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The dexamethasone suppression test (DST) and platelet monoamine oxidase (MAO) activity as predictors of psychosis in depression
390
BIOL PSYCHIATRY 1986;21:39&393
CASE REPORT
The Dexamethasone Suppression Test (DST) and Platelet Monoamine Oxidase (MAO) Activity as Predictors of Psychosis in Depression Kerry L. Bloomingdale,
Russell G. Vasile, Jon E. Gudeman.
Benjamin Gerson, and Joseph J. Schildkraut
Introduction The Dexamethasone Suppression Test (DST) has been used extensively to identify patients with endogenous and/or melancholic depressions. Moreover, patients with psychotic forms of endogenous depression have been found to be more likely to have abnormal DSTs than are patients with nonpsychotic forms of these depressions (Carroll et al. 1980; Coryell et al. 1982; Rudorfer et al. 1982; Caroff et al. 1983; Evans et al. 1983; Schatzberg et al. 1983a). Focusing on the specific values of 4:00 PM postdexamethasone serum cortisol levels, rather than simply on the qualitative distinction between suppression and nonsuppression, Schatzberg et al. (1983a) showed that depressed subjects with very high cortisol levels tend to be psychotic. For example, in patients with major depression, they found psychosis in over 70% (7/9) of the patients with postdexamethasone cortisol levels over 15 kg/dl, but in less than 20% (7/36) of the patients with postdexamethasone cortisol levels less than 15 p,g/dl. Platelet monoamine oxidase (MAO) activity has also been widely studied in affective illness. Findings by Meltzer et al. (1980) and by Schildkraut et al. (1977) suggest that high platelet MAO activity might be associated with psychotic depression. particularly in female patients. Furthermore, Schatzberg et al. (1983b) found a significant association between high platelet MAO activity (37.0 nmol tryptamine deaminatedlhrimg protein) and DST nonsuppression in depressed patients. Given the apparent relationship between DST nonsuppression and psychosis in depressed patients. these findings of Schatzberg ct al. would be compatible with an association between high platelet MAO activity and psychotic depression. In the following case report. the authors suggest that the combination ot‘ an extremely
From the Sectwn on Pbychratry, Department of Medicine (K.L.B , R.G V., J.E.G.. J.J S.) and the Psychtatric Chemlatq Laboratory, Department of Pathology (B.C., J.J.S.), New England Deaconess Hospital. Boston, MA; the Neuropsycho pharmacology Laboratory. Massachusetts Mental Health Center (J.E.G.. J.J.S.). Boston MA: and the Department II/ Psychiatry (K.L.B., R.G.V., J.E.G., J.J.S.), Harvard Medical School. Boston. MA Supported m part by NIMH Grants MH 15413 and MH 16259 Address reprint requests tu Dr. Joseph J Schildkraut. Massachusetts Mental Health Center. ?S Penwowi Road. Boston. 22” 02115 Rcce~\cd July 15. IOXS. rw~\ed Octohu i 1985
10 1986 Soclctv of Biolop~cal Paychw\
DST and Platelet MAO in Psychotic Depression
BIOL PSYCHIATRY 1986;21:39&393
391
elevated postdexamethasone cortisol level and very high platelet MAO activity might be a predictor of subsequent psychotic decompensation in depressed patients.
Case Report Ms. A., a 65year-old woman with a diagnosis of major depressive episode, unipolar type, was transferred to the psychiatric service after 6 days on a medical-surgical floor, to which she had been admitted after having taken an overdose of acetaminophen. The patient suffered no systemic damage from the acetaminophen. She had no history of recent weight loss, no significant medical or neurological disease, and, with the exception of the overdose, no history of medication usage during the 2 weeks prior to her admission to our ward. The patient had been treated previously for two depressive episodes, 20 and 8 years ago, respectively. It is unclear whether or not these episodes involved psychotic symptomatology. However, it is known that she had been on no psychoactive medications for over a year prior to admission to our unit. During the patient’s initial week of hospitalization, the absence of psychotic symptoms was specifically noted by four senior psychiatrists, the psychiatric nursing staff, and a psychologist who performed extensive diagnostic testing. The psychological testing, however, did reveal, based on the patient’s Rorschach and TAT responses, a propensity for developing psychosis under stress. Also, during the initial week of hospitalization, while the patient was still drug free, a DST was performed by administering 1 mg dexamethasone po at 11 :OOPM and measuring serum cortisol levels the following day by radioimmunoassay, using a lz51 antibody (Amerlex Cortisol Radioimmunoassay, Amersham Corporation, Arlington Heights, IL). The postdexamethasone cortisol levels were 2.1 p&/d1 at 8:00 AM, 25.2 p,g/dl at 4:OO PM, and 9.6 pg/dl at 11:00 PM. During the same week, her platelet MAO activity, determined as described previously (Schatzberg et al. 1983b), was high, at 11.8 nmol tryptamine deaminated/hr/mg protein. In the middle of the patient’s second week in hospital, while she was still drug free except for lorazepam (1 mg po daily), she suddenly became psychotic. Specifically, she began to insist that the hospital administration had “bugged’ her room with a hidden microphone. She believed herself to be evil and felt that the covert surveillance was, therefore, justifiable. Her depressive symptoms simultaneously worsened. Neither her depressive nor her psychotic symptoms responded to a neuroleptic in combination with a tricyclic antidepressant or to a neuroleptic in combination with lithium carbonate. In fact, she did not improve until she was midway through a course of electroconvulsive therapy (ECT), which began during her eighth week in hospital. As shown in Table 1, the patient’s postdexamethasone cortisol levels remained high, and her platelet MAO activity stayed relatively elevated during the 7 weeks in hospital prior to the initiation of the ECT.
Discussion The relative magnitude of our patient’s elevated initial 4:00 PM postdexamethasone cortisol level of 25.2 kg/d1 can be assessed in the context of unpublished data from a series of 20 depressed patients subsequently hospitalized on our ward. Of these patients, none of whom were taking psychoactive medication other than benzodiazepines, only one had a
392
BIOL PSYCHIATRY 1986;21:390-393
K.L. Bloomingdale
Table 1. Postdexamethasone
Cortisol Level, Platelet MAO Activity, and Clinical State
HospitalizedDepressed Patient
-.~
et al.
in a
-..-- _._.. ..~-.-. __l_-._““---~_-_.
“-
I:00 PM Week in hospital
-___-..
Postde~a~~ethas~~ffc ~wtisol”
Platelet MAO activtty” _.-I-.-____ _~_____
I
2% -. .-7
4
;0
13.5
i
12.0
h
il.
CIinical state
__
Il.8
7
Depressed; nonpsychotic Depressed; psychotic
Depressed; psychotic
9.4 5 ;
Ii
Depressed; psychotic Nondepressed. nonpsychotlc
92
‘The 403 PM postdexamethasone cortisol levels are expressedIII ~tgidl hPlateiet MAO activity is expressed in nmol tryptamitte deaminate&hr/mg
protein
~stdexamethasone cortisol IeveI at either 890 AM, 4:oO PM, or I I:00 PM that was X5.2 IJ.g/dl. The magnitude of the patient’s high initial platelet MAO activity level of 11.8 nmoi tryptamine/hr/mg protein can be illustrated by again examining our unpublished data. The platelet MAO activity levels of 28 depressed patients, ail of whom were free of psychoactive medications other than benzodiazepines, ranged from 4.3 to I 1.7, with a mean of 7.8 nmol t~pt~ine/~/mg protein. In summ~, our case material reveals the coexistence within the same depressed patient of the following four phenomena: (1) a very high pretreatment postdexamethasone cortisol level, (2) a high pretreatment platelet MAO activity, (3) a psychotic decompensation subsequent to the collection of these data, and (4) a positive response to EC?‘. Although this coexistence may have been due to chance alone, as the literature also suggests the possibility of a systematic relationship between these laboratory values and the clinical findings, we wish to alert other investigators to look for similar cases. Thub, in nonpsychotic patients with depression, very high ~stdexamethasone cortisol levels,, particularly in combination with high platelet MAO activity if the patient is female, may suggest the possibility of a subsequent psychotic decompensation and the potential clinical utility of ECT.
References Caroff S. Winok~rA. Ricger M;. Schweizcr E. A~~~terdarn J ( 19831:Kcsponsc to d~~arnethas~)n~ in psychotic depression. ~‘.s~~~~~~~~~ Rc,\ X5944. CUITOII B, Grcden J. Fcinberg M. James N, Hackett K. Steiner M. Tarika J
dysfunction
in genetic subtypes of primary unipolar depression.
(1980): Neuroendocrinr Psychiutry Ra 1:2S I-258.
Coryell W, Gaffney G, Burkhardt P (1982): The dexamethasone suppression test and familial subtypes of depression-A naturalistic replication. Bid Psychiatry 17:?340. Evans D. Bumell G, Nemeroff
Am J P,gdziutt?.
C (1983): Dexamethasone
I 40:586--S8c~
suppression
test in the chnical setting
DST and Platelet MAO in Psychotic
Depression
BIOL PSYCHIATRY 1986;21:390-393
393
Meltzer H, Arora R, Jackman H, Pscheid TG, Smith M (1980): Platelet MAO and plasma MAO in psychiatric patients. Schizophren Bull 6:213-219. Rudorfer M, Hwu H-G, Clayton PJ (1982): Dexamethasone suppression test in primary depression: Significance of family history and psychosis. Biol Psychiatry 17:41-48. Schatzberg A, Rothschild A, Stahl J, Bond T, Rosenbaum A, Lofgren S, MacLaughlin R, Sullivan M, Cole J (1983a): The dexamethasone suppression test: Identification of subtypes of depression. Am J Psych&y 140:88-91. Schatzberg A, Orsulak P, Rothschild A, Solomon M, Lerbinger J, Kizuka P, Cole J, Schildkraut J (1983b): Platelet MAO activity and the dexamethasone suppression test in depressed patients. Am J Psychiatry 140:1231-1233. Schildkraut J, Orsulak P, Gudeman J, Schatzberg A, Rohde W, LaBrie L, Cahill J, Cole J, Frazier S (1977): Norepinephrine metabolism in subtypes of depressive disorders. In Shagass C, Gershon S, Friedhoff A (eds), Psychopathology and Bruin Dysfunction. New York: Raven Press, pp 125-138.
BIOL PSYCHIATRY 1986;21:39&393
CASE REPORT
The Dexamethasone Suppression Test (DST) and Platelet Monoamine Oxidase (MAO) Activity as Predictors of Psychosis in Depression Kerry L. Bloomingdale,
Russell G. Vasile, Jon E. Gudeman.
Benjamin Gerson, and Joseph J. Schildkraut
Introduction The Dexamethasone Suppression Test (DST) has been used extensively to identify patients with endogenous and/or melancholic depressions. Moreover, patients with psychotic forms of endogenous depression have been found to be more likely to have abnormal DSTs than are patients with nonpsychotic forms of these depressions (Carroll et al. 1980; Coryell et al. 1982; Rudorfer et al. 1982; Caroff et al. 1983; Evans et al. 1983; Schatzberg et al. 1983a). Focusing on the specific values of 4:00 PM postdexamethasone serum cortisol levels, rather than simply on the qualitative distinction between suppression and nonsuppression, Schatzberg et al. (1983a) showed that depressed subjects with very high cortisol levels tend to be psychotic. For example, in patients with major depression, they found psychosis in over 70% (7/9) of the patients with postdexamethasone cortisol levels over 15 kg/dl, but in less than 20% (7/36) of the patients with postdexamethasone cortisol levels less than 15 p,g/dl. Platelet monoamine oxidase (MAO) activity has also been widely studied in affective illness. Findings by Meltzer et al. (1980) and by Schildkraut et al. (1977) suggest that high platelet MAO activity might be associated with psychotic depression. particularly in female patients. Furthermore, Schatzberg et al. (1983b) found a significant association between high platelet MAO activity (37.0 nmol tryptamine deaminatedlhrimg protein) and DST nonsuppression in depressed patients. Given the apparent relationship between DST nonsuppression and psychosis in depressed patients. these findings of Schatzberg ct al. would be compatible with an association between high platelet MAO activity and psychotic depression. In the following case report. the authors suggest that the combination ot‘ an extremely
From the Sectwn on Pbychratry, Department of Medicine (K.L.B , R.G V., J.E.G.. J.J S.) and the Psychtatric Chemlatq Laboratory, Department of Pathology (B.C., J.J.S.), New England Deaconess Hospital. Boston, MA; the Neuropsycho pharmacology Laboratory. Massachusetts Mental Health Center (J.E.G.. J.J.S.). Boston MA: and the Department II/ Psychiatry (K.L.B., R.G.V., J.E.G., J.J.S.), Harvard Medical School. Boston. MA Supported m part by NIMH Grants MH 15413 and MH 16259 Address reprint requests tu Dr. Joseph J Schildkraut. Massachusetts Mental Health Center. ?S Penwowi Road. Boston. 22” 02115 Rcce~\cd July 15. IOXS. rw~\ed Octohu i 1985
10 1986 Soclctv of Biolop~cal Paychw\
DST and Platelet MAO in Psychotic Depression
BIOL PSYCHIATRY 1986;21:39&393
391
elevated postdexamethasone cortisol level and very high platelet MAO activity might be a predictor of subsequent psychotic decompensation in depressed patients.
Case Report Ms. A., a 65year-old woman with a diagnosis of major depressive episode, unipolar type, was transferred to the psychiatric service after 6 days on a medical-surgical floor, to which she had been admitted after having taken an overdose of acetaminophen. The patient suffered no systemic damage from the acetaminophen. She had no history of recent weight loss, no significant medical or neurological disease, and, with the exception of the overdose, no history of medication usage during the 2 weeks prior to her admission to our ward. The patient had been treated previously for two depressive episodes, 20 and 8 years ago, respectively. It is unclear whether or not these episodes involved psychotic symptomatology. However, it is known that she had been on no psychoactive medications for over a year prior to admission to our unit. During the patient’s initial week of hospitalization, the absence of psychotic symptoms was specifically noted by four senior psychiatrists, the psychiatric nursing staff, and a psychologist who performed extensive diagnostic testing. The psychological testing, however, did reveal, based on the patient’s Rorschach and TAT responses, a propensity for developing psychosis under stress. Also, during the initial week of hospitalization, while the patient was still drug free, a DST was performed by administering 1 mg dexamethasone po at 11 :OOPM and measuring serum cortisol levels the following day by radioimmunoassay, using a lz51 antibody (Amerlex Cortisol Radioimmunoassay, Amersham Corporation, Arlington Heights, IL). The postdexamethasone cortisol levels were 2.1 p&/d1 at 8:00 AM, 25.2 p,g/dl at 4:OO PM, and 9.6 pg/dl at 11:00 PM. During the same week, her platelet MAO activity, determined as described previously (Schatzberg et al. 1983b), was high, at 11.8 nmol tryptamine deaminated/hr/mg protein. In the middle of the patient’s second week in hospital, while she was still drug free except for lorazepam (1 mg po daily), she suddenly became psychotic. Specifically, she began to insist that the hospital administration had “bugged’ her room with a hidden microphone. She believed herself to be evil and felt that the covert surveillance was, therefore, justifiable. Her depressive symptoms simultaneously worsened. Neither her depressive nor her psychotic symptoms responded to a neuroleptic in combination with a tricyclic antidepressant or to a neuroleptic in combination with lithium carbonate. In fact, she did not improve until she was midway through a course of electroconvulsive therapy (ECT), which began during her eighth week in hospital. As shown in Table 1, the patient’s postdexamethasone cortisol levels remained high, and her platelet MAO activity stayed relatively elevated during the 7 weeks in hospital prior to the initiation of the ECT.
Discussion The relative magnitude of our patient’s elevated initial 4:00 PM postdexamethasone cortisol level of 25.2 kg/d1 can be assessed in the context of unpublished data from a series of 20 depressed patients subsequently hospitalized on our ward. Of these patients, none of whom were taking psychoactive medication other than benzodiazepines, only one had a
392
BIOL PSYCHIATRY 1986;21:390-393
K.L. Bloomingdale
Table 1. Postdexamethasone
Cortisol Level, Platelet MAO Activity, and Clinical State
HospitalizedDepressed Patient
-.~
et al.
in a
-..-- _._.. ..~-.-. __l_-._““---~_-_.
“-
I:00 PM Week in hospital
-___-..
Postde~a~~ethas~~ffc ~wtisol”
Platelet MAO activtty” _.-I-.-____ _~_____
I
2% -. .-7
4
;0
13.5
i
12.0
h
il.
CIinical state
__
Il.8
7
Depressed; nonpsychotic Depressed; psychotic
Depressed; psychotic
9.4 5 ;
Ii
Depressed; psychotic Nondepressed. nonpsychotlc
92
‘The 403 PM postdexamethasone cortisol levels are expressedIII ~tgidl hPlateiet MAO activity is expressed in nmol tryptamitte deaminate&hr/mg
protein
~stdexamethasone cortisol IeveI at either 890 AM, 4:oO PM, or I I:00 PM that was X5.2 IJ.g/dl. The magnitude of the patient’s high initial platelet MAO activity level of 11.8 nmoi tryptamine/hr/mg protein can be illustrated by again examining our unpublished data. The platelet MAO activity levels of 28 depressed patients, ail of whom were free of psychoactive medications other than benzodiazepines, ranged from 4.3 to I 1.7, with a mean of 7.8 nmol t~pt~ine/~/mg protein. In summ~, our case material reveals the coexistence within the same depressed patient of the following four phenomena: (1) a very high pretreatment postdexamethasone cortisol level, (2) a high pretreatment platelet MAO activity, (3) a psychotic decompensation subsequent to the collection of these data, and (4) a positive response to EC?‘. Although this coexistence may have been due to chance alone, as the literature also suggests the possibility of a systematic relationship between these laboratory values and the clinical findings, we wish to alert other investigators to look for similar cases. Thub, in nonpsychotic patients with depression, very high ~stdexamethasone cortisol levels,, particularly in combination with high platelet MAO activity if the patient is female, may suggest the possibility of a subsequent psychotic decompensation and the potential clinical utility of ECT.
References Caroff S. Winok~rA. Ricger M;. Schweizcr E. A~~~terdarn J ( 19831:Kcsponsc to d~~arnethas~)n~ in psychotic depression. ~‘.s~~~~~~~~~ Rc,\ X5944. CUITOII B, Grcden J. Fcinberg M. James N, Hackett K. Steiner M. Tarika J
dysfunction
in genetic subtypes of primary unipolar depression.
(1980): Neuroendocrinr Psychiutry Ra 1:2S I-258.
Coryell W, Gaffney G, Burkhardt P (1982): The dexamethasone suppression test and familial subtypes of depression-A naturalistic replication. Bid Psychiatry 17:?340. Evans D. Bumell G, Nemeroff
Am J P,gdziutt?.
C (1983): Dexamethasone
I 40:586--S8c~
suppression
test in the chnical setting
DST and Platelet MAO in Psychotic
Depression
BIOL PSYCHIATRY 1986;21:390-393
393
Meltzer H, Arora R, Jackman H, Pscheid TG, Smith M (1980): Platelet MAO and plasma MAO in psychiatric patients. Schizophren Bull 6:213-219. Rudorfer M, Hwu H-G, Clayton PJ (1982): Dexamethasone suppression test in primary depression: Significance of family history and psychosis. Biol Psychiatry 17:41-48. Schatzberg A, Rothschild A, Stahl J, Bond T, Rosenbaum A, Lofgren S, MacLaughlin R, Sullivan M, Cole J (1983a): The dexamethasone suppression test: Identification of subtypes of depression. Am J Psych&y 140:88-91. Schatzberg A, Orsulak P, Rothschild A, Solomon M, Lerbinger J, Kizuka P, Cole J, Schildkraut J (1983b): Platelet MAO activity and the dexamethasone suppression test in depressed patients. Am J Psychiatry 140:1231-1233. Schildkraut J, Orsulak P, Gudeman J, Schatzberg A, Rohde W, LaBrie L, Cahill J, Cole J, Frazier S (1977): Norepinephrine metabolism in subtypes of depressive disorders. In Shagass C, Gershon S, Friedhoff A (eds), Psychopathology and Bruin Dysfunction. New York: Raven Press, pp 125-138.