Journal of Affectire Disorders, 24 ( 1992) 87-9 1

87

0 1992 Elsevier Science Publishers B.V. Ali rights reserved 01650327/92/$05.00

JAD 00866

i

Janusz Rybakowski and Malgorzata Plocka Department

of

Psychiatry, Medical Academy, Bydgoszcz, Poland

(Received 30 August 199 1) (Revision received 14 October 1991) (Accepted 30 October 1991)

Summary

The circannual results of the dexamethasone suppression test (DST) were compared in depressed and schizophrenic patients for the periods November-February and March-October. During the winter months, female depressive and schizophrenic patients had lower rates of DST nonsuppression as well as lower concentrations of post-dexamethasone plasma cortisol, compared to the March-October period, despite similar pre-dexamethasone cortisol levels. Male depressed patients had lower pre-dexamethasone cortisol levels during the winter months while male schizophrenics had higher pre- and post-dexamethasone cortisol levels and higher rates of DST nonsuppression. This may suggest less disturbance of HPA axis function in winter months in depressed patients, mostly females, and confirms findings from some previous studies. A gender effect of DST seasonality was also demonstrated, with male schizophrenic patients presenting a reverse DST nonsuppression pattern compared with female depressive and female schizophrenic patients.

Key words: Seasonal variation; Depression; Schizophrenia; suppression test

Gender difference; Cortisol; Dexamethasone

Introduction Address for correspondence: Janusz Rybakowski, MD, PhD, Department of Psychiatry, Medical Academy, ul.Lomzynska 54, 85-863 Bydgoszcz, Poland. * This paper was submitted when the main author was Visiting Scientist at Depression Research Unit, Department of Psychiatry, University of Pennsylvania, Philadelphia.

Evidence for a seasonal variation in results of the dexamethasone suppression test (DST) in depression has been observed in several studies. Arato et al. (1986) showed lower rates of cortisol

nonsuppression in unipolar depressed patients during winter compared to summer months. Similarly, Swade et al. (1987) reported significantly lower post-dexamethasone plasma cortisol levels in depressed patients during the period from November to February compared to the rest of the year. In both these studies, the tendency toward lower cortisol nonsuppression rates observed in winter months was somewhat difficult to explain, in view of increased rates of depressive illness during this season. Moreover. two subsequent studies were not able to replicate these initial results (Van Bemmel et al., 1988; Harris et al., 1990). While the DST has most often been utilized as a diagnostic aid for depression, the pathophysiological significance of the DST remains enigmatic with positive results found in a substantial proportion of patients with schizophrenia (Yeragani, 1990) and other illnesses (Cameron et al., 19136; Lindy et al., 1985). Furthermore, the factors associated with cortisol nonsuppression in s’ hizophrenia may be different from those in depression. For example, neuroleptic-free status has been shown to be one important influence on DST nonsuppression in schizophrenia (Tandon et al., 1991). A possible seasonal variation in DST results has been found in depression but its relationship to schizophrenia has so far not been considered. In this study, we addressed the issue of seasonal variation of the DST in depressive patients compared to those with schizophrenia.

moderate intensity of symptoms as assessed on the day of study by means of the 17-item Hamilton Depression Scale (HDS) (Hami!:on, 1960) and the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham, 1962), with the modification of Beth et al. (1986). The intensity of symptoms in any depressed patient was not less than 15 poims on HDS and in any schizophrenic patient not less than 15 points on BPRS. Dexamethasone, 1.0 mg, was administered orally at 11:OOp.m. Blood samples were collected at 4:OOp.m. on the day before the DST and at 4:00 p.m. and 11:OOp.m. after dexamethasone. Plasma cortisol concentrations were determined by means of a polarized immunofluorescence assay technique (Abbott TDX system). A postdexamethasone cortisol concentration > 5 pg,/dl at 4:00 p.m. and/or 11:OOp.m. was defined as nonsuppression. Non-parametric chi-square and Mann-Whitney tests were used in statistical calculations. In view of the original results of Arato et al. (19863 and Swade et al. (19871, the period NovemberFebruary was compared with the rest of the year. The data were analyzed separately according to diagnosis and gender. Results

Table 1 summarizes the number and percentage of DST nonsuppressors in male and female

TABLE

Patients and methods

The study was performed on 186 inpatients of the Department of Psychiatry, Medical Academy, Bydgoszcz, hospitalized over the period 19861990. There were 81 patients with depression (22 male, 59 female) aged 22-70 years (mean 41 ) 12 years) and 105 patients with schizophrenia (70 male, 35 female) aged 18-54 years (mean 28 + 8 years). Among patients with depression, 17 were diagnosed as having bipolar and 64 unipolar affective illness. All diagnoses were confirmed using DSM-III R criteria. The DST was i)erformed when patients had been drug-free for at least 7-10 days and showed

I

DST RESULTS IN MALE AND FEMALE PATIENTS WITH DEPRESSION AND SCHIZOPHRENIA IN THE PERIODS NOVEMBER-FEBRUARY AND MARCHOCTOBER Diagnosis

November-February I1 nonsuppressors n

Depression Male Female Schizophrenia Male Female

March-October

t1

r/r

nonsuppressor! n

%

7 14

3 3

43 21

15 4s

6 18

40 40

26

12

46

44

12

I6

4

2s

19

8

27 42

89

patients with depression and schizophrenia in the two analyzed periods. The percentage of female patients with depression and female patients with schizophrenia showing cortisol nonsuppression was lower during winter (21% and 25%, respectively) compared with the rest of the year (40% and 42%). This, however, did not reach statistical significance by means of the chi-square test. No such difference between analyzed periods was observed in male depressed patients (43% vs. 40%). On the other hand, the cortisol nonsuppression rate in schizophrenic male patients was higher ir, the November-February period (46%) compared with March-October (27%) although again not statistically significant on the chi-square test. In Table 2, the mean values of plasma cortisol levels measured at 4:00 p.m. on the pre-dexamethasone day, and 17 and 24 h folluwing dexamethasone administration, in male and female patients with depression and schizophrenia are compared for the periods November-February and March-October. The differences obtained between these two periods can be summarized as follows: (1) predexamethasone cortisol levels at 4:00 p.m. in the winter months compared with the rest of the year were lower in male depressives and higher in male schizophrenics; (2) 17-h post-dexamethasone cortisol levels in the winter months compared with the rest of the years were significantly lower in female depressives and female schizophrenics but significantly higher in male

TABLE

schizophrenics; (3) 24-h post-dexamethasone cot-tisol levels in the winter months compared with the rest of the year were significantly lower in female depressives but higher in male schizophrenics. iscussion In this study, we demonstrated a lower rate of cortisol nonsuppression to DST and lower postdexamethasone plasma cortisol concentration during the winter months (November-February) in female depressed and schizophrenic patients. This observation was not due to seasonal differences in pre-dexamethasone basal cortisol levels in these groups of patients. These data may confirm the observations reported by Arato et al. (1986) and Swade et al. (1987). In male depressed patients, we found lower pre-dexamethasone cortisol levels in the winter months but no difference between the two analyzed periods regarding post-dexamethasone cortisol concentrations. Because the number of depressed male patients in our study was relatively small, it is possible that a lower proportion of male patients might have influenced the results for the total sample of depressive subjects, both in ours and in previous studies. On the other hand, our data fit the recent ieyort on the seasonal variation of parasuicides where a significant fall in the number of parasuicides was shown in winter for female subjects with no difference in seasonal variation among men (Masterton, 1991).

2

PLASMA CORTISOL LEVELS (pg/dl; DEPRESSION AND SCHIZOPHRENIA Diagnosis

pre

FEMALE PATIENTS WITH AND MARCH-OCTOBER

March-October

November-February n

Depression Male

MEANS+SEM) DURING DST IN MALE AND DURING THE PERIODS NOVEMBER-FEBRUARY

17-h

24-h

n

pre

17-h

24-h

7

8.9+ 1.9

Female

14

O.O+T _ -.-c

4.3 + 2.3 3.1 * 1.4

2.7-k 1.2 2.4 + 0.8

15 45

12.3+ 1.4 # 9.5 J_ 1.0

4.9-k 1.3 4.lkO.8 ‘>

3.8+0.9 3.6kO.6 #

Schizophrenia Male Female

26 16

13.8+ 1.2 10.6 f 1.5

5.6k 1.0 3.8 + 2.1

4.6kl.l 3.7+ 1.1

44 19

10.7+0.8 11.3k1.3

3.7kO.6 * 5.6+ 1.4 *

3.5 + 0.6 # 4.4 f 0.9

* Difference # Difference

VP. November-February vs. November-February

P < 0.05 (Mann-Whitney P = 0.05 (Mann-Whitney

test). test).

*

Our results may suggest the possibility of a seasonal variation of HP.4 axis functional activity and its response to dexamethasone in psychiatric patients. This may be due to aherations of corfisol and/or dexamethasone metabolism during winter months leading to less disturbance of the HPA axis in depressed patients. The directions of these changes appear opposite to the clinical observations of increased depressive morbidity during the winter (Rosenthal and Wehr, 1987). Furthermore, several investigators have reported a seasonal difference in serotonin metabolism with an increasing activity during winter months (Arora et al., 1984, Brewerton, 1989). Thus, an adaptational role of lower cortisol and higher serotonin status during winter months in depressed patients may be G: 1 possible mechanism to account for the seasonal dliference in DST results. Another finding of our study is i\ gender difference in the seasonal variation of DST in bo,th depressive and schizophrenic pcltients. Male schizophrenic patients showed a reverse pattern of this seasonality when compared with depressed and schizophrenic females. During the winter months, schizophrenic males had higher predexamethasone cortisol levels and 17- and 24-h post-dexamethasone cortisol concentrations. Our data on DST seasonality may contribute to other clinical and biochemical observations highlighting gender differences in schizophrenia and a possibBe relation of female schizophrenia to affective illness (Flor-Henry, 1990). Several issues arising from the study design warrant further comment. Healthy subjects were not studied as a comparison group and it is possible that they might also show a seasonal variation in cortisol response to dexarnethasone. To our knowledge, there has been no systematic study in either the psychiatric or the endocrinological 1::erature addressing this issue. The reference group for our depressed patients was drugfree schizophrenic subjects who showed substantial HPA axis disttlrbances. It is not known whether depressed parlents parallel the seasonality of healthy controls with DST as is the case with serotonin reuptake (Arora et al., 1984). Furthermore, most of our female patients were premenopausal, and the study did not consider the

phase of their menstrual cycle. Post-dexamethasone cortisol levels in depressed patients have been shown to be dependent on the menstrual cycle, with the highest concentration in the ovulatory period and the lowest during menses (Tandon et al., 1990). However, the preponderance of females makes it possible that this bias was insignificant. Finally, this study was performed in the northern hemisphere, in a moderate climate, and the present observation may be limited to this latitude. It would be interesting to know the results of similar studies performed in the southern hemisphere. In conclusion, observations from the present study indicate less disturbance of HPA axis function in winter months in depressed female patients. A gender effect on the seasonality of the tort isol response to dexame t hasone suppression is evident in both depressed and schizophrenic patients. eferences Arato, M., R:hmer, Z. and Szadoczky, E. (1986) Seasonal influence on the dexamethasone test results in unipolar depression. Arch. Gen. Psychiatry 43, 813. Arora, R.C., Kregel, L. and Meltzer, H.Y. (1984) Seasonal variation of serotonin uptake in normal controls and depressed patients. Biol. Psychiatry 19, 795-804. Beth, P.. Katrup. N. and Rafaelsen, O.J. (1986) Mini-compendium of rating scales for states of anxiety, depression, mania, schizophrenia with corresponding DSM-III syndromes. Acta Psychiatr. Stand. 73, Suppl. 326. Brewerton, T.D. (1989) Seasonal variation of serotonin fdnction in humans: research and clinical implications. Ann. Clin. Psychiatry 1, 153-164. Cameron, O.G., Kerber, K. and Curtis, G.C. (1986) Obsessive-compulsive disorder and the DST. Psychiatry Res. 19,329-330. Flor-Henry, P. (1990) Influence of gender in schizophrenia as reIdted to other psychopathological syndromes. Schizophren. Bull. 16, 21 l-227. Hamilton, M. (1960) A rating scale for depression. J. Neurol.

Neurosurg. Psychiatry 23, 56-62. Lindy, D.C.. Walsh, B.T., Roose, S.P., Gladia, M. and Glassman, A.H. (1985) The dexamethasone suppression test in bulimia. Am. J. Psychiatry 142, 1375-1376. Masterton, G. (1991) Monthly and seasonal variation in parasuicide. A sex difference. Br. J. Psychiatry 158, 155-157. Overall, J.E. and Gorham, D.R. (1962) The Brief Psychiatric Rating Scale. Psychol. Rep. 10, 799-812. Rosenthal, N.E. and Wehr, T.A. (1987) Seasonal affective disorders. Psychiatr. Ann. 17, 670-674.

91 Fwade, C., Metcalfe, M., Coppen, A., Mendlewicz, J. and Linkowski, P. (1987) Seasonal variations in the dexamethasane suppression test. J. Affect. Disord. 13, 9-l 1. Tandon, R., Hasketi. R.F., Cardona, D., Alcser, K. and Greden, J.F. (1990) Menstrual cyc!e effects on the dexamethasone suppression test in major depression. Biol. Psychiatry 28,485488. Tandon, R., Mazzara, C., DeQuardo, J., Craig, K.A., Meador-Woodruff, J.H., Goldman, R. and Greden, J.F. (1991) Dexamethasone suppression test in schizophrenia:

relationship to symptomatology, ventricular enlargement, and outcome. E~ol. Psychiatry 29, 953-964. Van Bemmel, A.L., Van Diest, R., Smeets, E.H.J., Van Dongen, P.H.M. and Hilgersom, A.J.C. (1988) Seasonal variation of cortisol plasma levels in depressives. J. Affect. Disord. 15, 191-193. Yeragani, V.K. (1990) The incidence of abnormal dexamethasone suppression in schizophrenia: a review and a metaanalytic comparison with the incidence in normal controIs. Can. J. Psychiatry 35, 128-132.

Seasonal variations of the dexamethasone suppression test in depression compared with schizophrenia: a gender effect.

The circannual results of the dexamethasone suppression test (DST) were compared in depressed and schizophrenic patients for the periods November-Febr...
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