Psychiutry Research, 9, 107-I 13 Elsevier

107

The TRH Test in Patients With Borderline Personality Disorder

James C. Garbutt, PeterT. Loosen, Alan Tipermas, and Arthur J. Prange, Jr.

Received November 3, 1982; revised version received February 14, 1983; accepted April 20, 1983.

Abstract. Fifteen patients with a primary diagnosis of borderline personality disorder were studied with the thyrotropin-releasing hormone (TRH) test. Twelve carried the additional diagnosis of depression, substance abuse, or both. A blunted thyroid-stimulating hormone (TSH) response to TRH was found in seven patients, two of whom were neither depressed nor had the additional diagnosis of depression

and/ or substance abuse. TSH blunting was unrelated to such factors as thyroid status, serum cortisol, weight, height, or body surface. Since TSH blunting occurs in about 25% of patients with major depression but not in schizophrenia, the findings suggest that some patients with borderline personality disorder share a neuroendocrine abnormality with some affective disorder patients.

Key Words. TRH test, borderline personality disorder, depression.

In recent years, the syndrome identified as borderline personality disorder has attracted considerable interest in psychiatry. The forerunners of this syndrome can be traced back to diagnoses such as pseudoneurotic schizophrenia, latent schizophrenia, borderline schizophrenia, and “as-if” personality (Kernberg, 1975). Although these diagnoses represented descriptive attempts to define patients who were on the “border” between psychosis and neurosis, some ambiguity remained. Several authors have therefore attempted to define the borderline personality disorder syndrome operationally (Grinker et al., 1968; Spitzer et al., 1979; Perry and Klerman, 1980; Gunderson et al., 1981). Their studies have demonstrated the syndrome’s complexity while also pointing out the discriminating features which separate borderline patients from patients with other disorders such as schizophrenia or depression. However, depression is often observed in borderline patients (Stone, 1980) and there is a greater incidence of depression in the relatives of borderline patients compared to the relatives of schizophrenic patients (Loranger et al., 1982). These data, of course, suggest that patients with borderline personality disorder may be more closely linked to the affective disorders than to the schizophrenia syndrome.

James C. Garbutt. M.D., is with the Clinical Research Unit, Dorothea Dix Hospital, Raleigh, NC, USA. Peter T. Loosen, M.D., is Associate Professor of Psychiatry, University of North Carolina, School of Medicine, Chapel Hill, NC, USA. and Director of the Clinical Research Unit, Dorothea Dix Hospital, Raleigh, NC, USA. Alan Tipermas. M.D.. is now a resident at the New York Hospital, Cornell Medical Center, Westchester Division, White Plains, NY, USA. Arthur J. Prange. Jr., M.D., is Professor of Psychiatry, University of North Carolina, School of Medicine, Chapel Hill, NC. USA. (Reprint requests to Dr. J.C. Garbutt. Clinical Research Unit. Dorothea Dix Hospital, Edgerton Building, Raleigh, NC 2761 I, USA.)

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108

The thyrotropin (thyroid-stimulating hormone, TSH) response to thyrotropin- releasing hormone (TRH) (the TRH test) has been found to be useful as a potential marker for depression (Loosen and Prange, 1982). Forty-eight studies involving more than 1,100 patients have shown that about 25% of depressed patients have a blunted TSH response to TRH. Although TSH blunting seems not to be specific for depression-it has also been observed in some alcoholic patients (Loosen et al., 1979)-it has not been seen in schizophrenic patients (Loosen and Prange, 1982). We here report findings on the TRH test in patients with borderline personality disorder.

Methods

Fifteen patients with the diagnosis of borderline personality disorder according to the Diag- nostic and Statistical Manual of Mental Disorders (DSM-III) (American Psychiatric Associa- tion, 1980) and the Diagnostic Interview for Borderline (DIB) (Gunderson et al., 1981) were included in the study. There were nine men and six women. Their mean (+ SD) age was 28 * 7 years. Each patient was first seen independently by at least two psychiatrists (JCG, PTL, AT). Diagnoses were then submitted to a diagnostic conference which made the final consensus diagnosis using DSM-IIIcriteria without knowledge of the results of the TRH test. Twelve of 15 patients carried DSM-III Axis I diagnoses in addition to the diagnosis of borderline personality (Table 1). These diagnoses fell into the category of affective disorders, substance abuse, or both. The DlB was completed by direct interview in 5 patients while the retrospective DIB scale was used in the remaining 10 patients. The DIB scores are given in Table 1. The Hamilton Rating Scale for Depression (HRS) (Hamilton, 1960) was completed on 12 patients on the day of infusion.

Fifteen age- and sex-matched normal volunteers were used for comparison. Their mean (* SD) age was 3 1 f 6 years. Normal volunteers were screened in a psychiatric interview by one or more of the authors and did not meet criteria for any DSM-III diagnosis. All had a HRS total score (items I-17) below 5 before injection of TRH.

None of the patients and subjects presented historical, chemical, or physical evidence of any endocrine disorder or other major somatic illness. Normal subjects were not taking any medications including oral contraceptives. Patients underwent a drug-free period of at least 10 days whenever necessary and were not taking oral contraceptives. None had taken lithium within the previous 6 months. Family histories of patients and subjects were taken using the Research Diagnostic Criteria (RDC) (Spitzer et al., 1977). In most cases the family histories were based on the interview with the patients.

The TRH test was completed according to our standard procedure (Loosen and Prange, 1982). All patients and subjects received TRH, 500 pg over 1 minute, at 9:00 a.m. after an overnight fast. Blood was taken twice before and 30, 60, 90, and 180 minutes after TRH injection. Serum samples were frozen at -20°C until assayed in duplicate. Baseline data reported are the averages of results from samples obtained at -15 and 0 minutes. For response data, we used the highest level (peak) after TRH injection while Amax gives the maximum rise over respective baselines. TSH levels were measured with a modification of the double antibody radioimmunoassay (RIA) procedure of Ode11 et al. (1967). The intra-assay coefficient of variance (CV) was 5.2%. Prolactin (PRL) levels were determined by a double antibody RIA method (Hwanget al., 197 1). The method yielded an intra-assay CV of 8.5%. Growth hormone (GH) levels (intra-assay CV: 4.2%) were measured with a modification of the RIA of Gordon and Roth (1971).‘~-Triiodothyronine (T,) was measured with a modification of the RIA procedure first proposed by Pilleggi et al. (1972). The method yielded an intra-assay CV of 5%. Free thyroxine (FT.,)-index was estimated using I 125-T to determine unoccupied thyroid binding globulin sites (T,-uptake) and by measuring total T, by the Murphy-Pattee competitive binding principle (Hales et al., 1972). The FT,-index was calculated from these two measures. Over a broad range the FT.,-index is proportional to free (unbound, active) T,. Cortisol was measured

Tab

le

1. P

atie

nt

char

acte

rist

ics

Pat

ien

t #

Ag

e T

SH

F

amily

S

ex

DS

M-I

II A

xis

I d

iag

no

sis’

D

IB s

core

* H

RS

b

lun

tin

g

his

tory

3

1 23

F

2 22

F

3 23

F

4 5 6 31

F

7 36

M

a 30

M

9 29

M

10

28

M

11

37

M

12

41

M

13

20

M

14

40

M

15

18

M

19

F

29

F

Non

e

Non

e

Dys

thym

ic

diso

rder

, m

ixed

su

bsta

nce

abus

e

Maj

or

depr

essi

on,

bulim

ia

Dys

thym

ic

diso

rder

, al

coho

l

abus

e,

seda

tive-

hypn

otic

ab

use

Bip

olar

di

sord

er,

depr

esse

d

Non

e

Maj

or

depr

essi

on,

alco

hol

abus

e

Alc

ohol

ab

use

Dys

thym

ic

diso

rder

Maj

or

depr

essi

on,

alco

hol

abus

e

Maj

or

depr

essi

on

Maj

or

depr

essi

on

Maj

or

depr

essi

on,

alco

hol

depe

nden

ce

Maj

or

depr

essi

on,

alco

hol

6 6

Yes

4

Yes

19

8 10

N

o N

one

9 29

N

o

A,

D

Ye

s

Ye

s

Ye

s

9 9

Yes

Yes

Yes

Ye

s

Yes

8 N

o

Non

e

8 Ye

s A

27

Yes

A/D

11

No

A

24

Ye

s A

16

Yes

A

, D

N/A

Y

es

A

N/A

Ye

s N

one

N/A

N

o

A

0 N

o

Yes

A

dopt

ed

No

S

No

D,

A

A

abus

e in

rem

issi

on

1. A

ll pa

tient

s ha

d th

e pr

inci

pal

diag

nosi

s of

bor

derli

ne

pers

onal

ity

diso

rder

on

DS

M-/

/I A

xis

II.

2. Y

es r

efer

s to

tho

se

patie

nts

who

w

ere

iden

tifie

d as

bor

derli

ne

by t

he

retr

ospe

ctiv

e D

IE

code

. 3.

A =

alc

ohol

ism

, D

= d

epre

ssio

n,

and

S =

sch

izop

hren

ia.

110

with a modification of the RlA method described by Campuzano et al. (1973). The intra-assay CV was 4.7%.

Results

Mean baseline TSH, maximum TSH response, and Amax TSH were significantly reduced in patients (Table 2). Furthermore, 7 of 15 patients, but none of the normal subjects, had a blunted TSH response (Amax TSH < 5 PU /ml). McNemar’s test for matched pairs showed this difference to be significant (p <O.Ol). Body weight, height, and body surface did not account for these differences (Table 2).

Baseline prolactin, growth hormone, total T,, FT,-index, T,, T,-uptake, and cor- tisol were normal in patients (Table 2). Their prolactin responses also were normal.

Comparison of patients with TSH blunting to patients without such blunting revealed no significant differences in baseline TSH, prolactin, growth hormone, total T,. FT,-index, T,, T,-uptake, and cortisol (data not shown).

Evaluation of family histories revealed that 10 of 15 patients had first-degree relatives with alcoholism, 4 of 15 with major affective disorder, and 1 of 15 with schizophrenia (Table 1). Two of 15 normal subjects had first-degree relatives with suicide attempts; none, however, had a family history of alcoholism or schizophrenia.

Discussion

In a group of patients with borderline personality identified by the criteria of DSM-III

and the DIB, we have shown that a significant number demonstrated a blunted TSH response to TRH. This finding has been reported to occur in a variety of psychiatric conditions, namely depression and alcoholism (Loosen and Prange, 1982). Since the majority of our patients carried diagnoses of alcoholism and/ or affective disorder, it is possible that these diagnoses may have accounted for TSH blunting. For example, five of seven patients with TSH blunting had the additional diagnosis of depression or alcoholism. This high incidence of depression and alcoholism was probably due to two factors. First, the population presented here consisted of inpatients who were either more disturbed or in the midst of a crisis. Secondly, mood disturbances and/or alcohol abuse are common criteria for the diagnosis of borderline personality in both DSM-IIZand the DIB. Therefore, it is not surprising that many patients with border- line personality, especially while hospitalized, also meet DSM-IIIcriteria for affective disorders and; or alcohol abuse. In fact, DSM-III directly acknowledges this (DSM-

111, p. 322). This phenomenon has also been noted by other authors (Akiskal, 1981; Stone. 1981). However, two patients with TSH blunting were neither acutely depressed nor had they received diagnoses of affective disorders or alcoholism. This suggests that some borderline patients share TSH blunting with some depressed and alcoholic patients. However, prospective studies of nondepressed and nonalcoholic borderline patients are needed before any definite conclusion regarding the signifi- cance of this finding can be drawn. The finding does, however, have a certain degree of specificity since TSH blunting has not yet been observed in schizophrenic patients (Loosen and Prange. 1982).

111

Table 2. Endocrine findings in patients and subjects (mean k SD)

Patients (n = 15)

Age Weight, pounds

Height, inches

Body surface, units

TSH (pU/ml)

Base

Peak

AMax

Prolactin (ng/mll

Base

Peak

AMax

Growth hormone (ng/ml)

Base

FT,-index (units)

Base

Peak

AMax

Total T, (Fg/dl)

Base

Peak

AMax

Total T, (ng/dl I Base Peak

AMax

T,U, %

Base

Cortisol (pg/dl)

Base

20 27

149.7 + 37.9

66.6 * 6.2

1.84? 0.19

2.6 f 0.81

10.6 + 4.81

7.0 f 4.01

6.6 f 3.0

27.5 ? 8.3

21.0 * 7.7

2.0 ? 1.4

6.7 2 1.6

8.3 f 1.7

1.5 * 0.7

6.7 f 1.6

6.1 ? 1.6

1.4 * 0.9

148.1 f 51.3

191.3 f64.3

43.2 2 29.9

49.4 ? 5.1

12.7 -t 4.4

Normal subjects (n= 15)

31 f 6

173.4 It 25.2

66.9 f 3.9

I.942 0.15

3.5 * 1.3

15.3 * 5.5

11.8 2 5.3

8.0 f 4.3

37.8 t 18.7

29.8 ? 17.4

2.5 ? 2.6

7.0 2 1.2

8.1 * 0.9

1.0 * 1.1

7.0 f 1.4

8.2 + 1.1

1.0 + 1.0

134.8 * 40.1

179.3 f 41 .O

38.9 f 36.3

48.6 + 3.6

12.4 ? 9.2

1. p c 0.05. Student’s t test

There is increasing evidence that borderline patients share common features wit}. some depressed patients. This evidence has come from studies examining family and personal history, as well as biological markers other than the TRH test.

Three reports have described a high familial incidence of affective disorders in first-degree relatives of borderline patients. Stone (1980) found a significantly higher rate of affective disorders in relatives of borderline patients than in relatives of

112

schizophrenic patients. Liebowitz and Klein (1981) reported a high incidence of affective disorders in families of patients with the diagnosis of hysteroid dysphoria, many of whom met DSM-III criteria for borderline disorder. Loranger et al. (1982) studied 83 female patients with a clear DSM-IZZ diagnosis of borderline personality disorder. Patients were compared to 100 female bipolar patients and 100 female schizophrenic patients. Borderline patients had a significantly higher familial inci- dence of unipolar depression and borderline personality if compared to schizophrenic patients or to the expected incidence in the general population. Here it is worth noting that our patients also had a high familial incidence of depression and alcoholism but not of schizophrenia.

In addition to TSH blunting, two other biological markers have been associated with the affective disorders: cortisol nonsuppression after dexamethasone (Carroll et al., 198 1 a) and a shortened rapid eye movement (REM) latency during sleep (Kupfer et al., 1978). Carroll et al. (198 1 b) administered the dexamethasone suppression test (DST) to 21 patients with borderline personality disorder. Thirteen patients were cortisol nonsuppressors; only eight of them had received RDC diagnoses of major depression. Reus (1982) also recently reported DST nonsuppression in borderline patients without major depression. In regard to REM latency, Akiskal(l981) studied patients with borderline personality disorder, primary affective disorder, and nonaf- fective personality disorder. Patients with borderline personality disorder and pri- mary affective disorder had a significantly decreased REM latency. Futhermore, the borderline patients were not clinically depressed. Kupfer (personal communication) also found shortened REM latency in some borderline patients.

In summary, our data suggest that some patients with borderline personality disorder share TSH blunting with some depressed (or alcoholic) patients. Other groups using different biological markers (Carroll et al., 198 16; Reus, 1982; Kupfer, personal communication) or epidemiological data(Stone, 1980; Akiskal, 1981; Stone, 1981; Loranger et al. 1982) have also reported commonalities between borderline personality and depression. Whether borderline personality disorder is a variant of the affective disorders, or a separate disorder which shares biological markers with the affective disorders awaits further study.

Acknowledgments. The authors would like to thank Dr. John G. Gunderson for his com- ments and Ms. Kathy Ayers for manuscript preparation.

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