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Depressive symptoms and the dexamethasone suppression test in parkinsonian patients
386
BIOL
PSYCHIATRY
1987:22:386389
BRIEF REPORTS
Depressive Symptoms and the Dexamethasone Suppression Test in Parkinsonian Patients M. Luiz Frochtengarten, Jo50 C. B. Villares, Eliana Maluf, and E. A. Carlini
Introduction
Methods
Among the various symptoms and signs presented by parkinsonian patients, depression has been variously reported in from 20% to 90% of these patients (Warburton 1967; Brown and Wilson 1972; Asnis 1977; Mayeux et al. 1981, 1984; Guillard and Fenelon 1983). Sometimes, depression may present itself as the initial symptom of a parkinsonian syndrome, causing a delay in diagnosis of the underlying disease (Guillard and Fenelon 1983). Some authors ascribe this depression to disturbed neurotransmitter mechanisms, others believe the depression is an independent psychic reaction to a severely incapacitating disease. These uncertainties stimulated our interest in studying the Dexamethasone Suppression Test (DST) in parkinsonian patients, as this test is said to correlate meaningfully with endogenous depression (Carroll et al. 1981; Green and Kane 1983; Carroll 1986).
Fifty-six patients (27 men and 29 women) with Parkinson’s disease and no other medical condition volunteered to participate in this study. They were attending an outpatient clinic for movement disorders and were randomly selected. Their mean age was 63 years (range 37-82); average disease duration was 5.4 years. The control group consisted of 27 healthy volunteers, 14 of them being over 40 years of age. A group of 7 hospitalized depressive patients [diagnosed as major depression by Research Diagnostic Criteria (RDC)] also were given the DST for control purposes. The parkinsonian patients were rated on the Hoehn and Yahr Scale (HYS) for motor disabilities (Hoehn and Yahr 1967) and by a modified Hamilton Rating Scale for Depression (HRSD) (Hamilton 1960). From the original HRSD with 17 items, those concerning work and interests (item 7), agitation (item 9), and general somatic symptoms (item 13) were excluded because of the disability of the patients; item 16 (insight) was also excluded, as parkinsonian patients have a clear recognition of their own disease. Therefore, the maximum score for the remaining 13 items was reduced to 40 points instead of the original 50. Patients scoring 9 or more points were considered to have significant depressive symptoms. DST was performed according to the method described by Carroll et al. (1981). Dexameth-
From the Department cina. S&o Paula,
of Psychobiology,
Escola Paulista
Address reprint requests to Dr. M. Luiz Fmchtenganen. of Psychobiology, 862,04@23
Escola Paulista de Medicina,
Sio Paul-z-SP,
Brazil.
Supported in part by FINEP and AFIP. Received April 4. 1986; revised August
0
1987 Society
de Medi-
Brazil.
of Biological
Psychiatry
13. 1986.
Department
Rua Botucatu,
oGlI6-3223/87/$03
SO
BIOL PSYCHIATRY 1987:22:386-389
Brief Reports
asone (1 mg) was administered orally at 11:OO PM and blood was drawn at 4:00 PM on the next day. Cortisol was assayed by radioimmunoassay using kits supplied by Diagnostic Products Corporation, Los Angeles, CA. Nonsuppression was defined as a plasma cortisol 24 pg/dl in the postdexamethasone sample (see Results). The inter- and intraassay coefficients of variation were 3.79% and 9.70%, respectively.
Results According to HYS, 2 patients scored degree I, 11 scored degree II, 42 attained degree III, and only one degree IV (see Figure 1). Patients were also subdivided into two categories, “depressed” and “not depressed,” according to the HRSD, with 9 as the cut-off point (Figure 1): 35 patients (62.5%) were “depressed” (13 men and 22 women) and 21 (37.5%) were “not depressed” (14 men and 7 women). A positive correlation of 0.51 by the Spearman test was found between the degree of depression and the degree of functional incapacity (p < 0.001). Only one of the 27 normal volunteers (3.7%; specificity 96%) was a nonsuppressor. Other Brazilian authors (Dratcu and Calil, unpublished results) found 1 nonsuppressor in 40 healthy
387
volunteers (2.5%; specificity 97%). Four of our 7 hospitalized patients with a diagnosis of major depression by RDC were nonsuppressors (sensitivity of 57%). In another group of 18 Brazilian major depressive hospitalized patients (RDC), the sensitivity was 56% (Dratcu and Calil, unpublished results). From the total of 56 parkinsonian patients, only 5 (8.9%, 2 men and 3 women) had abnormal (nonsuppression) responses to DST. Table 1 shows the distribution of patients according to treatment, the percent of “depression” in each treatment group, and the scores on HRSD and HYS. The HYS rating was the same for all treatment groups, but the percent of depressives and the rating in HRSD were lower in the group treated with anticholinergic drugs; however, the difference from other treatment groups was not statistically significant. The 13 patients treated with anticholinergic drugs did not differ from the total 56 patients with regard to median age (69 years) or duration of disease (2 years). The five nonsuppressor patients were quite varied with regard to treatment: one was receiving no drugs, two were receiving anticholinergic drugs plus L-dopa (plus AAAI), and two were on anticholinergics plus tricylic antide-
20 8 w
a I
I
5:
$ d r s
n
n 0
n
0
8 8
10
mm
Scale and their responses to the Dexamethasone Suppression Test. (D) Suppressors; (0) nonsuppressors.
ma a n
8 mm lm n
1
2 HOEHN
m
I
mm mm l
3 AND YAHR
Figure 1. Distribution of 56 parkinsonian patients accordingto their scores on the Hamilton RatingScale for Depressionand Ho&n and Yahr
4 SCALE
BIOL PSYCHIATRY
388
Brief Reports
1987:22:3X&389
Table 1. Distribution of Parkinsonian Patients According to the Various Treatment Groups and Median Score Values in Hamilton Rating Scale and in the Hoehn and Yahr Scale
Treatment
Number of Patients
“Depressed”
Percent “depressed” in the group
HRDS (median)
HYS (median)
Not treated Anticholinergic L-dopa (plus AAAI)
IO I.? 6
I 5 4
70.0 38.5 66.7
II 6 11.5
111 III III
Antichol + L-dopa (plus AAAI)
?I
1.5
71.4
I0
III
4
66.7
Il.5
111
Other associations
6
pressants. Four rated degree III in HYS and one rated degree II. All five patients scored 11 or more points in HRSD.
Discussion Our data indicated a positive correlation between scoring in HRSD and rating in HYS, thus revealing, irrespective of causal inferences, that intensity of depressive symptoms parallels the degree of functional incapacity. Incidence of nonsuppressive patients in the total group (8.9%) did not differ significantly from the normal control group nor from literature reports on normal populations (Carroll et al. 1981). On the other hand, literature data reveal nonsuppressive responses in endogenous depressive patients to be as high as 67% (Carroll et al. 1981). The value found by us was 56%. It is relevant that specific depressive disorders were not diagnosed in the parkinsonian patients; we merely scored symptoms through the HRSD. According to Carroll (1986), the sensitivity of DST is better in patients who “are perhaps best considered melancholic in the historical Kraepelinian sense of the term.” One might thus conclude that our parkinsonian population should not be considered truly melancholic . It could be argued that the low incidence of nonsuppressive cases might be explained by the use of antiparkinsonian drugs. Experimental studies indicated that t.-dopa can, under certain circumstances, diminish adrenocorticotrophin hormone (ACTH) and cortisol secretions (van
Loon et al. 1971); acetylcholine causes a dosedependent release of corticotrophin-releasing hormone, and anticholinergic drugs antagonize this effect (Hillhouse et al. 1975); a single oral dose of bromocriptine elicits a significant reduction of plasma ACTH and cortisol levels in patients with untreated Cushing’s disease (Lamberts et al. 1980; Adams et al. 1981). Nevertheless, the five nonsuppressor patients were randomly distributed, irrespective of the kind of drug they were using. Furthermore, only 1 of the 10 nonmedicated patients was a nonsuppressor. It thus seems that DST is not useful for the further characterization of depressive symptoms in Parkinson’s disease.
References Adams EF, Ashby MJ, Brown SM, hnite MC, Mashiter K (1981): Bromocriptine suppresses ACTH secretion from human pituitary tumour cells in culture by a dopaminergic mechanism. Clin Endocrinol 15:479484. Asnis G (1977): Parkinson’s disease, depression and ECT: A review and case study. Am J Psychiatry 134:191-195. Brown GL, Wilson WP (1972): Parkinsonism depression. South Med J 65:54@-545.
and
Carroll BJ (1986): Informed use of the Dexamethasone Suppression Test. J Clin Psychiatry (Suppl) 47:10-12. Carroll BJ, Feinberg M, Greden JR, Tarika J, Albala AA, Haakett RF, James NM, Kronfol Z, Lohr N, Steiner M, de Vigne JP, Young E (1981): A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility. Arch Gen Psychiatry 38: 15-22.
BIOL PSYCHIATRY 1987:22:386389
Brief Reports
Green HS, Kane JM (1983): The Dexamethasone SuppressionTest in depression. Clin Neuropharmacol6:7-24.
Guillard A, Fenelon G (1983): Maladie de Parkinson et syndromes parkinsoniens. Encycl Med Chir Paris Neurol 17062 A’O. Hamilton M (1960): A rating scale for depression. J Neurol Neurosurg Psychiatry 231X-62.
Hillhouse EW, Burden J, Jones MT (1975): The effect of various putative neurotransmitters on the release of corticotrophin releasing hormone from the hypothalamus of the rat in vitro. I. The effect of acetylcholine and noradrenaline. Neuroendocrimlogy 17:1-11. Hoehn MM, Yahr MD (1967): Parkinsonism: Onset, progression, and mortality. Neurology 17:427-442. Lamberts SWJ, Klijn JGM, de Quijada M, Timmermans HAT, Uitterlinden P, de Jong FH, Birkenhager JC (1980): The mechanism of the suppres-
389
sive action of bromoctiptine on adrenocorticotrophin secretion in patients with Cushing’s disease and Nelson’s syndrome. J Clin Enabcrinol Metab 51:307-311.
Mayeux R, Stem Y, Rosen J, Leventhal J (1981): Depression, intellectual impairment, and Parkinson’s disease. Neurology 31:645-650. Mayeux R, Stem Y, Cote L, Williams JBW (1984): Altered serotonin metabolism in depressed patients with Parkinson’s disease. Neurology 34fS42-646. van Loon GR, Hilger L, King AB, Boryczka AT,
Ganon WF (1971): Inhibitory effect of rdihydroxyphenylalanine on the adrenal venous 17-hydroxycorticosteroid response to surgical stress in dogs. Endocrinology 88:1404-1414. Warburton JW (1967): Depressive symptoms in Parkinson patients referred for thalamotomy. J Neurol Neurosurg Psychiatry 30~368-370.
The Influence of Daytime Naps on the Therapeutic Effect of Sleep Deprivation Michael Wiegand, Mathias Berger, Jiirgen Zulley, Christoph Lauer, and Detlev von Zerssen
Introduction The antidepressant effect of total sleep deprivation has been noted by several observers (Gerner et al. 1979; Gillin 1983). It has also been reported that in some cases, even a short nap on the day following sleep deprivation can provoke a mood setback, or even a marked exac-
FKXII the Max-Pbck-Institute of Psychiatry. Munich, F.R.G. Addtess reprint quests to Dr. M. Wiegand, Max-Planck-Institute of Psychiatry, Kmepdinstr. 10, D-8000 M~~I&XI 40, F.R.G. Reccid May 27, 1986; revised August 18, 1986.
0 1987 Society of Biological
Psychiatry
erbation of depression in patients who had improved (FVlug and Tolle 1971; PlIug 1972; Knowles et al. 1979; Roy-Byrne et al. 1984). These anecdotal accounts, however, have thus far not been systematically repeated in an experimental manner. Beyond its clinical importance, the possible reversal of the benefits of sleep deprivation by a short nap carries some interesting theoretical implications. Stated simply, the depressiogenic sleep theory declares that sleep may induce depression and that sleep deprivation relieves it. The additional hypothesis has been advanced
OOQ6-3223/87/$03,50
BIOL
PSYCHIATRY
1987:22:386389
BRIEF REPORTS
Depressive Symptoms and the Dexamethasone Suppression Test in Parkinsonian Patients M. Luiz Frochtengarten, Jo50 C. B. Villares, Eliana Maluf, and E. A. Carlini
Introduction
Methods
Among the various symptoms and signs presented by parkinsonian patients, depression has been variously reported in from 20% to 90% of these patients (Warburton 1967; Brown and Wilson 1972; Asnis 1977; Mayeux et al. 1981, 1984; Guillard and Fenelon 1983). Sometimes, depression may present itself as the initial symptom of a parkinsonian syndrome, causing a delay in diagnosis of the underlying disease (Guillard and Fenelon 1983). Some authors ascribe this depression to disturbed neurotransmitter mechanisms, others believe the depression is an independent psychic reaction to a severely incapacitating disease. These uncertainties stimulated our interest in studying the Dexamethasone Suppression Test (DST) in parkinsonian patients, as this test is said to correlate meaningfully with endogenous depression (Carroll et al. 1981; Green and Kane 1983; Carroll 1986).
Fifty-six patients (27 men and 29 women) with Parkinson’s disease and no other medical condition volunteered to participate in this study. They were attending an outpatient clinic for movement disorders and were randomly selected. Their mean age was 63 years (range 37-82); average disease duration was 5.4 years. The control group consisted of 27 healthy volunteers, 14 of them being over 40 years of age. A group of 7 hospitalized depressive patients [diagnosed as major depression by Research Diagnostic Criteria (RDC)] also were given the DST for control purposes. The parkinsonian patients were rated on the Hoehn and Yahr Scale (HYS) for motor disabilities (Hoehn and Yahr 1967) and by a modified Hamilton Rating Scale for Depression (HRSD) (Hamilton 1960). From the original HRSD with 17 items, those concerning work and interests (item 7), agitation (item 9), and general somatic symptoms (item 13) were excluded because of the disability of the patients; item 16 (insight) was also excluded, as parkinsonian patients have a clear recognition of their own disease. Therefore, the maximum score for the remaining 13 items was reduced to 40 points instead of the original 50. Patients scoring 9 or more points were considered to have significant depressive symptoms. DST was performed according to the method described by Carroll et al. (1981). Dexameth-
From the Department cina. S&o Paula,
of Psychobiology,
Escola Paulista
Address reprint requests to Dr. M. Luiz Fmchtenganen. of Psychobiology, 862,04@23
Escola Paulista de Medicina,
Sio Paul-z-SP,
Brazil.
Supported in part by FINEP and AFIP. Received April 4. 1986; revised August
0
1987 Society
de Medi-
Brazil.
of Biological
Psychiatry
13. 1986.
Department
Rua Botucatu,
oGlI6-3223/87/$03
SO
BIOL PSYCHIATRY 1987:22:386-389
Brief Reports
asone (1 mg) was administered orally at 11:OO PM and blood was drawn at 4:00 PM on the next day. Cortisol was assayed by radioimmunoassay using kits supplied by Diagnostic Products Corporation, Los Angeles, CA. Nonsuppression was defined as a plasma cortisol 24 pg/dl in the postdexamethasone sample (see Results). The inter- and intraassay coefficients of variation were 3.79% and 9.70%, respectively.
Results According to HYS, 2 patients scored degree I, 11 scored degree II, 42 attained degree III, and only one degree IV (see Figure 1). Patients were also subdivided into two categories, “depressed” and “not depressed,” according to the HRSD, with 9 as the cut-off point (Figure 1): 35 patients (62.5%) were “depressed” (13 men and 22 women) and 21 (37.5%) were “not depressed” (14 men and 7 women). A positive correlation of 0.51 by the Spearman test was found between the degree of depression and the degree of functional incapacity (p < 0.001). Only one of the 27 normal volunteers (3.7%; specificity 96%) was a nonsuppressor. Other Brazilian authors (Dratcu and Calil, unpublished results) found 1 nonsuppressor in 40 healthy
387
volunteers (2.5%; specificity 97%). Four of our 7 hospitalized patients with a diagnosis of major depression by RDC were nonsuppressors (sensitivity of 57%). In another group of 18 Brazilian major depressive hospitalized patients (RDC), the sensitivity was 56% (Dratcu and Calil, unpublished results). From the total of 56 parkinsonian patients, only 5 (8.9%, 2 men and 3 women) had abnormal (nonsuppression) responses to DST. Table 1 shows the distribution of patients according to treatment, the percent of “depression” in each treatment group, and the scores on HRSD and HYS. The HYS rating was the same for all treatment groups, but the percent of depressives and the rating in HRSD were lower in the group treated with anticholinergic drugs; however, the difference from other treatment groups was not statistically significant. The 13 patients treated with anticholinergic drugs did not differ from the total 56 patients with regard to median age (69 years) or duration of disease (2 years). The five nonsuppressor patients were quite varied with regard to treatment: one was receiving no drugs, two were receiving anticholinergic drugs plus L-dopa (plus AAAI), and two were on anticholinergics plus tricylic antide-
20 8 w
a I
I
5:
$ d r s
n
n 0
n
0
8 8
10
mm
Scale and their responses to the Dexamethasone Suppression Test. (D) Suppressors; (0) nonsuppressors.
ma a n
8 mm lm n
1
2 HOEHN
m
I
mm mm l
3 AND YAHR
Figure 1. Distribution of 56 parkinsonian patients accordingto their scores on the Hamilton RatingScale for Depressionand Ho&n and Yahr
4 SCALE
BIOL PSYCHIATRY
388
Brief Reports
1987:22:3X&389
Table 1. Distribution of Parkinsonian Patients According to the Various Treatment Groups and Median Score Values in Hamilton Rating Scale and in the Hoehn and Yahr Scale
Treatment
Number of Patients
“Depressed”
Percent “depressed” in the group
HRDS (median)
HYS (median)
Not treated Anticholinergic L-dopa (plus AAAI)
IO I.? 6
I 5 4
70.0 38.5 66.7
II 6 11.5
111 III III
Antichol + L-dopa (plus AAAI)
?I
1.5
71.4
I0
III
4
66.7
Il.5
111
Other associations
6
pressants. Four rated degree III in HYS and one rated degree II. All five patients scored 11 or more points in HRSD.
Discussion Our data indicated a positive correlation between scoring in HRSD and rating in HYS, thus revealing, irrespective of causal inferences, that intensity of depressive symptoms parallels the degree of functional incapacity. Incidence of nonsuppressive patients in the total group (8.9%) did not differ significantly from the normal control group nor from literature reports on normal populations (Carroll et al. 1981). On the other hand, literature data reveal nonsuppressive responses in endogenous depressive patients to be as high as 67% (Carroll et al. 1981). The value found by us was 56%. It is relevant that specific depressive disorders were not diagnosed in the parkinsonian patients; we merely scored symptoms through the HRSD. According to Carroll (1986), the sensitivity of DST is better in patients who “are perhaps best considered melancholic in the historical Kraepelinian sense of the term.” One might thus conclude that our parkinsonian population should not be considered truly melancholic . It could be argued that the low incidence of nonsuppressive cases might be explained by the use of antiparkinsonian drugs. Experimental studies indicated that t.-dopa can, under certain circumstances, diminish adrenocorticotrophin hormone (ACTH) and cortisol secretions (van
Loon et al. 1971); acetylcholine causes a dosedependent release of corticotrophin-releasing hormone, and anticholinergic drugs antagonize this effect (Hillhouse et al. 1975); a single oral dose of bromocriptine elicits a significant reduction of plasma ACTH and cortisol levels in patients with untreated Cushing’s disease (Lamberts et al. 1980; Adams et al. 1981). Nevertheless, the five nonsuppressor patients were randomly distributed, irrespective of the kind of drug they were using. Furthermore, only 1 of the 10 nonmedicated patients was a nonsuppressor. It thus seems that DST is not useful for the further characterization of depressive symptoms in Parkinson’s disease.
References Adams EF, Ashby MJ, Brown SM, hnite MC, Mashiter K (1981): Bromocriptine suppresses ACTH secretion from human pituitary tumour cells in culture by a dopaminergic mechanism. Clin Endocrinol 15:479484. Asnis G (1977): Parkinson’s disease, depression and ECT: A review and case study. Am J Psychiatry 134:191-195. Brown GL, Wilson WP (1972): Parkinsonism depression. South Med J 65:54@-545.
and
Carroll BJ (1986): Informed use of the Dexamethasone Suppression Test. J Clin Psychiatry (Suppl) 47:10-12. Carroll BJ, Feinberg M, Greden JR, Tarika J, Albala AA, Haakett RF, James NM, Kronfol Z, Lohr N, Steiner M, de Vigne JP, Young E (1981): A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility. Arch Gen Psychiatry 38: 15-22.
BIOL PSYCHIATRY 1987:22:386389
Brief Reports
Green HS, Kane JM (1983): The Dexamethasone SuppressionTest in depression. Clin Neuropharmacol6:7-24.
Guillard A, Fenelon G (1983): Maladie de Parkinson et syndromes parkinsoniens. Encycl Med Chir Paris Neurol 17062 A’O. Hamilton M (1960): A rating scale for depression. J Neurol Neurosurg Psychiatry 231X-62.
Hillhouse EW, Burden J, Jones MT (1975): The effect of various putative neurotransmitters on the release of corticotrophin releasing hormone from the hypothalamus of the rat in vitro. I. The effect of acetylcholine and noradrenaline. Neuroendocrimlogy 17:1-11. Hoehn MM, Yahr MD (1967): Parkinsonism: Onset, progression, and mortality. Neurology 17:427-442. Lamberts SWJ, Klijn JGM, de Quijada M, Timmermans HAT, Uitterlinden P, de Jong FH, Birkenhager JC (1980): The mechanism of the suppres-
389
sive action of bromoctiptine on adrenocorticotrophin secretion in patients with Cushing’s disease and Nelson’s syndrome. J Clin Enabcrinol Metab 51:307-311.
Mayeux R, Stem Y, Rosen J, Leventhal J (1981): Depression, intellectual impairment, and Parkinson’s disease. Neurology 31:645-650. Mayeux R, Stem Y, Cote L, Williams JBW (1984): Altered serotonin metabolism in depressed patients with Parkinson’s disease. Neurology 34fS42-646. van Loon GR, Hilger L, King AB, Boryczka AT,
Ganon WF (1971): Inhibitory effect of rdihydroxyphenylalanine on the adrenal venous 17-hydroxycorticosteroid response to surgical stress in dogs. Endocrinology 88:1404-1414. Warburton JW (1967): Depressive symptoms in Parkinson patients referred for thalamotomy. J Neurol Neurosurg Psychiatry 30~368-370.
The Influence of Daytime Naps on the Therapeutic Effect of Sleep Deprivation Michael Wiegand, Mathias Berger, Jiirgen Zulley, Christoph Lauer, and Detlev von Zerssen
Introduction The antidepressant effect of total sleep deprivation has been noted by several observers (Gerner et al. 1979; Gillin 1983). It has also been reported that in some cases, even a short nap on the day following sleep deprivation can provoke a mood setback, or even a marked exac-
FKXII the Max-Pbck-Institute of Psychiatry. Munich, F.R.G. Addtess reprint quests to Dr. M. Wiegand, Max-Planck-Institute of Psychiatry, Kmepdinstr. 10, D-8000 M~~I&XI 40, F.R.G. Reccid May 27, 1986; revised August 18, 1986.
0 1987 Society of Biological
Psychiatry
erbation of depression in patients who had improved (FVlug and Tolle 1971; PlIug 1972; Knowles et al. 1979; Roy-Byrne et al. 1984). These anecdotal accounts, however, have thus far not been systematically repeated in an experimental manner. Beyond its clinical importance, the possible reversal of the benefits of sleep deprivation by a short nap carries some interesting theoretical implications. Stated simply, the depressiogenic sleep theory declares that sleep may induce depression and that sleep deprivation relieves it. The additional hypothesis has been advanced
OOQ6-3223/87/$03,50