Movement Disorders Vol. 5 , No. 1, 1990, pp. 23-26 0 1990 Movement Disorder Society

Dexamethasone Suppression Test in Patients with Parkinson’s Disease Vladimir S. KostiC, Nadeida CoviEkoviC-SterniC, Ljiljana BeslaC-BumbaSireviC, Gordana OciC, Dragan PavloviC, and Milisav NikoliC Clinic for Neurology CCMF, Belgrade, Yugoslavia

Summary: The Dexamethasone Suppression Test (DST), supposed to effectively distinguish between endogenous and nonendogenous depression, was performed in a group of 34 patients with Parkinson’s disease. Abnormal DST results were observed in 50% of the patients. The patients were clinically divided into subgroups of depressed and nondepressed parkinsonians. Abnormal DST results were significantly more frequent in depressed (75%) than in nondepressed parkinsonians (27.7%). Key Words: Dexamethasone suppression test-Parkinson’s disease

PATIENTS AND METHODS

Depressive disorders are noted in almost half the patients suffering from Parkinson’s disease (PD) (13). However, a basic dilemma remains unsolved: whether depression is only a reaction to the progressive physical disabilities associated with PD (4), or it is an intrinsic phenomenon reflecting the neurobiological substrates of the disease (5-7). Although the dichotomy “endogenous-reactive” is probably artificial (8), the solution of the dilemma may have therapeutic implications (9). The search for a valid biologic marker for endogenous depression using endocrine tests has attracted an increasing interest (9). Carroll and colleagues (10) found a strong association between the frequency of an abnormal dexamethasone suppression test (DST) and their clinical distinction between endogenous and nonendogenous depression, and one recent study confirmed the validity of DST as a marker for endogenous depression (9). Our study was aimed at determining the incidence of abnormal DST results in PD patients, especially in clinically differentiated subgroups of depressive and nondepressive parkinsonians. ~~

The study comprised 34 patients with PD diagnosed independently by two neurologists. Clinical characteristics of these patients (aged 55.86 t 7.2 years) are given in Table 1. Prior to the initiation of the study, all medical therapy was discontinued for 5-7 days, while the patients were allowed to become familiar with hospital environment. Patients were not included in the study unless they met medical and pharmacological exclusion criteria for DST (10,ll). After 5-7 days in the hospital environment, patients had a baseline 8 a.m. blood cortisol determination. The DST was carried out by administering 1 mg dexamethasone orally at 1 1 p.m. that evening; blood was sampled the next day at 8 a.m. and 4 p.m. A cortisol value of 5 pg/dL or greater after dexamethasone administration identified dexamethasone “nonsuppressors”; this value is accepted for patients with endogenous depression (10,12,13). As Reding et al. (11) proposed, to allow the widest comparison of our results with those in the literature, we also tabulated our results for 8 a.m. and 4 p.m. separately and as a combination of “either or both abnormal” and “both abnormal” (Table 2). A day after DST initiation, the patients were as-

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Address correspondence and reprint requests to Dr. Vladimir S. KostiC, NeuroloSka klinika KCMF, ul. Dr SubotiCa 6, 11000 Belgrade, Yugoslavia.

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sessed clinically. A clinical diagnosis of depression was made independently by two psychiatrists (N.c-s. and D.P.), using the interview schedule that yielded diagnoses according to criteria of the third edition of the Diagnostic and Statistical Manual o f M e n t a l Disorders (DSM-111) (14). To measure the severity of depression, the Hamilton rating scale for depression (15) was completed. This includes 21 two- to four-point scales far rating the severity of depressive symptoms. Total scores range from 0 to 71, with a score of 17 or more indicative of moderate to severe depression (7). Patients with other psychiatric disorders were excluded. The impairment of motor function was estimated according to a previously published scale (16). All the assessments were made “blind” to DST results. According to the listed tests, our PD patients were retrospectively divided in two subgroups: the depressive ones and the nondepressive ones. Clinical features of these subgroups are presented in Table 1. Blood samples were collected and processed according to the previously published procedure ( 1 1). Plasma samples were assayed for cortisol utilizing a commercially available radioimmunoassay kit. Intraassay and interassay coefficients were 3% and 8%, respectively. The control group consisted of 16 healthy volunteers (Table 1). For statistical analysis, Student’s t test, x2 test and linear regression analysis were used. RESULTS The percentages of abnormal DST responses in the control group and the groups of depressed and nondepressed PD patients are shown on Table 2. If

TABLE 1. Profile of patients with Parkinson’s disease (PO)

Controls

Depressed PD patients

Nondepressed PD patients

No of patients 16 16 18 58.3 2 5.9 56.2 ? 7.4 55.7 2 7.1 Age 2 SD (years) 9 9 10 N o of women Duration of disease 4.6 t 2.7 3.93 2 2.43 (years) Hamilton depression score 2 SD 0 26.95 2 4.8 11.46 It 3.15 0 87.3 2 8.5 81.07 2 7.07 PDE“ score -t SD a

PDE, Parkinson’s disease evaluation.

Movement Disorders, Vol. 5 , No. 1, 1990

TABLE 2. Prevalence of an Abnormal Dexamethasone Suppression Test (DST) results in different groups of patients with Parkinson’s disease (PD)”.‘

Controls (n = 16) Depressed PD patients (n = 16) Nondepressed PD patients (n = 18)

Abnormal 8 a.m. cortisol value

Abnormal 4 p.m. cortisol value

Either or both values abnormal

Both values abnormal

6.25 (1)

-

6.25 (1)

-

68.7 (11)

68.7 (11)

75

27.7 (5)

16.6 (3)

27.7 ( 5 )

(12)

62.5 (10) 16.6 (3)

a Abnormal DST is defined as plasma cortisol values greater than 5 &dL at time specified. All values are percentages, with number of patients in parentheses.

either an 8 a.m. or 4 p.m. blood cortisol level greater than 5 kg/dL are accepted as abnormal in cases of endogenous depression, 50% of all the PD patients had abnormal DST results. However, for “either or both values abnormal,” in the group of depressed PD patients 75% were “non-responders”; this value in the group of nondepressed PD patients was significantly lower (27.7%; p < 0.05). Similar differences were recorded at the remaining observed time-points (Table 2). Abnormal DST responses were unrelated to sex, age, and the duration of the disease (Table 1). Although the duration of the disease and PD evaluation (PDE) score (16) were greater in the group of depressed PD patients, that difference did not reach statistical significance. Also, there was no correlation between the values of Hamilton depression score and PDE score (r = 0.357). The only statistically different values are those of Hamilton depression score of the two subgroups (p < 0.05; Table 1). Comparing the results in the groups of depressed and nondepressed PD patients, we determined the specificity of the DST in identifying PD patients with a clinical diagnosis of depression (10,ll). The 8 a.m. and 4 p.m. DST results were found to have the following specificities: 13/18 (72.3%) and 15/18 (83.4%), respectively. For both time points, the sensitivity was the same, 11/16 (68.7%). The baseline 8 a.m. blood cortisol levels before the administration of dexamethasone were not significantly different for “responders” and “nonre1.8 pg/dL, responders” (17.3 ? 2.1 and 17.7 spectively), being in the range of values published for normal subjects (17,18).

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DST IN PARKINSON’S DISEASE COMMENT PD and depression have been frequently associated (1-3), but depression has not been consistently related to any specific aspect of the disease (1). Depression in PD has often been considered as a reaction to the disabling qualities of the illness (2,3), but when compared to the equally disabled patients with other chronic diseases, the prevalence of depression in PD was always significantly higher (5,19,20). Therefore, the possibility of an “organically” based depression intrinsic to the pathobiological substrate(s) of PD has been raised (1). Endogenous depression might also be speculated because, as in our study, there is no relationship between depression and the severity of motor disturbances. Mayeux et al. (1) showed that 43% of their depressed PD patients were depressed before the clinical onset of the disease. Trying to determine more precisely the nature of the depression in our PD patients, the DST was performed as a test supposed to distinguish between two groups of depressed patients whose features are consistent with theoretical predictions inherent in the concepts of endogenous and neuroticlreactive depression (9,12). Interestingly, abnormal DST results were significantly more frequent in our group of depressed parkinsonians compared to the nondepressive PD patients (Table 2), with the values similar to these found in the subjects with endogenous depression (9,12,21). Abnormal DST responses are supposed to be the reflection of disinhibited activity of the hypothalamopituitary-adrenal (HPA) axis, implicated in the pathophysiology of depression (22,23), although the site and precise mechanism of this neuroendocrine dysregulation remain unclear (24). For instance, the disinhibited cortisol secretion in depression is considered to be the result of decreased tonic inhibition due to decreased noradrenergic activity (25), which is also reduced in PD (26). Mayeux et al. (1) proposed an alternative hypothesis that degenerative changes in the brainstem and hypothalamus (part of HPA axis) in the course of PD (27), with the resultant loss of central monoamines, produce or predispose the individual to depression in PD. Our data indicate that the abnormal 8 a.m. and 4 p.m. DST results are reasonably specific (72.3% and 83.4%, respectively) and sensitive (68.7%) indicators of depression in patients with PD. Normal values do not exclude it. However, DST will be

useful clinically only if it has prognostic and therapeutic implications. Different therapeutic procedures are suggested for treatment of depression, depending on the DST results (9), while the possibilities of the test to predict treatment response have been disappointing (21,28). Evaluating the validity of DST in identification of post-stroke depression, Reding et al. (11) suggest that abnormal DST results should be considered a sufficient indicator for initiation of antidepressant therapy. The application of the DST to gain further knowledge on depression and its treatment in PD patients remains the object of additional, further studies.

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Dexamethasone suppression test in patients with Parkinson's disease.

The Dexamethasone Suppression Test (DST), supposed to effectively distinguish between endogenous and nonendogenous depression, was performed in a grou...
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