [39]. A study independent of the Australian group found an unexpected better response to fluoxetine compared with nortriptyline in severe melancholia [8]. Our group is now carrying out a study to identify these differences in a Brazilian sample. References [1] Roth M. Unitary or binary nature of classification of depressive illness and its implications for the scope of manic depressive disorder. J Affect Disord 2001;64:1-18. [2] Shorter E. The doctrine of the two depressions in historical perspective. Acta Psychiatr Scand Suppl 2007:5-13. [3] Parker G. Beyond major depression. Psychol Med 2005;35:467-74. [4] Parker G, Brotchie H. Major depression invites major concerns. Rev Bras Psiquiatr 2009;31(Suppl 1):S3-6. [5] Coryell W. The facets of melancholia. Acta Psychiatr Scand Suppl 2007:31-6. [6] Parker G. Defining melancholia: the primacy of psychomotor disturbance. Acta Psychiatr Scand Suppl 2007:21-30. [7] Parker G, Hadzi-Pavlovic D. Melancholia: a disorder of movement and mood. 1st ed. New York: Cambridge University Press; 1996. [8] Joyce PR, Mulder RT, Luty SE, McKenzie JM, Sullivan PF, Abbott RM, et al. Melancholia: definitions, risk factors, personality, neuroendocrine markers and differential antidepressant response. Aust N Z J Psychiatry 2002;36:376-83. [9] Parker G. Classifying depression: should paradigms lost be regained? Am J Psychiatry 2000;157:1195-203. [10] Hasin DS, Goodwin RD, Stinson FS, Grant BF. Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry 2005;62:1097-106. [11] Black DW, Bell S, Hulbert J, Nasrallah A. The importance of Axis II in patients with major depression. A controlled study. J Affect Disord 1988;14:115-22. [12] Whiffen VE, Parker GB, Wilhelm K, Mitchell PB, Malhi G. Parental care and personality in melancholic and nonmelancholic depression. J Nerv Ment Dis 2003;191:358-64. [13] Gotlib IH, Mount JH, Cordy NI, Whiffen VE. Depression and perceptions of early parenting: a longitudinal investigation. Br J Psychiatry 1988;152:24-7. [14] Fountoulakis KN, Iacovides A, Kaprinis S, Kaprinis G. Life events and clinical subtypes of major depression: a cross-sectional study. Psychiatry Res 2006;143:235-44. [15] Kohn Y, Zislin J, Agid O, Hanin B, Troudart T, Shapira B, et al. Increased prevalence of negative life events in subtypes of major depressive disorder. Compr Psychiatry 2001;42:57-63. [16] Cruz LN, de Almeida Fleck MP, Polanczyk CA. Depression as a determinant of quality of life in patients with chronic disease: data from Brazil. Soc Psychiatry Psychiatr Epidemiol 2010;45:953-61. [17] Berlim MT, Pargendler J, Caldieraro MA, Almeida EA, Fleck MP, Joiner TE. Quality of life in unipolar and bipolar depression: are there significant differences? J Nerv Ment Dis 2004;192:792-5. [18] Amorim P. Mini International Neuropsychiatric Interview (MINI): validação de entrevista breve para diagnóstico de transtornos mentais. Rev Bras Psiquiatr 2000;22:106-15. [19] Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6:278-96.
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