- Email: [email protected]
Depressive symptoms in Parkinson's disease
Available online at www.sciencedirect.com
Comprehensive Psychiatry 53 (2012) 727 – 731 www.elsevier.com/locate/comppsych
Depressive symptoms in Parkinson's disease Armando Piccinni a , Donatella Marazziti a , Antonello Veltri a,⁎, Roberto Ceravolo b , Carla Ramacciotti a , Marina Carlini a , Alessandro Del Debbio a , Elisa Schiavi a , Ubaldo Bonuccelli b , Liliana Dell'Osso a a
Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Via Roma 67, 56126 Pisa, Italy b Department of Neuroscience, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy
Abstract Objective: We aimed to investigate the relationship between the presence and severity of depression and the degree of motor and functional disability in Parkinson's disease (PD). Methods: One hundred twenty-two outpatients with PD were enrolled in a neurology department: 65 satisfied the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria for major depression, and 57 did not (PD-C). Depressive symptoms were assessed by means of the Hamilton Rating Scale for Depression (HRSD), and the PD severity was assessed according to the Hoehn and Yahr System. Activities of daily living and motor symptoms were measured by the Unified PD Rating Scale (UPDRS), parts II and III. Results: Twenty-nine patients had a mild depression (HRSD total score ranging between 8 and 17), 30 had a moderate depression (HRSD total score ranging between 18 and 24), and 6 had a severe depression (HRSD total score, ≥25). By comparing the 3 groups of patients, it emerged that those with a severe depression showed significantly higher scores at the UPDRS II, UPDRS III, and HY scales than did PD-C or patients with a mild depression. Moreover, patients with a moderate depression scored significantly higher on the UPDRS II, UPDRS III, and HY scales than did PD-C or those with a mild depression. Conclusions: Our findings suggest that depression and motor symptoms/well-being are highly intertwined in patients with PD. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Parkinson's disease (PD) is a neurodegenerative disorder characterized by bradykinesia, rigidity, and rest tremor [1]. Depressive disorders may affect between 2.7% and 90% of patients with PD and are associated with increased disability and reduced quality of life, although they are often underestimated [2-9]. Risk factors associated with depression include also a longer PD duration and a greater impairment in daily activities [10]. The investigation of depression in PD is complicated by a certain degree of overlap between
⁎ Corresponding author. Tel.: +39 050 992642; fax: +39 050 992925. E-mail addresses: [email protected] (A. Piccinni), [email protected] (D. Marazziti), [email protected] (A. Veltri), [email protected] (R. Ceravolo), [email protected] (A. Del Debbio), [email protected] (E. Schiavi), [email protected] (U. Bonuccelli), [email protected] (L. Dell'Osso). 0010-440X/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.comppsych.2011.11.002
the 2 symptom patterns: psychomotor retardation or agitation, hypomimia, fatigue, or loss of appetite. An increasing number of evidence suggests that depression in PD might be secondary to the underlying neuroanatomical degeneration, rather than a simple reaction to the psychosocial stress and disability [11]. Parkinson's disease is, in fact, characterized by degeneration of the subcortical nuclei, such as the ventral tegmental area, hypothalamus, dorsal raphe, and locus coeruleus; and some of these have been implicated also in the pathophysiology of depression [12,13]. A decreased density of serotonin neurons in the dorsal raphe and of dopamine neurons in the ventral tegmental area is a common finding detected in postmortem brain specimens of patients with PD with a history of depression [12,13]. The different degree of degeneration of subcortical structures has been linked to the clinical heterogeneity of the non-motor syndromes of PD, in particular, to depression, psychosis, and even dementia [12,14]. The correlation of depressive symptoms with specific clinical features of PD has been demonstrated as well: patients with right-sided motor symptoms and with the
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A. Piccinni et al. / Comprehensive Psychiatry 53 (2012) 727–731
akinetic rigid type of PD show a higher comorbidity with depression, if compared with the classic type of PD (tremor, rigidity, and/or bradykinesia) [15,16]. Some studies suggest that non-motor symptoms such as autonomic disorders and depression are important factors influencing the quality of life of patients with PD [5,17]. In particular, it has been proposed that a consistent degree of physical disability in PD is associated with depression, but opposite findings are also available [18-21]. Depression may provoke a greater impairment of fine-motor skills, and subsequently, it would increase the disability associated with a given level of motor manifestations [22-24]. The aim of the present study was to explore how different degrees of depressive symptoms, as assessed by the Hamilton Rating Scale for Depression (HRSD), may contribute to an increased disability in patients with PD. 2. Methods 2.1. Patients A sample of 122 patients with idiopathic PD was consecutively recruited at the Movement Disorders Unit of the Department of Neuroscience of the Pisa University (Italy). Diagnosis of idiopathic PD was made in agreement with the UK PD Society Brain Bank clinical criteria for PD [25]. There was no age limit for inclusion in the study. Patients with other parkinsonian syndromes, or presenting cognitive deterioration, as evaluated by the Mini Mental State Examination (b23), or a positive history for drug-induced psychosis, brain tumors, cerebrovascular accidents, late outcomes of brain injuries, epilepsy, or pregnancy were excluded. All patients were given full information about the protocol and gave written informed consent to the study, which was approved by the local ethics committee. 2.2. Assessment The patients were assessed by a neurologist (R.C.) by means of the Unified PD Rating Scale (UPDRS) and were staged according to the Hoehn and Yahr System (H/Y) [26,27]. The UPDRS is the criterion standard of motor measurement in PD and has proven highly effective in clinical management and research [27]. It consists of 4 parts: I, mentation, behavior, and mood; II, activities of daily living (ADL); III, motor examination; and IV, complications of therapy. For the purpose of our study, we used sections II and III of UPDRS. The H/Y scale measures the severity of the disease and is based on lateralization of the symptoms and balance evaluation. Higher scores on both scales indicate a more severe impairment. Other clinical features such as akinetic-rigid vs tremor-dominant form, instability, dyskinesias, “on-off” periods, PD duration, and antiparkinsonian treatment were also collected. All patients underwent a psychiatric evaluation performed by a psychiatrist (A.P.), and current and lifetime diagnoses were carried out according to the Diagnostic and Statistical Manual of Mental
Disorder, Fourth Edition, Text Revision (DSM-IV-TR) criteria by the Structured Clinical Interview for DSM [28,29]. The 21-item HRSD was used for symptom assessment [30]. The HRSD is the most widely used and accepted measure for evaluating the severity of depression [31]; in particular, in patients with PD, it shows good sensitivity and specificity [32]. The HRSD total score between 8 and 17 identifies a mild depression; between 18 and 24, a moderate depression; and ≥25, a severe depression. 2.3. Statistical analyses Because data were not normally distributed, as shown by the Kolmogorov-Smirnov test, non-parametric tests were used. The Kruskal-Wallis test (KW) with post-hoc pair-wise Mann-Whitney multiple comparisons and χ 2 test were used to compare continuous and categorical variables across groups, respectively. A P value less than .05 was considered significant. Statistical analyses were performed by means of the Statistical Package for Social Science (version 12.5; SPSS, Chicago, IL). 3. Results Seventy patients were men, and 52 were women (mean ± SD age, 67.01 ± 8.54 years); the disease duration (mean ± SD) was 6.90 ± 4.80 years. Eighty-seven patients were nonfluctuating, and 35 had on-off phenomena. One hundred twelve patients were treated with L-dopa or dopamine agonists, whereas 10 were drug-free. With regard to the types of dopaminergic treatment, the sample could be divided into 3 subgroups: 56 patients (50%) were taking L-dopa and dopamine agonists (21 were taking pergolide; 19, ropinirole; and 16, pramipexole); 45 (40.2%), L-dopa alone; and 11 (9.8%), dopamine agonists alone (4 were taking ropinirole; 4, pergolide; and 3, pramipexole). No patient was receiving deep brain stimulation. Sixty-five patients (52.2%) of the total of 122 satisfied the DSM-IV criteria for current major depression: 29 (44.6%) had a mild depression, 30 (46.1%) had a moderate depression, and 6 (9.3%) had a severe depression (Table 1). Besides the current episode, 5 patients had a positive history of lifetime depression, as assessed by the Structured Clinical Interview for DSM. Patients with and without depression were similar in terms of age, sex, and duration of illness. On the contrary, the UPDRS II (KW: z = 8.2, P = .041), UPDRS III (KW: z = 12.0, P = .007), and H/Y (KW: z = 9.8, P = .020) scores were significantly higher in depressed than in non-depressed patients. The same was true for tremor (χ 2: z = 22.8, P = .029), instability (χ 2: z = 22.8, P = .030), or dyskinesias (χ 2: z = 27.6, P = .006) and duration of L-dopa treatment (KW: z = 7.7, P = .000) (Table 2). The post-hoc analyses showed that patients with severe depression had significantly higher scores on the UPDRS II, UPDRS III, and H/Y scales compared with those with mild or without depression. Moreover, patients with moderate
A. Piccinni et al. / Comprehensive Psychiatry 53 (2012) 727–731
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Table 1 Demographic characteristics of 122 PD patients with (PD-D) and without (PD-C) depression HRSD total score PD-D (n = 65)
Sex Female Male Age (y) Duration of PD (mo)
F
P
2.64
.451
1.9 2.2
.130 .089
PD-C (n = 57)
8-17, mild depression (n = 29)
18-24, moderate depression (n = 30)
≥25, severe depression (n = 6)
15 (51.7%) 14 (48.3%) 65.4 ± 6.8 5.4 ± 4.8
14 (46.7%) 16 (53.3%) 66.9 ± 8.0 8.5 ± 5.7
3 (50%) 3 (50%) 74.5 ± 6.3 7.6 ± 1.7
depression scored significantly higher on the UPDRS III and H/Y than mildly depressed or nondepressed patients.
4. Discussion The purpose of this study was to assess the possible impact of depression, as well as of its severity, on physical disability and functioning in a cohort of patients with PD. The results showed that about 53% (n = 65) of patients with PD were experiencing a clinically relevant depression. This is consistent with some previous findings, although it should be underlined that the prevalence rates of depression range widely between 2.7% and 90%, according to different studies [8,33]. The nature of the population studied, the heterogeneity of diagnostic criteria, the different assessment techniques, the statistical analyses used, and the type of depressive disorders may explain this wide variation [10]. In our study, by using the HRSD cut-off scores of 8 to 17, 18 to 24, and 25 or greater for depression severity, 23.8% of
20 (35.1%) 37 (64.9%) 67.1 ± 9.5 6.7 ± 4.2
patients with PD had a mild depression, 24.6% had a moderate depression, and 4.9% had a severe depression. In addition, those patients with depressive symptoms ranging between mild and severe, scored higher on different measures of PD severity and functioning in daily living than did non-depressed patients: the higher the depressive score, the higher the physical and functioning impairments. Furthermore, the most patients with severe depression reported the worst outcome on the UPDRS II, UPDRS III, and H/Y scales. The available data on the association between depression and PD severity are conflicting, with most of them reporting a positive association and some reporting no correlation [15,34,35]. The results of the current study are consistent with those showing that a diagnosis of depression was related to higher scores on the UPDRS II (ADL) and UPDRS III (motor examination) [21,24]. However, to our knowledge, the present study is the first to examine the effect of depressive symptom severity on physical disability and functioning by subtyping depressed patients with PD
Table 2 Comparisons of PD patients with (PD-D) and without (PD-C) depression HRSD total score PD-D (n = 65)
Scores on clinical measures UPDRS II UPDRS III MMSE H/Y scale Tremor Rigidity Instability On-off phenomena Dyskinesias L-Dopa treatment Duration of L-Dopa treatment (mo)
F
P
8.2 12.0 1.8 9.8 22.8 14.25 22.79 19.43 27.59 6.24 7.75
.041 .007 .152 .020 .029 .114 .030 .079 .006 .100 .000
PD-C (n = 57)
8-17, mild depression (n = 29)
18-24, moderate depression (n = 30)
≥25, severe depression (n = 6)
12.8 ± 4.2 16.1 ± 5.9 27.8 ± 1.9 1.4 ± 0.6 22 (75.8%) 22 (75.8%) 14 (48.2%) 5 (17.2%) 4 (13.8%) 20 (61.4%) 49.5 ± 56.2
14.6 ± 4.9 21.7 ± 10.0 27.5 ± 1.9 1.8 ± 0.6 21 (70.0%) 22 (73.3%) 20 (66.7%) 12 (40.1%) 14 (46.6%) 28 (93.3%) 99.6 ± 87.4
16.8 ± 2.9 22.3 ± 6.1 25.8 ± 1.9 2.0 ± 0.0 3 (50.0%) 5 (83.4%) 4 (66.7%) 2 (33.3%) 4 (66.7%) 5 (83.3%) 120.2 ± 21.9
12.8 ± 2.9 16.0 ± 4.3 27.3 ± 1.9 1.5 ± 0.6 39 (68.4%) 45 (79.0%) 33 (57.9%) 16 (28.1%) 22 (38.6%) 48 (84.2%) 47.4 ± 34.8
Post-hoc tests: UPDRS II: PD-C b PD-D (severe depression); z = −2.699, P = .007; PD-D (mild depression) b PD-D (severe depression); z = −2.261, P = .025; UPDRS III: PD-C b PD-D (moderate depression); z = −2.073, P = .038; PD-C b PD-D (severe depression); z = −2.655, P = .008; PD-D (mild depression) b PD-D (moderate depression); z = −2.422, P = .015; PD-D (mild depression) b PD-D (severe depression); z = −2.467, P = .014; H/Y scale: PD-C b PD-D (moderate depression); z = −2.064, P = .039; PD-C b PD-D (severe depression); z = −2.038, P = .042; PD-D (mild depression) b PD-D (moderate depression); z = −2.317, P = .021; PD-D (mild depression) b PD-D (severe depression); z = −2.278, P = .023. MMSE indicates Mini Mental State Examination.
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according to the HRSD total score. Our results seem to confirm that severely depressed patients with PD may be significantly more disabled than mildly depressed or nondepressed ones. The characterization of depressive symptoms in PD along a continuum by using the “severity” parameter may, thus, permit to ascertain more accurately the effects of depression on physical status and functioning and, perhaps, may be of help to identify clinical phenotypes of patients with PD with different degrees of disability. In our sample, the depression severity was significantly associated with higher scores on the H/Y scale, a longer duration of L-dopa treatment, and the presence of some specific clinical features of PD, such as tremor, gait instability, and dyskinesias. Generally, depression has been associated with the akinetic rigid type of PD, bradykinesia, and gait instability compared with tremor-dominant forms [15,16]. Our results confirm these findings and show a trend toward a high prevalence of dyskinesias and gait instability in severely and moderately depressed patients. When interpreting these data, several limitations should be acknowledged. First, the sample was restricted to individuals seeking treatment in a neurology department, and this may limit the generalizability of these data. Patients with PD not receiving treatment and those seeking for treatment from other types of specialists may have different profiles. Furthermore, certain confounding factors that potentially could affect health status are not taken into account (ie, severity of other medical conditions, diet, exercise, and other lifestyle factors). Another limitation is the cross-sectional nature of the study, which does not permit to establish whether physical and functional impairment may affect depression or vice versa. Again, the number of patients with different severity of depression was not similar; in particular, the patients with the most severe symptoms were only 6, and this might impair the statistical analyses. Furthermore, for the small sample size, we could not compare patients with only current vs those with current and lifetime depression. Limited bias due to multiple comparisons should also be considered.
4. Conclusion In conclusion, our results confirm the high prevalence of depression in patients with PD. In addition, they support the notion that depression and motor disability or functioning in daily activities are strictly intertwined. Therefore, the presence of depression in patients with PD should be routinely assessed in the clinical practice because it might significantly influence motor symptoms and well-being. References [1] Parkinson J. An essay on the shaking palsy (reprinted from 1817). J Neuropsychiatry Clin Neurosci 2002;14(2):223-36.
[2] Cole SA, Woodard JL, Juncos JL, Kogos JL, Youngstrom EA, Watts RL. Depression and disability in Parkinson's disease. J Neuropsychiatry Clin Neurosci 1996;8(1):20-5. [3] Schrag A, Jahanshahi M, Quinn N. How does Parkinson's disease affect quality of life? A comparison with quality of life in the general population. Mov Disord 2000;15(6):1112-8. [4] Slaughter JR, Slaughter KA, Nichols D, Holmes SE, Martens MP. Prevalence, clinical manifestations, etiology, and treatment of depression in Parkinson's disease. J Neuropsychiatry Clin Neurosci 2001;13(2): 187-96. [5] Yamamoto M. Depression in Parkinson's disease: its prevalence, diagnosis, and neurochemical background. J Neurol 2001;248(Suppl 3):III5-11. [6] Marsh L, McDonald WM, Cummings J, Ravina B, NINDS/NIMH Work Group on Depression and Parkinson's Disease. Provisional diagnostic criteria for depression in Parkinson's disease: report of an NINDS/NIMH Work Group. Mov Disord 2006;21(2):148-58. [7] Ravina B, Camicioli R, Como PG, Marsh L, Jankovic J, Weintraub D, et al. The impact of depressive symptoms in early Parkinson disease. Neurology 2007;69(4):342-7. [8] Reijnders JS, Ehrt U, Weber WE, Aarsland D, Leentjens AF. A systematic review of prevalence studies of depression in Parkinson's disease. Mov Disord 2008;23(2):183-9. [9] Riedel O, Heuser I, Klotsche J, Dodel R, Wittchen HU, GEPAD Study Group. Occurrence risk and structure of depression in Parkinson disease with and without dementia: results from the GEPAD Study. J Geriatr Psychiatry Neurol 2010;23(1):27-34. [10] Jasinska-Myga B, Putzke JD, Wider C, Wszolek ZK, Uitti RJ. Depression in Parkinson's disease. Can J Neurol Sci 2010;37(1): 61-6. [11] McDonald WM, Richard IH, DeLong MR. Prevalence, etiology, and treatment of depression in Parkinson's disease. Biol Psychiatry 2003;54(3):363-75. [12] Paulus W, Jellinger K. The neuropathologic basis of different clinical subgroups of Parkinson's disease. J Neuropathol Exp Neurol 1991; 50(6):743-55. [13] Brown AS, Gershon S. Dopamine and depression. J Neural Transm Gen Sect 1993;91(2-3):75-109. [14] Jellinger KA, Paulus W. Clinico-pathological correlations in Parkinson's disease. Clin Neurol Neurosurg 1992;94(Suppl):S86-8. [15] Cummings JL. Depression and Parkinson's disease: a review. Am J Psychiatry 1992;149(4):443-54. [16] Starkstein SE, Preziosi TJ, Bolduc PL, Robinson RG. Depression in Parkinson's disease. J Nerv Ment Dis 1990;178(1):27-31. [17] Borek LL, Amick MM, Friedman JH. Non-motor aspects of Parkinson's disease. CNS Spectr 2006;11(7):541-54. [18] Mayeux R, Stern Y, Rosen J, Leventhal J. Depression, intellectual impairment, and Parkinson's disease. Neurology 1981;31(6): 645-50. [19] Aarsland D, Larsen JP, Tandberg E, Laake K. Predictors of nursing home placement in Parkinson's disease: a population-based, prospective study. J Am Geriatr Soc 2000;48(8):938-42. [20] Gupta A, Bhatia S. Psychological functioning in patients with Parkinson's disease. Parkinsonism Relat Disord 2000;6(3):185-90. [21] Weintraub D, Moberg PJ, Duda JE, Katz IR, Stern MB. Effect of psychiatric and other non-motor symptoms on disability in Parkinson's disease. J Am Geriatr Soc 2004;52(5):784-8. [22] Starkstein SE, Mayberg HS, Leiguarda R, Preziosi TJ, Robinson RG. A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 1992;55(5):377-82. [23] Kuhn W, Heye N, Müller T, Kraus P, Klotz P, Friedrich B, et al. The motor performance test series in Parkinson's disease is influenced by depression. J Neural Transm 1996;103(3):349-54. [24] Papapetropoulos S, Ellul J, Argyriou AA, Chroni E, Lekka NP. The effect of depression on motor function and disease severity of Parkinson's disease. Clin Neurol Neurosurg 2006;108(5):465-9.
A. Piccinni et al. / Comprehensive Psychiatry 53 (2012) 727–731 [25] Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55(3): 181-4. [26] Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;17(5):427-42. [27] Fahn S, Elton RL. Members of the UPDRS Development Committee: Unified Parkinson's disease rating scale. In: Fahn S, Marsden CD, & Calne DB, editors. Recent development in Parkinson's disease. Florham Park: Macmillan Health Care Information; 1987. p. 153-63. [28] First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders Clinician Version (SCID-CV). Washington, DC: American Psychiatric Press; 1997. [29] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text-Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.
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[30] Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62. [31] Guy W. ECDEU assessment manual for psychopharmacology. Rev. Rockville, MD: National Institute of Health, Psychopharmacology Research Branch; 1976. [32] Naarding P, Leentjens AF, van Kooten F, Verhey FR. Disease-specific properties of the Rating Scale for Depression in patients with stroke, Alzheimer's dementia, and Parkinson's disease. J Neuropsychiatry Clin Neurosci 2002;14(3):329-34. [33] Marsh L. Neuropsychiatric aspects of Parkinson's disease. Psychosomatics 2000;41(1):15-23. [34] Poewe W, Luginger E. Depression in Parkinson's disease: impediments to recognition and treatment options. Neurology 1999;52(7 Suppl 3):S2-6. [35] Oertel WH, Höglinger GU, Caraceni T, Girotti F, Eichhorn T, Spottke AE, et al. Depression in Parkinson's disease. An update. Adv Neurol 2001;86:373-83.
Comprehensive Psychiatry 53 (2012) 727 – 731 www.elsevier.com/locate/comppsych
Depressive symptoms in Parkinson's disease Armando Piccinni a , Donatella Marazziti a , Antonello Veltri a,⁎, Roberto Ceravolo b , Carla Ramacciotti a , Marina Carlini a , Alessandro Del Debbio a , Elisa Schiavi a , Ubaldo Bonuccelli b , Liliana Dell'Osso a a
Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Via Roma 67, 56126 Pisa, Italy b Department of Neuroscience, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy
Abstract Objective: We aimed to investigate the relationship between the presence and severity of depression and the degree of motor and functional disability in Parkinson's disease (PD). Methods: One hundred twenty-two outpatients with PD were enrolled in a neurology department: 65 satisfied the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria for major depression, and 57 did not (PD-C). Depressive symptoms were assessed by means of the Hamilton Rating Scale for Depression (HRSD), and the PD severity was assessed according to the Hoehn and Yahr System. Activities of daily living and motor symptoms were measured by the Unified PD Rating Scale (UPDRS), parts II and III. Results: Twenty-nine patients had a mild depression (HRSD total score ranging between 8 and 17), 30 had a moderate depression (HRSD total score ranging between 18 and 24), and 6 had a severe depression (HRSD total score, ≥25). By comparing the 3 groups of patients, it emerged that those with a severe depression showed significantly higher scores at the UPDRS II, UPDRS III, and HY scales than did PD-C or patients with a mild depression. Moreover, patients with a moderate depression scored significantly higher on the UPDRS II, UPDRS III, and HY scales than did PD-C or those with a mild depression. Conclusions: Our findings suggest that depression and motor symptoms/well-being are highly intertwined in patients with PD. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Parkinson's disease (PD) is a neurodegenerative disorder characterized by bradykinesia, rigidity, and rest tremor [1]. Depressive disorders may affect between 2.7% and 90% of patients with PD and are associated with increased disability and reduced quality of life, although they are often underestimated [2-9]. Risk factors associated with depression include also a longer PD duration and a greater impairment in daily activities [10]. The investigation of depression in PD is complicated by a certain degree of overlap between
⁎ Corresponding author. Tel.: +39 050 992642; fax: +39 050 992925. E-mail addresses: [email protected] (A. Piccinni), [email protected] (D. Marazziti), [email protected] (A. Veltri), [email protected] (R. Ceravolo), [email protected] (A. Del Debbio), [email protected] (E. Schiavi), [email protected] (U. Bonuccelli), [email protected] (L. Dell'Osso). 0010-440X/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.comppsych.2011.11.002
the 2 symptom patterns: psychomotor retardation or agitation, hypomimia, fatigue, or loss of appetite. An increasing number of evidence suggests that depression in PD might be secondary to the underlying neuroanatomical degeneration, rather than a simple reaction to the psychosocial stress and disability [11]. Parkinson's disease is, in fact, characterized by degeneration of the subcortical nuclei, such as the ventral tegmental area, hypothalamus, dorsal raphe, and locus coeruleus; and some of these have been implicated also in the pathophysiology of depression [12,13]. A decreased density of serotonin neurons in the dorsal raphe and of dopamine neurons in the ventral tegmental area is a common finding detected in postmortem brain specimens of patients with PD with a history of depression [12,13]. The different degree of degeneration of subcortical structures has been linked to the clinical heterogeneity of the non-motor syndromes of PD, in particular, to depression, psychosis, and even dementia [12,14]. The correlation of depressive symptoms with specific clinical features of PD has been demonstrated as well: patients with right-sided motor symptoms and with the
728
A. Piccinni et al. / Comprehensive Psychiatry 53 (2012) 727–731
akinetic rigid type of PD show a higher comorbidity with depression, if compared with the classic type of PD (tremor, rigidity, and/or bradykinesia) [15,16]. Some studies suggest that non-motor symptoms such as autonomic disorders and depression are important factors influencing the quality of life of patients with PD [5,17]. In particular, it has been proposed that a consistent degree of physical disability in PD is associated with depression, but opposite findings are also available [18-21]. Depression may provoke a greater impairment of fine-motor skills, and subsequently, it would increase the disability associated with a given level of motor manifestations [22-24]. The aim of the present study was to explore how different degrees of depressive symptoms, as assessed by the Hamilton Rating Scale for Depression (HRSD), may contribute to an increased disability in patients with PD. 2. Methods 2.1. Patients A sample of 122 patients with idiopathic PD was consecutively recruited at the Movement Disorders Unit of the Department of Neuroscience of the Pisa University (Italy). Diagnosis of idiopathic PD was made in agreement with the UK PD Society Brain Bank clinical criteria for PD [25]. There was no age limit for inclusion in the study. Patients with other parkinsonian syndromes, or presenting cognitive deterioration, as evaluated by the Mini Mental State Examination (b23), or a positive history for drug-induced psychosis, brain tumors, cerebrovascular accidents, late outcomes of brain injuries, epilepsy, or pregnancy were excluded. All patients were given full information about the protocol and gave written informed consent to the study, which was approved by the local ethics committee. 2.2. Assessment The patients were assessed by a neurologist (R.C.) by means of the Unified PD Rating Scale (UPDRS) and were staged according to the Hoehn and Yahr System (H/Y) [26,27]. The UPDRS is the criterion standard of motor measurement in PD and has proven highly effective in clinical management and research [27]. It consists of 4 parts: I, mentation, behavior, and mood; II, activities of daily living (ADL); III, motor examination; and IV, complications of therapy. For the purpose of our study, we used sections II and III of UPDRS. The H/Y scale measures the severity of the disease and is based on lateralization of the symptoms and balance evaluation. Higher scores on both scales indicate a more severe impairment. Other clinical features such as akinetic-rigid vs tremor-dominant form, instability, dyskinesias, “on-off” periods, PD duration, and antiparkinsonian treatment were also collected. All patients underwent a psychiatric evaluation performed by a psychiatrist (A.P.), and current and lifetime diagnoses were carried out according to the Diagnostic and Statistical Manual of Mental
Disorder, Fourth Edition, Text Revision (DSM-IV-TR) criteria by the Structured Clinical Interview for DSM [28,29]. The 21-item HRSD was used for symptom assessment [30]. The HRSD is the most widely used and accepted measure for evaluating the severity of depression [31]; in particular, in patients with PD, it shows good sensitivity and specificity [32]. The HRSD total score between 8 and 17 identifies a mild depression; between 18 and 24, a moderate depression; and ≥25, a severe depression. 2.3. Statistical analyses Because data were not normally distributed, as shown by the Kolmogorov-Smirnov test, non-parametric tests were used. The Kruskal-Wallis test (KW) with post-hoc pair-wise Mann-Whitney multiple comparisons and χ 2 test were used to compare continuous and categorical variables across groups, respectively. A P value less than .05 was considered significant. Statistical analyses were performed by means of the Statistical Package for Social Science (version 12.5; SPSS, Chicago, IL). 3. Results Seventy patients were men, and 52 were women (mean ± SD age, 67.01 ± 8.54 years); the disease duration (mean ± SD) was 6.90 ± 4.80 years. Eighty-seven patients were nonfluctuating, and 35 had on-off phenomena. One hundred twelve patients were treated with L-dopa or dopamine agonists, whereas 10 were drug-free. With regard to the types of dopaminergic treatment, the sample could be divided into 3 subgroups: 56 patients (50%) were taking L-dopa and dopamine agonists (21 were taking pergolide; 19, ropinirole; and 16, pramipexole); 45 (40.2%), L-dopa alone; and 11 (9.8%), dopamine agonists alone (4 were taking ropinirole; 4, pergolide; and 3, pramipexole). No patient was receiving deep brain stimulation. Sixty-five patients (52.2%) of the total of 122 satisfied the DSM-IV criteria for current major depression: 29 (44.6%) had a mild depression, 30 (46.1%) had a moderate depression, and 6 (9.3%) had a severe depression (Table 1). Besides the current episode, 5 patients had a positive history of lifetime depression, as assessed by the Structured Clinical Interview for DSM. Patients with and without depression were similar in terms of age, sex, and duration of illness. On the contrary, the UPDRS II (KW: z = 8.2, P = .041), UPDRS III (KW: z = 12.0, P = .007), and H/Y (KW: z = 9.8, P = .020) scores were significantly higher in depressed than in non-depressed patients. The same was true for tremor (χ 2: z = 22.8, P = .029), instability (χ 2: z = 22.8, P = .030), or dyskinesias (χ 2: z = 27.6, P = .006) and duration of L-dopa treatment (KW: z = 7.7, P = .000) (Table 2). The post-hoc analyses showed that patients with severe depression had significantly higher scores on the UPDRS II, UPDRS III, and H/Y scales compared with those with mild or without depression. Moreover, patients with moderate
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Table 1 Demographic characteristics of 122 PD patients with (PD-D) and without (PD-C) depression HRSD total score PD-D (n = 65)
Sex Female Male Age (y) Duration of PD (mo)
F
P
2.64
.451
1.9 2.2
.130 .089
PD-C (n = 57)
8-17, mild depression (n = 29)
18-24, moderate depression (n = 30)
≥25, severe depression (n = 6)
15 (51.7%) 14 (48.3%) 65.4 ± 6.8 5.4 ± 4.8
14 (46.7%) 16 (53.3%) 66.9 ± 8.0 8.5 ± 5.7
3 (50%) 3 (50%) 74.5 ± 6.3 7.6 ± 1.7
depression scored significantly higher on the UPDRS III and H/Y than mildly depressed or nondepressed patients.
4. Discussion The purpose of this study was to assess the possible impact of depression, as well as of its severity, on physical disability and functioning in a cohort of patients with PD. The results showed that about 53% (n = 65) of patients with PD were experiencing a clinically relevant depression. This is consistent with some previous findings, although it should be underlined that the prevalence rates of depression range widely between 2.7% and 90%, according to different studies [8,33]. The nature of the population studied, the heterogeneity of diagnostic criteria, the different assessment techniques, the statistical analyses used, and the type of depressive disorders may explain this wide variation [10]. In our study, by using the HRSD cut-off scores of 8 to 17, 18 to 24, and 25 or greater for depression severity, 23.8% of
20 (35.1%) 37 (64.9%) 67.1 ± 9.5 6.7 ± 4.2
patients with PD had a mild depression, 24.6% had a moderate depression, and 4.9% had a severe depression. In addition, those patients with depressive symptoms ranging between mild and severe, scored higher on different measures of PD severity and functioning in daily living than did non-depressed patients: the higher the depressive score, the higher the physical and functioning impairments. Furthermore, the most patients with severe depression reported the worst outcome on the UPDRS II, UPDRS III, and H/Y scales. The available data on the association between depression and PD severity are conflicting, with most of them reporting a positive association and some reporting no correlation [15,34,35]. The results of the current study are consistent with those showing that a diagnosis of depression was related to higher scores on the UPDRS II (ADL) and UPDRS III (motor examination) [21,24]. However, to our knowledge, the present study is the first to examine the effect of depressive symptom severity on physical disability and functioning by subtyping depressed patients with PD
Table 2 Comparisons of PD patients with (PD-D) and without (PD-C) depression HRSD total score PD-D (n = 65)
Scores on clinical measures UPDRS II UPDRS III MMSE H/Y scale Tremor Rigidity Instability On-off phenomena Dyskinesias L-Dopa treatment Duration of L-Dopa treatment (mo)
F
P
8.2 12.0 1.8 9.8 22.8 14.25 22.79 19.43 27.59 6.24 7.75
.041 .007 .152 .020 .029 .114 .030 .079 .006 .100 .000
PD-C (n = 57)
8-17, mild depression (n = 29)
18-24, moderate depression (n = 30)
≥25, severe depression (n = 6)
12.8 ± 4.2 16.1 ± 5.9 27.8 ± 1.9 1.4 ± 0.6 22 (75.8%) 22 (75.8%) 14 (48.2%) 5 (17.2%) 4 (13.8%) 20 (61.4%) 49.5 ± 56.2
14.6 ± 4.9 21.7 ± 10.0 27.5 ± 1.9 1.8 ± 0.6 21 (70.0%) 22 (73.3%) 20 (66.7%) 12 (40.1%) 14 (46.6%) 28 (93.3%) 99.6 ± 87.4
16.8 ± 2.9 22.3 ± 6.1 25.8 ± 1.9 2.0 ± 0.0 3 (50.0%) 5 (83.4%) 4 (66.7%) 2 (33.3%) 4 (66.7%) 5 (83.3%) 120.2 ± 21.9
12.8 ± 2.9 16.0 ± 4.3 27.3 ± 1.9 1.5 ± 0.6 39 (68.4%) 45 (79.0%) 33 (57.9%) 16 (28.1%) 22 (38.6%) 48 (84.2%) 47.4 ± 34.8
Post-hoc tests: UPDRS II: PD-C b PD-D (severe depression); z = −2.699, P = .007; PD-D (mild depression) b PD-D (severe depression); z = −2.261, P = .025; UPDRS III: PD-C b PD-D (moderate depression); z = −2.073, P = .038; PD-C b PD-D (severe depression); z = −2.655, P = .008; PD-D (mild depression) b PD-D (moderate depression); z = −2.422, P = .015; PD-D (mild depression) b PD-D (severe depression); z = −2.467, P = .014; H/Y scale: PD-C b PD-D (moderate depression); z = −2.064, P = .039; PD-C b PD-D (severe depression); z = −2.038, P = .042; PD-D (mild depression) b PD-D (moderate depression); z = −2.317, P = .021; PD-D (mild depression) b PD-D (severe depression); z = −2.278, P = .023. MMSE indicates Mini Mental State Examination.
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according to the HRSD total score. Our results seem to confirm that severely depressed patients with PD may be significantly more disabled than mildly depressed or nondepressed ones. The characterization of depressive symptoms in PD along a continuum by using the “severity” parameter may, thus, permit to ascertain more accurately the effects of depression on physical status and functioning and, perhaps, may be of help to identify clinical phenotypes of patients with PD with different degrees of disability. In our sample, the depression severity was significantly associated with higher scores on the H/Y scale, a longer duration of L-dopa treatment, and the presence of some specific clinical features of PD, such as tremor, gait instability, and dyskinesias. Generally, depression has been associated with the akinetic rigid type of PD, bradykinesia, and gait instability compared with tremor-dominant forms [15,16]. Our results confirm these findings and show a trend toward a high prevalence of dyskinesias and gait instability in severely and moderately depressed patients. When interpreting these data, several limitations should be acknowledged. First, the sample was restricted to individuals seeking treatment in a neurology department, and this may limit the generalizability of these data. Patients with PD not receiving treatment and those seeking for treatment from other types of specialists may have different profiles. Furthermore, certain confounding factors that potentially could affect health status are not taken into account (ie, severity of other medical conditions, diet, exercise, and other lifestyle factors). Another limitation is the cross-sectional nature of the study, which does not permit to establish whether physical and functional impairment may affect depression or vice versa. Again, the number of patients with different severity of depression was not similar; in particular, the patients with the most severe symptoms were only 6, and this might impair the statistical analyses. Furthermore, for the small sample size, we could not compare patients with only current vs those with current and lifetime depression. Limited bias due to multiple comparisons should also be considered.
4. Conclusion In conclusion, our results confirm the high prevalence of depression in patients with PD. In addition, they support the notion that depression and motor disability or functioning in daily activities are strictly intertwined. Therefore, the presence of depression in patients with PD should be routinely assessed in the clinical practice because it might significantly influence motor symptoms and well-being. References [1] Parkinson J. An essay on the shaking palsy (reprinted from 1817). J Neuropsychiatry Clin Neurosci 2002;14(2):223-36.
[2] Cole SA, Woodard JL, Juncos JL, Kogos JL, Youngstrom EA, Watts RL. Depression and disability in Parkinson's disease. J Neuropsychiatry Clin Neurosci 1996;8(1):20-5. [3] Schrag A, Jahanshahi M, Quinn N. How does Parkinson's disease affect quality of life? A comparison with quality of life in the general population. Mov Disord 2000;15(6):1112-8. [4] Slaughter JR, Slaughter KA, Nichols D, Holmes SE, Martens MP. Prevalence, clinical manifestations, etiology, and treatment of depression in Parkinson's disease. J Neuropsychiatry Clin Neurosci 2001;13(2): 187-96. [5] Yamamoto M. Depression in Parkinson's disease: its prevalence, diagnosis, and neurochemical background. J Neurol 2001;248(Suppl 3):III5-11. [6] Marsh L, McDonald WM, Cummings J, Ravina B, NINDS/NIMH Work Group on Depression and Parkinson's Disease. Provisional diagnostic criteria for depression in Parkinson's disease: report of an NINDS/NIMH Work Group. Mov Disord 2006;21(2):148-58. [7] Ravina B, Camicioli R, Como PG, Marsh L, Jankovic J, Weintraub D, et al. The impact of depressive symptoms in early Parkinson disease. Neurology 2007;69(4):342-7. [8] Reijnders JS, Ehrt U, Weber WE, Aarsland D, Leentjens AF. A systematic review of prevalence studies of depression in Parkinson's disease. Mov Disord 2008;23(2):183-9. [9] Riedel O, Heuser I, Klotsche J, Dodel R, Wittchen HU, GEPAD Study Group. Occurrence risk and structure of depression in Parkinson disease with and without dementia: results from the GEPAD Study. J Geriatr Psychiatry Neurol 2010;23(1):27-34. [10] Jasinska-Myga B, Putzke JD, Wider C, Wszolek ZK, Uitti RJ. Depression in Parkinson's disease. Can J Neurol Sci 2010;37(1): 61-6. [11] McDonald WM, Richard IH, DeLong MR. Prevalence, etiology, and treatment of depression in Parkinson's disease. Biol Psychiatry 2003;54(3):363-75. [12] Paulus W, Jellinger K. The neuropathologic basis of different clinical subgroups of Parkinson's disease. J Neuropathol Exp Neurol 1991; 50(6):743-55. [13] Brown AS, Gershon S. Dopamine and depression. J Neural Transm Gen Sect 1993;91(2-3):75-109. [14] Jellinger KA, Paulus W. Clinico-pathological correlations in Parkinson's disease. Clin Neurol Neurosurg 1992;94(Suppl):S86-8. [15] Cummings JL. Depression and Parkinson's disease: a review. Am J Psychiatry 1992;149(4):443-54. [16] Starkstein SE, Preziosi TJ, Bolduc PL, Robinson RG. Depression in Parkinson's disease. J Nerv Ment Dis 1990;178(1):27-31. [17] Borek LL, Amick MM, Friedman JH. Non-motor aspects of Parkinson's disease. CNS Spectr 2006;11(7):541-54. [18] Mayeux R, Stern Y, Rosen J, Leventhal J. Depression, intellectual impairment, and Parkinson's disease. Neurology 1981;31(6): 645-50. [19] Aarsland D, Larsen JP, Tandberg E, Laake K. Predictors of nursing home placement in Parkinson's disease: a population-based, prospective study. J Am Geriatr Soc 2000;48(8):938-42. [20] Gupta A, Bhatia S. Psychological functioning in patients with Parkinson's disease. Parkinsonism Relat Disord 2000;6(3):185-90. [21] Weintraub D, Moberg PJ, Duda JE, Katz IR, Stern MB. Effect of psychiatric and other non-motor symptoms on disability in Parkinson's disease. J Am Geriatr Soc 2004;52(5):784-8. [22] Starkstein SE, Mayberg HS, Leiguarda R, Preziosi TJ, Robinson RG. A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 1992;55(5):377-82. [23] Kuhn W, Heye N, Müller T, Kraus P, Klotz P, Friedrich B, et al. The motor performance test series in Parkinson's disease is influenced by depression. J Neural Transm 1996;103(3):349-54. [24] Papapetropoulos S, Ellul J, Argyriou AA, Chroni E, Lekka NP. The effect of depression on motor function and disease severity of Parkinson's disease. Clin Neurol Neurosurg 2006;108(5):465-9.
A. Piccinni et al. / Comprehensive Psychiatry 53 (2012) 727–731 [25] Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55(3): 181-4. [26] Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;17(5):427-42. [27] Fahn S, Elton RL. Members of the UPDRS Development Committee: Unified Parkinson's disease rating scale. In: Fahn S, Marsden CD, & Calne DB, editors. Recent development in Parkinson's disease. Florham Park: Macmillan Health Care Information; 1987. p. 153-63. [28] First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders Clinician Version (SCID-CV). Washington, DC: American Psychiatric Press; 1997. [29] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text-Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.
731
[30] Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62. [31] Guy W. ECDEU assessment manual for psychopharmacology. Rev. Rockville, MD: National Institute of Health, Psychopharmacology Research Branch; 1976. [32] Naarding P, Leentjens AF, van Kooten F, Verhey FR. Disease-specific properties of the Rating Scale for Depression in patients with stroke, Alzheimer's dementia, and Parkinson's disease. J Neuropsychiatry Clin Neurosci 2002;14(3):329-34. [33] Marsh L. Neuropsychiatric aspects of Parkinson's disease. Psychosomatics 2000;41(1):15-23. [34] Poewe W, Luginger E. Depression in Parkinson's disease: impediments to recognition and treatment options. Neurology 1999;52(7 Suppl 3):S2-6. [35] Oertel WH, Höglinger GU, Caraceni T, Girotti F, Eichhorn T, Spottke AE, et al. Depression in Parkinson's disease. An update. Adv Neurol 2001;86:373-83.