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The dexamethasone suppression and thyrotropin-releasing hormone tests in depressed borderline patients
P~v('honeuroendot'rinoh~r, Vol. 8. No. 4, p p . 459
462, 1983.
0306 - 4 5 3 0 / 8 3 $ 3 . 0 0 + 0 . 0 0 ~ 1983 P e r g a m o n Press Ltd.
P r i n l e d in (,ireat B r i t a i n .
SHORT COMMUNICATION THE D E X A M E T H A S O N E S U P P R E S S I O N A N D T H Y R O T R O P I N - R E L E A S I N G H O R M O N E TESTS IN DEPRESSED BORDERLINE PATIENTS HARVEY A. STERNBACH,*:~ JAN FLEMING, II IRL EXTEIN,* A. L. C. POTTASH*~ and MARK S. GOLD*'t *Fair Oaks Hospital and the ~Psychiatric Diagnostic Laboratories of America Summit, NJ; :l:Department of Psychiatry, West Los Angeles VA Medical Center, Brentwood Division. and UCLA-Neuropsychiatric Institute, Los Angeles; §Falkirk Hospital, Central Valley, NY; and the IIUniversity of Toronto, Faculty of Medicine, Toronto, Canada
(Received 15 October 1982; in final form 15 I"ebruao' 1983) SUMMARY Borderline patients can be both a diagnostic and a therapeutic enigma. We investigated a group of 24 depressed women with borderline personality disorder or strong borderline features by DSM 111 criteria for the presence of either an abnormal dexamethasone suppression test (DST) or a blunted TSH response to TRH, abnormalities which have been reported in major depression. Thirteen of the 24 borderlines failed to suppress on the DST, compared with one of 14 normal women (p < 0.01). Nine of the 24 borderlines had a blunted TSH response to TRH, compared with one of 11 normal women. Neuroendocrine abnormalities were found in a total of 75°/0 of the borderline women, independent of whether or not they met DSM 111 criteria for major depressive disorder. The results of this study support the notion that many borderline patients with depression have a genuine affective component to their illness, perhaps biologically similar to major depression in non-borderlines. INTRODUCTION THE DIAGNOSIS and t r e a t m e n t o f the " b o r d e r l i n e " patient is o n e o f the most difficult and c o n t r o v e r s i a l areas o f psychiatry. B o r d e r l i n e disorders are generally expressed in c h a r a c t e r o l o g i c a l terms and d e f i n e d by various traits such as a f f e c t i v e instability, impulsivity, identity disturbance, intense interpersonal relationships (American Psychiatric A s s o c i a t i o n , 1980), and even b r ie f psychotic episodes ( G u n d e r s o n & Singer, 1975). W h e n such patients c o m p l a i n o f feeling depressed, their d y sp h o r i c m o o d state is usually c o n s i d e r e d to be " n e u r o t i c " in n a t u r e and o f t en i n t er p r et ed in p s y c h o a n a l y t i c terms. C a r r o l l et al. (1981a) recently have reviewed s o m e o f the diagnostic difficulties in assessing patients with b o r d e r l i n e disorders, and A ki sk al (1981) has reviewed the rationale b e h i n d c o n s i d e r i n g b o r d e r l i n e disorders in the realm o f a " s u b a f f e c t i v e " rather than a " s u b s c h i z o p h r e n i c " illness. T h e cortisol response to d e x a m e t h a s o n e and the t h y r o t r o p i n ( T S H ) response to t h y r o t r o p i n - r e l e a s i n g h o r m o n e ( T R H ) have been s h o w n to be useful diagnostic aids in the e v a l u a t i o n o f e n d o g e n o m o r p h i c depression (Carroll et al., 1981b; G o l d et al., 1981; K i r k e g a a r d , 1981; L o o s e n & P r a n g e , 1982; S t e r n b a c h et al., 1982). Decisions regarding the t r e a t m e n t o f b o r d e r l i n e patients with either a n t i d ep r essan t s or lithium could be aided by the presence o f a biological m a r k e r such as an a b n o r m a l d e x a m e t h a s o n e suppression Address correspondence to: Dr. Harvey Sternbach, Brentwood V. A. Medical Center, 11301 Wilshire Blvd., Los P.ngeles, CA 90073, U.S.A. 459
460 test ( D S T ) o r T R H D S T s in 13 o f endogenomorphic We report here
HARVEY A. STERNBACHet al. test. C a r r o l l e t a l . ( 1 9 8 1 a ) h a v e r e p o r t e d o n t h e p r e s e n c e o f a b n o r m a l 21 b o r d e r l i n e patients, consistent with such patients having depression. t h e r e s u l t s o f a n i n v e s t i g a t i o n o f n e u r o e n d o c r i n e a b n o r m a l i t i e s in 24
w o m e n w i t h f e a t u r e s o f b o r d e r l i n e p e r s o n a l i t y d i s o r d e r b y D S M 111 c r i t e r i a . T h e r e s u l t s o f this study indicate that such women are clinically and neuroendocrinologically similar to p a t i e n t s w i t h m a j o r d e p r e s s i v e d i s o r d e r b y D S M II1 c r i t e r i a . PATIENTS AND METHODS Subjects for this study consisted of 24 women, age range 14-54 yrs, mean age _+ S.D. ~ 27.7 + 10.1, consecutively admitted to Fair Oaks Hospital's Neuropsychiatric Evaluation Unit ~ith a diagnosis of borderline personality disorder or borderline personality features. Thirteen of these women fulfilled strict DSM-III criteria for borderline personality disorder (five or more of the eight criteria), while the remaining I 1 patients met four of eight criteria and were categorized by the authors as having "mixed" personality disorders with strong borderline features. None of the 24 patients had abused drugs or alcohol for at least one month prior to admission. All patients had normal physical examinations and routine laboratory testing, and none had taken within the previous week medications that would interfere with the DST or TRH tests (e.g. barbiturates, aspirin, thyroid hormone, etc.L All 24 patients underwent systematic neuroendocrine evaluation with the 1 mg dexamethasone suppression test (Carroll el al., 1981b) and the 500 ~.g TRH test (Extein et al., 1981). In all cases, patients first had the TRH test, followed at least one, but no more than three days later by the DST. None of the 24 patients had abnormal basal thyroid function tests (TSH, T3 uptake, T3 RIA, T4). For the TRH test, serum TSH was measured by radioimmunoassay (Hall et al., 1971) at 0, 15, 30, 60 and 90 rain after TRH injection at 0900 hr. The Lx max TSH (peak TSH minus baseline) was calculated for each patient. Any patient with a A max TSH < 7 talU ml was considered to have a blunted TSH response to TRH (Extein et al., 1981). For comparison, we used an agedmatched control group of 11 normal volunteer women ~ho, on inter~ie~, had no personal or family history of psychiatric illness and who consented to TRH testing (mean age 31.9 _+9.0 yrs). For the DST, patients were given dexamethasone (1 mg p.o.) at 2300 hr with serum collected at 0800, 120(I. 160(I and 2355 hr the next day, serum cortisol was measured in duplicate by radioimmunoassay (Donahue & Sgontas, 1975). Any cortisol concentration >~ 5 ~tg/dl was considered to be non-suppression (Carroll el al., 198l b). For comparison ~e used an age-matched control group of 14 normal vohmteer ~omen ~ho, by intervie~, had no personal or famib history of psychiatric illness and who consented to have the DST (mean age 28.6 + 5.6 yrs). Statistical analysis was performed with the Fisher exact test, Student's t-test and chi-square test, as appropriate. RESULTS T a b l e I i n d i c a t e s t h a t , o f t h e 24 b o r d e r l i n e p a t i e n t s s t u d i e d , 17 ( 7 1 % ) m e t D S M i l l c r i t e r i a f o r m a j o r d e p r e s s i v e d i s o r d e r , a n d t h e r e m a i n i n g s e v e n p a t i e n t s all h a d d e p r e s s i v e f e a t u r e s . T h e r e w a s n o s i g n i f i c a n t d i f f e r e n c e in a g e b e t w e e n t h o s e p a t i e n t s w i t h ( 2 9 . 0 _+ 10 yrs), a n d w i t h o u t ( 2 4 . 4 _+ 7.8 yrs), m a j o r d e p r e s s i v e d i s o r d e r (I = 1.11, p = ns). E l e v e n o f t h e 17 p a t i e n t s ( 6 5 % ) m e e t i n g c r i t e r i a f o r m a j o r d e p r e s s i v e d i s o r d e r h a d a n a b n o r m a l DST, while 2 of 7 patients (29%) without major depression also had an abnormal DST. O n t h e T R H test, 7 o f 17 p a t i e n t s ( 4 1 % } w i t h m a j o r d e p r e s s i o n h a d a b l u n t e d T S H response to TRH, while 2 of 7 patients (29%) without major depression had such a r e s p o n s e . A l t h o u g h t h e r e w a s a t r e n d f o r a h i g h e r p r o p o r t i o n o f n o n - s u p p r e s s o r s in borderlines with major depression, there was no significant difference between those patients with and without major depression with regard to the presence of an abnormal D S T o r T R H test ( F i s h e r e x a c t test, p = 0 . 1 0 a n d p = 0 . 3 1 , r e s p e c t i v e l y ) . F u r t h e r , t h e r e w a s n o s i g n i f i c a n t d i f f e r e n c e in D S T o r T R H test a b n o r m a l i t i e s b e t w e e n t h e 13 p a t i e n t s w h o m e t five o f e i g h t D S M 111 c r i t e r i a f o r b o r d e r l i n e p e r s o n a l i t y d i s o r d e r (10 h a v i n g major depression) and the I 1 patients meeting four of eight DSM-III criteria for the same d i s o r d e r ( s e v e n w i t h m a j o r d e p r e s s i o n ) F i s h e r e x a c t test, p = 0 . 1 4 . T h e r e w a s n o
D S T AND T R H
IN BORDERLINE PERSONAtITY
461
TABLE [. DEXAMETHASONE SUPPRESSION TEST ( D S T ) AND T S H RESPONSES TO T R H
Patient
Age
I 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
19 36 22 39 54 33 33
36 24 14 24 27 37 16 40 20 19 26 15 19 31 37 25 18
IN BORDERLINE PATIENTS
DSM-III borderline criteria m e t
Depression: major vs non-major
Abnormal DST
Blunted ix m a x T S H
5 5 5 4 4 4 5 6 5 5 4 5 4 5 4 4 5 5 5 4 4 5 4 4
M M M M M M M M M M M M M M M M M NM NM NM NM NM NM NM
+ + + + + + + + + + + + + -
+ + + + + + + + + -
significant difference in age between DST suppressors and non-suppressors (26.0 _+ 12.0 vs 29.1 _+ 8.6 yrs, respectively) or the blunted vs normal TSH responders (30.3 _+ 10.9 vs 26. l _ 9.4 yrs, respectively). Of further note is the finding that, of the 13 patients with an abnormal DST, an elevated cortisol was found at 20 of a possible 52 time points: there were no abnormal cortisol values at 0800 hr, three abnormal values at 1200 hr, eight elevated cortisol levels at 1600 hr, and nine such elevated levels at 2355 hr. When we compared these borderline patients as a group with the normal female volunteers, there was a statistically significantly higher prevalence of DST nonsuppressors in the borderlines (17 of 24) compared with the normals (1 of 14) (X 2 = 9.91, df = l, p < 0.01). There was a non-significant trend for the borderline group to have more blunted TSH responses (9 of 24) compared with the normals (1 of I l) (X 2 = 2.95, df = I, p < 0.10). As a group, 18 of the 24 borderline patients (75070) had at least one neuroendocrine abnormality. DISCUSSION
The results of this preliminary investigation indicate that clinically depressed patients with borderline features have a high prevalence (75070) of neuroendocrine abnormalities independent of meeting DSM II! criteria for major depressive disorder. When used alone, the DST identified 54°70 of such patients (Table I); in combination, the DST and TRH test were abnormal in 75070 of these borderline women. Our findings of a large number of
462
HarvEY A. STERNBACHet al.
a b n o r m a l D S T s in b o r d e r l i n e s a r e in a g r e e m e n t w i t h t h e r e s u l t s o f C a r r o l l e t al. ( 1 9 8 1 a ) w h o r e p o r t e d a n a b n o r m a l D S T in 13 o f 21 p a t i e n t s w i t h b o r d e r l i n e d i s o r d e r . T h e s e f i n d i n g s , in c o n j u n c t i o n w i t h r e p o r t s o f r e d u c e d R E M l a t e n c y in b o r d e r l i n e p a t i e n t s ( A k i s k a l , 1981) a n d a h i g h r a t e o f a f f e c t i v e illness in t h e f a m i l i e s o f s u c h p a t i e n t s ( S t o n e , 1977, 1979), s u p p o r t t h e c o n c e p t o f b o r d e r l i n e d i s o r d e r s b e i n g m o r e closely r e l a t e d to a f f e c t i v e r a t h e r t h a n t o s c h i z o p h r e n i c illness. F u r t h e r , t h e p r e s e n c e o f a l a r g e n u m b e r o f n e u r o e n d o c r i n e a b n o r m a l i t i e s in b o r d e r l i n e p a t i e n t s s u g g e s t s t h a t m a n y s u c h p a t i e n t s m i g h t b e r e s p o n s i v e t o t r e a t m e n t w i t h l i t h i u m a n d / o r a n t i d e p r e s s a n t s ( K l e i n , 1975; A k i s k a l e t al., 1979). W e b e l i e v e f u t u r e s t u d i e s o f b o r d e r l i n e p a t i e n t s s h o u l d b e c o n d u c t e d in s u c h a m a n n e r as t o i n c l u d e all p a t i e n t s w i t h b o r d e r l i n e f e a t u r e s i n d e p e n d e n t o f t h e i r f u l f i l l i n g D S M I l l c r i t e r i a f o r m a j o r d e p r e s s i v e d i s o r d e r . I f a s i g n i f i c a n t p e r c e n t a g e o f all s u c h p a t i e n t s w e r e t o h a v e n e u r o e n d o c r i n e a b n o r m a l i t i e s , s u c h as we h a v e r e p o r t e d h e r e , this w o u l d p r o v i d e increasing evidence for the affective nature of some patients' borderline disorders. Studies e x a m i n i n g D S T a n d T R H test a b n o r m a l i t i e s in b o r d e r l i n e s w i t h r e f e r e n c e t o r e s p o n s e t o pharmacotherapy for depression need to be performed.
REFERENCES AKISkAI, H. S. (1981) Subaffeclive disorders: Dysthymic, cyclothymic and bipolar I1 disorders in the "borderline" realm. Ps),chial. din. N. Am. 4, 25-46. AkisK,xl, H. S., KHANI, M. & S(OTT-StrAUSS, A. (1979) Cyclothymic temperamental disorders. Psvehiat. elm. N. Am. 2, 527-554. AMERICAN PSYCHIATRI( ASSO(IATION (1980) Diagnostic attd Statistical Manual o f Mental Disorders, Third Edition (DSM-III). American Psychiatric Association, Washington, D.C. Carroll,
B. J., GrEDEN, J. F., FeINBErc;, M., LoHr, N., J,xMEs, N. M., Sruintr, M., HAsKt. t t , R. F.,
Att3AIA, A. A., D~VJ(;Ne, J. P. & TArtKA, J. (1981a) Neuroendocrine evaluation ot" depression in borderline patients. Psychiat. clin. N. Am. 4, 89-99. C A r r o t l , B. J., FEINBERG, M., GrFDEN, J. F., TARIKA, J., AI BAI .x, A. A., H a s k t t l , R. F., JaMes, N. M.,
Kront-ol, Z., LoHr, N., Stexner, M., DEVIGNE, J. P. & YOL NG, E. (1981b) A specific laboratory test for the diagnosis of melancholia. Arehs gen. P~vehiat. 38, 15 22. DONAHL'e, J. & SGONTAS, D. (1975) Improved radioimmunoassay of plasma cortisol. Clin. Chem. 21,770. ExteIN, 1., POTTASH, A. L. C. & GOLD, M. S. (1981) The thyrotropin-releasing hormone test in the diagnosis of unipolar depression. Psychiat. Res. 5,311-316. GolD, M. S., POTTASH, A. L. C., EXTEIN, I. & S~'I:ENe~, D. R. II981) Diagnosis of depression in the 1980"s. J. A m . Med. Ass. 245, 1562- 1564. GUNDErson, J. G. & StNc;ur, M. T. (1975) Defining borderline patients: and overview..4m. J. P.sychzat. 132, 1 10. H a l l , R., AMOS, J. & ORMSTON, B. (1971) Radioimmunoassay of human serum thyrotropin. Br. Med. J. I, 582. KIrKeGAArD, C. (1981) The thyrotropin response to thyrotropin releasing hormone in endogenous depression. Psychoneuroendoerinology 6, 189 - 212. K1 eln, D. F. (1975) Psychopharmacology and the borderline patient. In Borderline States in P.Evchioto'. J. E. Mack(Ed.), pp. 75 91.Grnne&Stratlon, New York. I.OO~.I-N, P. T. & PRAN(;E, Jr A. J. (1982) Serum thyrotropin response to thyrotropimreleasing hormone in psychiatric patients: a review. Atn. J. Psvchiat. 139, 405 -416. STERNBA(H, H. A., EXTEIN, 1., POTTASH, A. C. & GolD, M. S. (1982) Thyrotropin-releasing hormone. N e w Engl. J. Med. 306, 1489. STONe, M. H. (1977) The borderline syndrome: evolution of the term, genetic aspects and prognosis. Am. J. Psvehother. 31,345 -365. SIONF, M. H. (1979) Contemporary shift in the borderline concept from a subschizophrenic disorder to a subaffeclive disorder. Psvchiat. elin. N. Am. 3, 577 - 594.
462, 1983.
0306 - 4 5 3 0 / 8 3 $ 3 . 0 0 + 0 . 0 0 ~ 1983 P e r g a m o n Press Ltd.
P r i n l e d in (,ireat B r i t a i n .
SHORT COMMUNICATION THE D E X A M E T H A S O N E S U P P R E S S I O N A N D T H Y R O T R O P I N - R E L E A S I N G H O R M O N E TESTS IN DEPRESSED BORDERLINE PATIENTS HARVEY A. STERNBACH,*:~ JAN FLEMING, II IRL EXTEIN,* A. L. C. POTTASH*~ and MARK S. GOLD*'t *Fair Oaks Hospital and the ~Psychiatric Diagnostic Laboratories of America Summit, NJ; :l:Department of Psychiatry, West Los Angeles VA Medical Center, Brentwood Division. and UCLA-Neuropsychiatric Institute, Los Angeles; §Falkirk Hospital, Central Valley, NY; and the IIUniversity of Toronto, Faculty of Medicine, Toronto, Canada
(Received 15 October 1982; in final form 15 I"ebruao' 1983) SUMMARY Borderline patients can be both a diagnostic and a therapeutic enigma. We investigated a group of 24 depressed women with borderline personality disorder or strong borderline features by DSM 111 criteria for the presence of either an abnormal dexamethasone suppression test (DST) or a blunted TSH response to TRH, abnormalities which have been reported in major depression. Thirteen of the 24 borderlines failed to suppress on the DST, compared with one of 14 normal women (p < 0.01). Nine of the 24 borderlines had a blunted TSH response to TRH, compared with one of 11 normal women. Neuroendocrine abnormalities were found in a total of 75°/0 of the borderline women, independent of whether or not they met DSM 111 criteria for major depressive disorder. The results of this study support the notion that many borderline patients with depression have a genuine affective component to their illness, perhaps biologically similar to major depression in non-borderlines. INTRODUCTION THE DIAGNOSIS and t r e a t m e n t o f the " b o r d e r l i n e " patient is o n e o f the most difficult and c o n t r o v e r s i a l areas o f psychiatry. B o r d e r l i n e disorders are generally expressed in c h a r a c t e r o l o g i c a l terms and d e f i n e d by various traits such as a f f e c t i v e instability, impulsivity, identity disturbance, intense interpersonal relationships (American Psychiatric A s s o c i a t i o n , 1980), and even b r ie f psychotic episodes ( G u n d e r s o n & Singer, 1975). W h e n such patients c o m p l a i n o f feeling depressed, their d y sp h o r i c m o o d state is usually c o n s i d e r e d to be " n e u r o t i c " in n a t u r e and o f t en i n t er p r et ed in p s y c h o a n a l y t i c terms. C a r r o l l et al. (1981a) recently have reviewed s o m e o f the diagnostic difficulties in assessing patients with b o r d e r l i n e disorders, and A ki sk al (1981) has reviewed the rationale b e h i n d c o n s i d e r i n g b o r d e r l i n e disorders in the realm o f a " s u b a f f e c t i v e " rather than a " s u b s c h i z o p h r e n i c " illness. T h e cortisol response to d e x a m e t h a s o n e and the t h y r o t r o p i n ( T S H ) response to t h y r o t r o p i n - r e l e a s i n g h o r m o n e ( T R H ) have been s h o w n to be useful diagnostic aids in the e v a l u a t i o n o f e n d o g e n o m o r p h i c depression (Carroll et al., 1981b; G o l d et al., 1981; K i r k e g a a r d , 1981; L o o s e n & P r a n g e , 1982; S t e r n b a c h et al., 1982). Decisions regarding the t r e a t m e n t o f b o r d e r l i n e patients with either a n t i d ep r essan t s or lithium could be aided by the presence o f a biological m a r k e r such as an a b n o r m a l d e x a m e t h a s o n e suppression Address correspondence to: Dr. Harvey Sternbach, Brentwood V. A. Medical Center, 11301 Wilshire Blvd., Los P.ngeles, CA 90073, U.S.A. 459
460 test ( D S T ) o r T R H D S T s in 13 o f endogenomorphic We report here
HARVEY A. STERNBACHet al. test. C a r r o l l e t a l . ( 1 9 8 1 a ) h a v e r e p o r t e d o n t h e p r e s e n c e o f a b n o r m a l 21 b o r d e r l i n e patients, consistent with such patients having depression. t h e r e s u l t s o f a n i n v e s t i g a t i o n o f n e u r o e n d o c r i n e a b n o r m a l i t i e s in 24
w o m e n w i t h f e a t u r e s o f b o r d e r l i n e p e r s o n a l i t y d i s o r d e r b y D S M 111 c r i t e r i a . T h e r e s u l t s o f this study indicate that such women are clinically and neuroendocrinologically similar to p a t i e n t s w i t h m a j o r d e p r e s s i v e d i s o r d e r b y D S M II1 c r i t e r i a . PATIENTS AND METHODS Subjects for this study consisted of 24 women, age range 14-54 yrs, mean age _+ S.D. ~ 27.7 + 10.1, consecutively admitted to Fair Oaks Hospital's Neuropsychiatric Evaluation Unit ~ith a diagnosis of borderline personality disorder or borderline personality features. Thirteen of these women fulfilled strict DSM-III criteria for borderline personality disorder (five or more of the eight criteria), while the remaining I 1 patients met four of eight criteria and were categorized by the authors as having "mixed" personality disorders with strong borderline features. None of the 24 patients had abused drugs or alcohol for at least one month prior to admission. All patients had normal physical examinations and routine laboratory testing, and none had taken within the previous week medications that would interfere with the DST or TRH tests (e.g. barbiturates, aspirin, thyroid hormone, etc.L All 24 patients underwent systematic neuroendocrine evaluation with the 1 mg dexamethasone suppression test (Carroll el al., 1981b) and the 500 ~.g TRH test (Extein et al., 1981). In all cases, patients first had the TRH test, followed at least one, but no more than three days later by the DST. None of the 24 patients had abnormal basal thyroid function tests (TSH, T3 uptake, T3 RIA, T4). For the TRH test, serum TSH was measured by radioimmunoassay (Hall et al., 1971) at 0, 15, 30, 60 and 90 rain after TRH injection at 0900 hr. The Lx max TSH (peak TSH minus baseline) was calculated for each patient. Any patient with a A max TSH < 7 talU ml was considered to have a blunted TSH response to TRH (Extein et al., 1981). For comparison, we used an agedmatched control group of 11 normal volunteer women ~ho, on inter~ie~, had no personal or family history of psychiatric illness and who consented to TRH testing (mean age 31.9 _+9.0 yrs). For the DST, patients were given dexamethasone (1 mg p.o.) at 2300 hr with serum collected at 0800, 120(I. 160(I and 2355 hr the next day, serum cortisol was measured in duplicate by radioimmunoassay (Donahue & Sgontas, 1975). Any cortisol concentration >~ 5 ~tg/dl was considered to be non-suppression (Carroll el al., 198l b). For comparison ~e used an age-matched control group of 14 normal vohmteer ~omen ~ho, by intervie~, had no personal or famib history of psychiatric illness and who consented to have the DST (mean age 28.6 + 5.6 yrs). Statistical analysis was performed with the Fisher exact test, Student's t-test and chi-square test, as appropriate. RESULTS T a b l e I i n d i c a t e s t h a t , o f t h e 24 b o r d e r l i n e p a t i e n t s s t u d i e d , 17 ( 7 1 % ) m e t D S M i l l c r i t e r i a f o r m a j o r d e p r e s s i v e d i s o r d e r , a n d t h e r e m a i n i n g s e v e n p a t i e n t s all h a d d e p r e s s i v e f e a t u r e s . T h e r e w a s n o s i g n i f i c a n t d i f f e r e n c e in a g e b e t w e e n t h o s e p a t i e n t s w i t h ( 2 9 . 0 _+ 10 yrs), a n d w i t h o u t ( 2 4 . 4 _+ 7.8 yrs), m a j o r d e p r e s s i v e d i s o r d e r (I = 1.11, p = ns). E l e v e n o f t h e 17 p a t i e n t s ( 6 5 % ) m e e t i n g c r i t e r i a f o r m a j o r d e p r e s s i v e d i s o r d e r h a d a n a b n o r m a l DST, while 2 of 7 patients (29%) without major depression also had an abnormal DST. O n t h e T R H test, 7 o f 17 p a t i e n t s ( 4 1 % } w i t h m a j o r d e p r e s s i o n h a d a b l u n t e d T S H response to TRH, while 2 of 7 patients (29%) without major depression had such a r e s p o n s e . A l t h o u g h t h e r e w a s a t r e n d f o r a h i g h e r p r o p o r t i o n o f n o n - s u p p r e s s o r s in borderlines with major depression, there was no significant difference between those patients with and without major depression with regard to the presence of an abnormal D S T o r T R H test ( F i s h e r e x a c t test, p = 0 . 1 0 a n d p = 0 . 3 1 , r e s p e c t i v e l y ) . F u r t h e r , t h e r e w a s n o s i g n i f i c a n t d i f f e r e n c e in D S T o r T R H test a b n o r m a l i t i e s b e t w e e n t h e 13 p a t i e n t s w h o m e t five o f e i g h t D S M 111 c r i t e r i a f o r b o r d e r l i n e p e r s o n a l i t y d i s o r d e r (10 h a v i n g major depression) and the I 1 patients meeting four of eight DSM-III criteria for the same d i s o r d e r ( s e v e n w i t h m a j o r d e p r e s s i o n ) F i s h e r e x a c t test, p = 0 . 1 4 . T h e r e w a s n o
D S T AND T R H
IN BORDERLINE PERSONAtITY
461
TABLE [. DEXAMETHASONE SUPPRESSION TEST ( D S T ) AND T S H RESPONSES TO T R H
Patient
Age
I 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
19 36 22 39 54 33 33
36 24 14 24 27 37 16 40 20 19 26 15 19 31 37 25 18
IN BORDERLINE PATIENTS
DSM-III borderline criteria m e t
Depression: major vs non-major
Abnormal DST
Blunted ix m a x T S H
5 5 5 4 4 4 5 6 5 5 4 5 4 5 4 4 5 5 5 4 4 5 4 4
M M M M M M M M M M M M M M M M M NM NM NM NM NM NM NM
+ + + + + + + + + + + + + -
+ + + + + + + + + -
significant difference in age between DST suppressors and non-suppressors (26.0 _+ 12.0 vs 29.1 _+ 8.6 yrs, respectively) or the blunted vs normal TSH responders (30.3 _+ 10.9 vs 26. l _ 9.4 yrs, respectively). Of further note is the finding that, of the 13 patients with an abnormal DST, an elevated cortisol was found at 20 of a possible 52 time points: there were no abnormal cortisol values at 0800 hr, three abnormal values at 1200 hr, eight elevated cortisol levels at 1600 hr, and nine such elevated levels at 2355 hr. When we compared these borderline patients as a group with the normal female volunteers, there was a statistically significantly higher prevalence of DST nonsuppressors in the borderlines (17 of 24) compared with the normals (1 of 14) (X 2 = 9.91, df = l, p < 0.01). There was a non-significant trend for the borderline group to have more blunted TSH responses (9 of 24) compared with the normals (1 of I l) (X 2 = 2.95, df = I, p < 0.10). As a group, 18 of the 24 borderline patients (75070) had at least one neuroendocrine abnormality. DISCUSSION
The results of this preliminary investigation indicate that clinically depressed patients with borderline features have a high prevalence (75070) of neuroendocrine abnormalities independent of meeting DSM II! criteria for major depressive disorder. When used alone, the DST identified 54°70 of such patients (Table I); in combination, the DST and TRH test were abnormal in 75070 of these borderline women. Our findings of a large number of
462
HarvEY A. STERNBACHet al.
a b n o r m a l D S T s in b o r d e r l i n e s a r e in a g r e e m e n t w i t h t h e r e s u l t s o f C a r r o l l e t al. ( 1 9 8 1 a ) w h o r e p o r t e d a n a b n o r m a l D S T in 13 o f 21 p a t i e n t s w i t h b o r d e r l i n e d i s o r d e r . T h e s e f i n d i n g s , in c o n j u n c t i o n w i t h r e p o r t s o f r e d u c e d R E M l a t e n c y in b o r d e r l i n e p a t i e n t s ( A k i s k a l , 1981) a n d a h i g h r a t e o f a f f e c t i v e illness in t h e f a m i l i e s o f s u c h p a t i e n t s ( S t o n e , 1977, 1979), s u p p o r t t h e c o n c e p t o f b o r d e r l i n e d i s o r d e r s b e i n g m o r e closely r e l a t e d to a f f e c t i v e r a t h e r t h a n t o s c h i z o p h r e n i c illness. F u r t h e r , t h e p r e s e n c e o f a l a r g e n u m b e r o f n e u r o e n d o c r i n e a b n o r m a l i t i e s in b o r d e r l i n e p a t i e n t s s u g g e s t s t h a t m a n y s u c h p a t i e n t s m i g h t b e r e s p o n s i v e t o t r e a t m e n t w i t h l i t h i u m a n d / o r a n t i d e p r e s s a n t s ( K l e i n , 1975; A k i s k a l e t al., 1979). W e b e l i e v e f u t u r e s t u d i e s o f b o r d e r l i n e p a t i e n t s s h o u l d b e c o n d u c t e d in s u c h a m a n n e r as t o i n c l u d e all p a t i e n t s w i t h b o r d e r l i n e f e a t u r e s i n d e p e n d e n t o f t h e i r f u l f i l l i n g D S M I l l c r i t e r i a f o r m a j o r d e p r e s s i v e d i s o r d e r . I f a s i g n i f i c a n t p e r c e n t a g e o f all s u c h p a t i e n t s w e r e t o h a v e n e u r o e n d o c r i n e a b n o r m a l i t i e s , s u c h as we h a v e r e p o r t e d h e r e , this w o u l d p r o v i d e increasing evidence for the affective nature of some patients' borderline disorders. Studies e x a m i n i n g D S T a n d T R H test a b n o r m a l i t i e s in b o r d e r l i n e s w i t h r e f e r e n c e t o r e s p o n s e t o pharmacotherapy for depression need to be performed.
REFERENCES AKISkAI, H. S. (1981) Subaffeclive disorders: Dysthymic, cyclothymic and bipolar I1 disorders in the "borderline" realm. Ps),chial. din. N. Am. 4, 25-46. AkisK,xl, H. S., KHANI, M. & S(OTT-StrAUSS, A. (1979) Cyclothymic temperamental disorders. Psvehiat. elm. N. Am. 2, 527-554. AMERICAN PSYCHIATRI( ASSO(IATION (1980) Diagnostic attd Statistical Manual o f Mental Disorders, Third Edition (DSM-III). American Psychiatric Association, Washington, D.C. Carroll,
B. J., GrEDEN, J. F., FeINBErc;, M., LoHr, N., J,xMEs, N. M., Sruintr, M., HAsKt. t t , R. F.,
Att3AIA, A. A., D~VJ(;Ne, J. P. & TArtKA, J. (1981a) Neuroendocrine evaluation ot" depression in borderline patients. Psychiat. clin. N. Am. 4, 89-99. C A r r o t l , B. J., FEINBERG, M., GrFDEN, J. F., TARIKA, J., AI BAI .x, A. A., H a s k t t l , R. F., JaMes, N. M.,
Kront-ol, Z., LoHr, N., Stexner, M., DEVIGNE, J. P. & YOL NG, E. (1981b) A specific laboratory test for the diagnosis of melancholia. Arehs gen. P~vehiat. 38, 15 22. DONAHL'e, J. & SGONTAS, D. (1975) Improved radioimmunoassay of plasma cortisol. Clin. Chem. 21,770. ExteIN, 1., POTTASH, A. L. C. & GOLD, M. S. (1981) The thyrotropin-releasing hormone test in the diagnosis of unipolar depression. Psychiat. Res. 5,311-316. GolD, M. S., POTTASH, A. L. C., EXTEIN, I. & S~'I:ENe~, D. R. II981) Diagnosis of depression in the 1980"s. J. A m . Med. Ass. 245, 1562- 1564. GUNDErson, J. G. & StNc;ur, M. T. (1975) Defining borderline patients: and overview..4m. J. P.sychzat. 132, 1 10. H a l l , R., AMOS, J. & ORMSTON, B. (1971) Radioimmunoassay of human serum thyrotropin. Br. Med. J. I, 582. KIrKeGAArD, C. (1981) The thyrotropin response to thyrotropin releasing hormone in endogenous depression. Psychoneuroendoerinology 6, 189 - 212. K1 eln, D. F. (1975) Psychopharmacology and the borderline patient. In Borderline States in P.Evchioto'. J. E. Mack(Ed.), pp. 75 91.Grnne&Stratlon, New York. I.OO~.I-N, P. T. & PRAN(;E, Jr A. J. (1982) Serum thyrotropin response to thyrotropimreleasing hormone in psychiatric patients: a review. Atn. J. Psvchiat. 139, 405 -416. STERNBA(H, H. A., EXTEIN, 1., POTTASH, A. C. & GolD, M. S. (1982) Thyrotropin-releasing hormone. N e w Engl. J. Med. 306, 1489. STONe, M. H. (1977) The borderline syndrome: evolution of the term, genetic aspects and prognosis. Am. J. Psvehother. 31,345 -365. SIONF, M. H. (1979) Contemporary shift in the borderline concept from a subschizophrenic disorder to a subaffeclive disorder. Psvchiat. elin. N. Am. 3, 577 - 594.