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Koenigsberg et al. DEPRESSION AND ANXIETY 10:158–167 (1999)
RELATIONSHIP BETWEEN DEPRESSION AND
BORDERLINE PERSONALITY DISORDER
Harold W. Koenigsberg, M.D.,* Iseoma Anwunah, M.D., Antonia S. New, M.D.,Vivian Mitropoulou, M.A.,
Frances Schopick, M.S.W., and Larry J. Siever, M.D.
The frequent occurrence of depressive symptoms in patients with borderline
personality disorder has generated considerable interest in the nature of the
relationship between borderline personality disorder and the depressive disor-
ders. Data from the perspectives of phenomenology, biology, family history,
course of illness, comorbidity patterns, and treatment response have been
brought to bear on the question. Reviews based on research available by 1985
and 1991, respectively, arrived at differing conclusions: (1) that both disorders
shared common but non-specific sources, and (2) that the two disorders were
unrelated but co-occurred because of the high prevalence of each. Since the
time of these reviews, additional evidence has become available from a wider
range of biological investigations, better controlled comorbidity studies, studies
of the relationship of psychosocial stressors to the course of each disorder and
neuroimaging studies. In reviewing the more recent findings, we propose the
less parsimonious hypothesis that the disorders co-occur, both because they
share some common biological features and because the psychosocial sequella of
each can contribute to the development of the other. Depression and Anxiety
10:158–167, 1999. Published 1999 Wiley-Liss, Inc.†
Key words: comorbidity; borderline personality disorder; depression; affective
disorder
INTRODUCTION at the time from a number of research perspectives.
They evaluated comorbidity data, phenomenology,
T he high incidence of depressive symptoms among family prevalence, course of illness, biological factors,
patients with borderline personality disorder (BPD) has drug response, and psychodynamic/pathogenic mod-
stimulated interest in the interrelationship between bor- els. Four hypotheses were considered: (1) the affective
derline pathology and affective disorders. This has led to disorder, probably depression, is primary and leads to
the hypotheses that: (1) BPD is a variant of affective dis- the pathological character traits of BPD, (2) BPD can
order, (2) BPD predisposes to depression, or (3) both produce diagnosable affective disorders in some indi-
disorders share common etiologic features. Understand- viduals, (3) BPD and affective disorders are unrelated
ing the relationship between BPD and affective disorders and their coexistence in the same individual is the result
could help in formulating treatment strategies and in of the chance association of two prevalent disorders, and
predicting the course of illness. While a definitive model (4) BPD and affective disorders have overlapping non-
for the relationship between BPD and affective symp- specific sources. In the first review, Gunderson and
toms continues to be elusive, there has been a steady Elliott [1985] concluded that evidence for the first
evolution of our understanding of this issue, as evidence three hypotheses was not strong and they introduced
from a variety of perspectives has become available. A hypothesis 4 as most likely. By the time of the 1991
complicating factor is that a portion of the observed co-
occurance of BPD and depression may be artifactual,
since depressive states can have characteristics that re- Mood and Personality Disorders Program, The Mount Sinai
School of Medicine, New York, New York, and The Bronx
semble some of the DSM-IV criteria for BPD, such as
Veterans Administration Medical Center, Bronx, New York
the presence of suicidal threats or acts, intense episodic
dysphoria, or profound feelings of emptiness.
*Correspondence to: Harold W. Koenigsberg, M.D., Department
In two important studies of the relationship be- of Psychiatry, Bronx VA Medical Center (116A), 130 W. Kings-
tween borderline personality disorder (BPD) and de- bridge Rd., Bronx, NY 10468.
pression published in 1985 and 1991, Gunderson and
Elliott [1985], and Gunderson and Phillips [1991] ex- Received for publication 21 September 1999; Accepted 21 Sep-
amined this issue, synthesizing information available tember 1999
Published 1999 WILEY-LISS, INC. †This is a US Govern-
ment work and, as such, is in the public domain in the United
States of America.
www.cuwai.com Research Article: Depression and BPD 159
publication, comorbidity and family studies that better acutely depressed patients [Stuart et al., 1992]. In ad-
controlled for prior psychiatric history and comorbid dition, the concordance rate will be a function of the
diagnoses in the probands and that included other per- base rate of the disorders in the sample examined.
sonality disorders as comparison groups, were inter- Thus, for example, among psychiatric inpatients,
preted as refuting hypotheses 1 and 2. New biological where major depressive disorder (MDD) is highly
data refuted these hypotheses as well and strongly sup- prevalent, one would expect to find high rates of
ported hypothesis 3, while drug response patterns re- MDD among BPD patients. The most relevant esti-
futed hypothesis 1. On the basis of the research available mates of diagnostic overlap are therefore obtained by
in 1991, Gunderson and Phillips [1991] concluded that studying randomly selected community samples. Swartz
the hypothesis with strongest support was 3; i.e., that the et al. [1990] report a concurrent diagnosis of major de-
two disorders coexist but are otherwise unrelated. They pression in 40.7% of 24 subjects meeting their criteria
considered the family studies data that showed distinct for BPD in the community. Such studies must be viewed
familial transmission of BPD and affective illness, the cautiously, however, because of the methodological
qualitative difference in the depressive symptomatology, difficulties in accurately diagnosing personality disor-
and the differential pharmacotherapeutic response pat- der in epidemiologic catchment area studies [Weiss-
terns as particularly convincing. man, 1993]. The hypothesis that affective disorders
Since the publication of the Gunderson and Phillips contribute to the development of BPD is best exam-
[1991] review, additional work that addresses the rela- ined, not by looking at point prevalence rates of affec-
tionship between BPD and affective disorders has tive disorder in BPD, but at the lifetime prevalence of
been carried out. This includes additional biological, affective disorders among BPD patients. Zanarini et
neuroimaging, and family transmission studies, as well al. [1998] report an 82.8% lifetime prevalence of
as studies examining comorbidity in relation to the MDD and a 39% lifetime prevalence of dysthymia in
course of the disorders. their cohort of 379 borderline inpatients.
The early comorbidity studies examined concor-
COMORBIDITY RATES dance rates between BPD and various affective disor-
Most, but not all, studies of the association between ders without reporting comparison rates for other
BPD and affective disorders have shown high rates of personality disorders and other Axis I conditions. Such
overlap. Reports typically present either the incidence comparisons are essential to establish whether BPD is
of concurrent affective disorders among a group of specifically associated with affective disorders. Zana-
BPD patients (Table 1) or of BPD among cohorts of rini et al. [1998] find a 67.2% lifetime rate of MDD
patients with various affective disorders (Table 2). among 125 inpatients diagnosed with nonborderline
While these studies appear to show a strong associa- personality disorders. This is significantly lower than
tion between BPD and affective disorders, care must the 82.8% rate among inpatients diagnosed with BPD,
be taken in interpreting the findings. Personality dis- although still quite substantial. These authors also re-
order diagnoses may be falsely inflated if they are port high lifetime rates of nonaffective Axis I disorders
based upon information gathered by interviewing among their BPD probands: 88.4% for anxiety disor-
TABLE 1. Affective disorder frequencies among borderline personality disorder (BPD) patients
Comorbid diagnosis Study No. BPD subjects Type of sample Percent with diagnosis
Major depression Akiskal [1981] 100 Outpatient 6a
Carroll et al. [1981] 21 62
Pope et al. [1983] 33 Inpatient 39
Koenigsberg et al. [1985] 304 Mixedc 4
Swartz et al. [1990] 24 Community 41
Zanarini et al. [1998] 379 Inpatient 82b
Dysthymia Akiskal [1981] 100 Outpatient 14
Carroll et al. [1981] 21 5
Pope et al. [1983] 33 In patient 3
Koenigsberg et al. [1985] 304 Mixedc 1
Bipolar I Pope et al. [1983] 33 Inpatients 9
Koenigsberg et al. [1985] 304 Mixedc 0.3
Bipolar II Akiskal [1981] 100 Outpatient 17
Zanarini et al. [1998] 379 Inpatient 10b
Cyclothymia Akiskal [1981] 100 Outpatient 7
Koenigsberg et al. [1985] 304 Mixedc 0.3
a
Recurrent unipolar depression.
b
Lifetime rate.
c
Seventy-two percent outpatient and 28% inpatient.
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160 Koenigsberg et al.
TABLE 2. Borderline personality disorder frequencies among affective disorder patients
Affective disorder Study No. Type of sample Percent BPD
Major depression
Nonmelancholic Charney et al. [1981] 64 Inpatient 25
Melancholic Charney et al. [1981] 66 Inpatient 1.8
Koenigsberg et al. [1985] 315 Mixeda 4
Sanderson et al. [1992] 197 Outpatient 4
Early onset Fava et al. [1996] 137 Outpatient 23
Late onset Fava et al. [1996] 226 Outpatient 12
Dysthymia Koenigsberg et al. [1985] 68 Mixed 6
Sanderson et al. [1992] 63 Outpatient 8
Markowitz et al. [1992] 34 Outpatient 24
Bipolar I Koenigsberg et al. [1985] 171 Mixed 1
Ucok et al. [1998] 90 Outpatient 10
Cyclothymia Koenigsberg et al. [1985] 8 Mixed 13
a
Seventy-two percent outpatient and 28% inpatient.
ders, 55.9% for post-traumatic stress disorder (PTSD), mary). These studies have found nonsuppression rates
47.8% for panic disorder, and 53% for eating disorders. ranging from 9.5% to 62%. The earlier studies, which
In a sample equally divided between applicants for long- reported higher rates of nonsuppression, did not care-
term inpatient treatment of severe personality disorders fully exclude patients with coexisting MDD from their
and applicants for outpatient psychoanalysis, Oldham et samples [Yehuda et al., 1994]. The De la Fuente and
al. [1995] report odds ratios for the coexistence of BPD Mendlewicz [1996] study carefully excluded coexisting
and Axis I mood disorders, anxiety disorders, psychotic MDD in their BPD sample and also provided a com-
disorders, substance use disorders, and eating disorders parison MDD sample They report a 25% rate of
to be 1.8, 2.7, 4.9, 3.9, and 4.0, respectively. In this study, nonsuppression in the BPD group, compared to a
BPD co-occurred significantly with all axis I catego- 65% rate of nonsuppression in the MDD group.
ries except mood disorders. In addition, avoidant per- In addition to high rates of nonsupression of corti-
sonality disorder and dependent personality disorder sol by dexamethasone in MDD, these patients show
were the only personality disorders significantly asso- other signs of an overactive and less responsive HPA
ciated with axis I mood disorders (odds ratios: 3.2 and axis, such as higher baseline cortisol levels and a de-
2.6, respectively). In a sample of outpatients with MDD creased number of glucocorticoid receptors (GR)
and dysthymia, Sanderson et al. [1992] reports rates of compared to normals [Yehuda, 1998]. Since many
BPD of 4% and 8%, respectively. Among their MDD BPD patients have histories of childhood trauma
and dysthymic samples, however, six other personality [Herman et al., 1989], the alterations of HPA axis
disorders were at least as prevalent, with avoidant and function seen in PTSD may be relevant to the biology
dependent most prevalent. Taken together, these studies of BPD as well. PTSD patients have low baseline cor-
suggest that patients with BPD have high lifetime rates tisol levels, an increased number of GR receptors
of anxiety disorders as well as mood disorders, but that compared to normal controls or non-PTSD trauma
victims, and a hypersupression of cortisol in response
other personality disorders are also commonly associated
to low doses of dexamathasone compared to normal
with these Axis I conditions.
controls [Yehuda, 1998]. In a pilot study, our group
BIOLOGICAL STUDIES examined HPA axis function in 9 personality disorder
patients with histories of abuse, 14 healthy controls
Another approach to examining the relationship be-
with no histories of abuse, and 14 veterans with PTSD
tween BPD and affective disorders is to determine
[Grossman et al., 1997; Siever et al., 1998]. We found
whether they share common biological features. One
that the personality disorder patients had the lowest
of the best-studied biological features of MDD is the
over activity of the hypothalamic-pituitary-adrenal basal cortisol levels of the three groups and showed
(HPA) axis, which manifests in the nonsuppression of hypersupression of cortisol with low dose dexametha-
cortisol secretion in response to a dexamethasone sone. The number of lymphocyte GR receptors was,
challenge, the dexamethasone suppression test (DST). however, lower in the personality disorder patients
While the DST shows a high specificity (88% to 93%) than among the PTSD subjects. Thus, it appears that
for MDD in relation to normal controls, grief reac- in BPD, as in PTSD, there may be a hypersensitivity
tions and anxiety disorders, its sensitivity in MDD is of the HPA axis, reflected in low baseline cortisol lev-
only about 45% [Arana et al., 1985]. A large number els and hypersupression of cortisol to low dose dexam-
of studies of DST response in BPD have been carried ethasone, in contrast to MDD in which there is high
out (see De la Fuente and Mendelwicz [1996] for sum- basal cortisol and nonsupression, even to higher doses
www.cuwai.com Research Article: Depression and BPD 161
of dexamethasone. Increased lymphocyte GR number Postsynaptic alpha2 adrenergic activity can be mea-
may be a state variable seen in PTSD subjects, but not sured by the level of growth hormone (GH) secreted
in BPD or MDD subjects [Siever et al., 1998]. in response to the alpha 2 agonist, clonidine. The
A blunting of the thyroid stimulating hormone growth hormone response to clonidine has been re-
(TSH) response to thyrotropic releasing hormone ported to be blunted in males with acute or remitted
(TRH) infusion is found in approximately 30% of pa- major depression compared to healthy controls [Siever
tients with MDD [Duval et al., 1990]. Early studies of et al., 1992]. In a study of 92 personality disorder pa-
the TSH response to TRH in BPD subjects [Garbutt tients in our laboratory, comparing depressed and
et al., 1983; Nathan et al., 1986; Sternbach, 1983] nondepressed BPD patients, we found no significant
found evidence of blunting. When the co-occurrence difference in GH blunting between the groups
of MDD was carefully controlled for, however, the (Siever et al., unpublished data). It is possible that
rate of blunting in BPD was significantly lower than in in BPD patients, an opposing influence on alpha2
MDD [De la Fuentes and Mendlewicz, 1996]. The activity compensates for the blunting of the GH re-
standard TRH test has limited usefulness in establishing sponse seen in MDD. Coccaro et al. [1991] re-
a connection between BPD and affective disorders be- ported that, among personality-disordered patients
cause of its low sensitivity and specificity. A modification and normal controls, the magnitude of GH re-
of this test, which takes into account the chronobio- sponse to clonidine was proportional to levels of
logical rhythms of the hypothalamic-pituitary-thyroid self-rated irritability. This raises the possibility of
axis, the so-called delta-delta thyrotropin test, has a sen- increased alpha 2 adrenergic responsiveness in irri-
table BPD patients. Depression may be associated
sitivity of 89% and a specificity of 95% [Duval et al.,
with decreased adrenergic activity, while BPD may
1990]. This version of the TRH test would provide a
be associated with increased adrenergic activity.
more stringent means for identifying a common biologi-
Cholinergic systems control the onset of REM
cal response in BPD and affective disorders.
sleep. Decreased REM latency has been identified in
Increased platelet monoamine oxidase (MAO) activ-
patients with a history of MDD, both during episodes
ity has been identified as a trait marker in MDD
and during periods of euthymia. It appears to be a trait
[Gudeman et al., 1982]. Decreased platelet MAO ac-
marker for MDD. It has also been identified in first-
tivity has been described in association with personal-
degree relatives of MDD subjects. The majority of
ity characteristics such as sensation seeking [Demisch
sleep studies of BPD subjects [Akiskal, 1981; Mc-
et al., 1982; Donnelly et al., 1979; Fowler et al., 1980;
Namara et al., 1984; Reynolds et al., 1985; Akiskal et
von Knorring et al., 1984], impulsivity [Perris et al.,
al., 1985] have shown similar reductions in REM la-
1980; Schalling et al., 1987], and suicidality [Buchs-
tency to that reported in MDD patients. Unfortu-
baum et al., 1977; Gottfries et al., 1980], and percep-
nately, these findings do not address the question of
tual distortion in nonpsychotic subjects [Yehuda et al.,
whether BPD and MDD share common biological
1987]. An examination of platelet MAO activity in
characteristics because the BPD subjects in these stud-
BPD subjects could show whether they shared a bio-
ies either had concurrent MDD at the time of the
logical feature characteristic of MDD or of subjects
sleep study or had prior histories of MDD. A more
with borderline-like personality traits. Yehuda et al.
recent study by Battaglia et al. [1993] attempted to
[1989] showed that platelet MAO activity was signifi-
control for this complication by selecting 10 BPD pa-
cantly lower in a sample of 15 male nonpsychotic BPD
tients who had no current or prior histories of MDD,
patients compared with control subjects. There were
dysthymia, bipolar disorder, or cyclothymia. They re-
no significant differences when the BPD sample was
port REM latencies significantly shorter for BPD sub-
divided into those with and without concurrent MDD.
jects than nonpsychiatrically ill controls and in the
This finding was replicated by Reist et al. [1990].
range comparable to that of MDD subjects. There
In a series of studies, Southwick et al. [1990] and
was, however, a high rate of affective illness in the
Yehuda et al. [1994] compared the number of platelet
first-degree relatives of their subjects and the de-
alpha2-adrenergic receptor binding sites in a group of
creased REM latency appeared to be associated with
male and female inpatients with diagnoses of BPD-
the familial load for mood disorders. We can not,
only, BPD and MDD, MDD-only, and normal con-
therefore, exclude the possibility that the decreased
trols. Half of the BPD-only patients were medicated
with benzodiazepines at the time of the study and half REM latency was attributable to family history of af-
were medication-free. MDD-only patients had 60% fective disorder rather than to the proband’s personal-
more binding sites than controls, while BPD-MDD ity disorder.
patients had 30% fewer sites. Nonmedicated BPD The role of cholinergic systems in depression has
subjects also had fewer sites than normal controls, also been studied by examining emotional responses
while benzodiazepine-treated BPD patients did not to cholinomimetics. These agents have been shown to
differ from controls. This suggests a difference in no- transiently increase depression in depressed patients
radrenergic activity between BPD and MDD, but also [Janowski and Risch, 1987; Risch et al., 1983], and
raises the possibility that the difference might be ac- manic patients [Davis et al., 1978; Janowski et al.,
counted for by state anxiety. 1974], and to a lesser degree in normals [Risch et al.,
www.cuwai.com
162 Koenigsberg et al.
1983]. In a study of personality disorder patients, BPD region, particularly the medial frontal area, parts of
patients showed a greater depressive response to the the cingulate, the subgenual prefrontal cortex, and the
cholinomimetic, physostigmine, than normal controls dorsolateral prefrontal cortex [Buchsbaum et al., 1984;
or patients with other personality disorders [Steinberg Baxter et al., 1985, 1989; Cohen et al., 1989; Martinot
et al., 1997]. This depressive response to physostig- et al., 1990; Hurwitz et al., 1990; Biver et al., 1994;
mine was independent of current or past MDD, but Bench et al., 1992; Drevets et al., 1997]. In a carefully
did correlate with the degree of affective instability defined sample of familial pure depressive disorder
manifested by the patients. Thus, BPD and MDD pa- (FPDD) patients, Drevets et al. [1992] report in-
tients may share a heightened reactivity of cholinergic creased cerebral blood flow (CBF) in the left prefron-
systems. tal cortex and increased CBF in the left amygdala as
The serotonergic system has been implicated in de- well. Buchsbaum et al. [1997] demonstrated a normal-
pression and personality disorders. Decreased urinary ization of the decreased metabolic rate in the middle
and cerebrospinal fluid (CSF) levels of the serotoner- frontal gyrus, medial frontal lobe, cingulate gyrus, and
gic metabolite 5-hydroxy indolease acid (5-HIAA) thalamus following effective treatment of MDD with
have been identified in many studies of depression sertraline. In a PET study of 6 BPD patients, Goyer et
[Prange et al., 1974]. The so-called “permissive hy- al. [1994] found an decrease in metabolic activity in
pothesis” [Prange et al., 1974] posits that low levels of the anterior medial frontal cortex at a level 81 mm
serotonin reflect a trait that creates a vulnerability to above the canthomeatal line, and an increased activity
affective disorder. If central noradrenergic activity is in the anterior medial frontal cortex at a level 55 mm
low, depression will develop, and if the noradrenergic above the canthomeatal line. This pattern of activation
activity is elevated, mania will appear. While we now is consistent with that reported in the functional imag-
understand that more complex interactions between ing studies of depression. However, 3 of the 6 BPD
multiple neurotransmitter systems, receptor sites, sec- patients in the Goyer et al. [1994] study had histories
ond messenger systems, and gene products are likely of MDD, and this could account for the similarity.
to be involved in affective disorders [Duman et al., Recently, PET imaging has been combined with the
1997], the balance between serotonergic and noradr- pharmacological challenge approach to assess activity
energic activity appears to remain important. The of the serotonin system in regions of interest through-
responsivity of the serotonergic system in vivo can be out the brain. In patients with MDD, Mann et al.
examined by measuring the secretion of prolactin in [1996] demonstrated that the metabolic response to
response to the serotonin releasing agent and reuptake the serotonin releasing agent, d,l-fenfluramine, was
inhibitor, fenfluramine. Diminished prolactin re- blunted in the left prefrontal and temporoparietal cor-
sponses to fenfluramine have been observed in both tex, compared to healthy controls. Fenfluramine-in-
depression [Lopez-Ibor et al., 1988; Siever et al., duced activity in the right prefrontal cortex was
1984] and BPD [Coccaro et al., 1989]. The blunted greater in MDD than in controls. In a PET study
prolactin responses to fenfluramine, however, appear comparing six impulsive-aggressive personality disor-
to be more closely associated with impulsive aggres- dered patients, four of whom met criteria for BPD,
sion and suicidality in both populations than with di- with five healthy controls, the response to d,l-fen-
agnosis [New et al., 1997; Coccaro et al., 1997]. In a fluramine was reduced in the impulsive-aggressive pa-
sample of 73 personality disorder patients in our labo- tients compared to controls in the left lateral orbital
ratory (Siever et al., unpublished data), we found no frontal, adjacent ventral medial and bilateral cingulate
significant difference in blunted prolactin response cortices, right dorsolateral cortex, and right superior
between BPD patients with and without depression. parietal lobe [Siever et al., 1999]. While both studies
This may be because impulsive aggression was fairly had small sample sizes and may not be directly compa-
evenly distributed between the nondepressed BPD rable, taken together they raise the possibility of both
and depressed BPD patients. Thus, decreased seroto- similarities and differences in serotonergic activity
nin responsivity is found in both MDD and BPD, but between BPD and MDD. Both groups appeared to
it appears to be related most strongly to the levels of have decreased serotonin responsivity in the left
suicidality and impulsive aggression in the patients. prefrontal cortex. The BPD patients also had de-
creased responsivity in the cingulate, while the
NEUROIMAGING STUDIES MDD patients had decreased responsivity in the
The recent advent of PET scanning, SPECT, and temporoparietal region.
functional MRI have made it possible to identify pat-
terns of localized brain activity that characterize spe- TREATMENT RESPONSE
cific psychiatric disorders. This technology affords a Another approach to determining the degree of
powerful tool for ascertaining the relationship be- overlap between BPD and affective disorders is to
tween affective disorders and BPD. At present, a num- compare their responses to pharmacotherapy. A vari-
ber of functional imaging studies have been reported ety of classes of medication have been studied and data
in depressed subjects. The most consistent finding has are available about treatment response in individual
been a reduction in metabolic activity in the frontal symptom domains. While a number of studies have
www.cuwai.com Research Article: Depression and BPD 163
found that MAOI antidepressants reduce depresssion BPD, Links et al. [1995] found that the level of bor-
in BPD patients, as in MDD patients [Cowdry and derline psychopathology was a better predictor of de-
Gardner, 1988; Soloff et al., 1993; Parsons et al., pressive episodes during the follow-up period than
1989], the response to tricyclic antidepressants ap- was a prior history of unipolar depression. Perry et al.
pears to differ between the groups. Soloff et al. [1986] [1992] found that, in a sample of BPD patients, bor-
found that amitriptylene increased levels of hostile de- derline psychopathology predicted higher rates of ma-
pression in a subgroup of BPD patients. While SSRIs jor depressive episodes following life events, especially
appear to benefit borderline patients overall, a placebo those caused by the patient. This appeared to be be-
controlled study of fluoxetine by Salzman et al. [1995] cause borderline patients had more difficulty in coping
showed that their primary effect in BPD was in reduc- with the consequences of life events that they had
ing anger and not depression. On the other hand, wrought. A study by Fava et al. [1996] addressed the
neuroleptics, medications not noted to have antide- converse, the extent to which major depression might
pressant properties in the affective disorders, have contribute to the development of BPD. These authors
been shown to reduce depression in samples of BPD compared the frequencies of personality disorders in
patients [Soloff et al., 1989; Cowdry and Gardner, two groups of patients with MDD, those with onset
1988; Montgomery and Montgomery, 1982]. Mood before and after age 18. Patients in the early-onset
stabilizers such as carbamazepine, lithium, and val- MDD group had a signifianctly greater likelihood of
proate have been reported to be effective in BPD, but being diagnosed with BPD (67.9% vs. 49.1%). This
their primary effectiveness has been in reducing im- was also true for the diagnosis of narcissistic, antiso-
pulsivity or improving global function, rather than in cial, and avoidant personality disorder. These findings
reducing depression [Links et al., 1990; Stein et al., suggest that the relationship between prior MDD and
1995; Cowdry and Gardner, 1988]. Taken together, BPD is not specific, but that having MDD at an ear-
these findings suggest differences in the underlying lier age increases the likelihood of a personality disor-
biology of BPD and affective disorders. der. While this could be because depression occuring
during development could foster personality pathol-
COURSE ogy, it is also possible that early-onset depression is a
Examining the longitudinal course of patients ini- distinct disorder with greater direct effect on person-
tially diagnosed with BPD or affective disorders pro- ality functioning than late-onset depression.
vides another way to assess the relationship between
these disorders. In an early and influential study,
Akiskal [1981] followed 100 borderline patients for
DISCUSSION
periods ranging from 6 to 36 months. The observation In their 1991 examination of the relationship be-
that within 3 years 37% of these patients went on to tween BPD and depression, Gunderson and Phillips
develop episodes of affective disorder was cited by [1991] concluded that the two disorders frequently co-
Akiskal [1981] as evidence that BPD was a subaffective exist but are otherwise unrelated. Since then, a num-
form of affective illness. This sample contained 45 pa- ber of studies have been published addressing some of
tients who had comorbid affective disorder diagnoses the methodological limitations of the earlier work. In
at the intial evaluation. Among the 55 patients who particular, recent studies have more carefully ascer-
did not have concurrent affective disorder diagnoses at tained histories of prior depressive episodes, permit-
index evaluation, however, 20% went on to develop an ting an examination of lifetime comorbidity rates and
affective episode. A number of subsequent studies more clear-cut comparisons of biological variables be-
have followed BPD patients over longer time periods. tween “pure” BPD patients who had no history of
Pope et al. [1983] found that 23% of their cohort of prior depressive episodes and “pure” depressed pa-
inpatients with BPD who did not have an affective dis- tients without BPD. Recent studies have also exam-
order at index evaluation had an affective episode over ined BPD comorbidities with other Axis I disorders
their 4- to 7-year follow-up period. Over a 15-year and the comorbidities of other personality disorders
follow-up period, McGlashan [1987] found that only with depression as well.
6% of an inpatient sample of BPD subjects without Overall, the biological and treatment studies lend
coexisting unipolar depression at initial assessment de- support to the view that BPD and depression have
veloped unipolar depression. Overall, the follow-up both similarities and differences in their biology. Rela-
studies demonstrate that large numbers of BPD pa- tively few biological studies of BPD, however, have
tients do not go on to develop affective disorders over systematically controlled for histories of MDD, and
substantial time periods and that the BPD diagnosis is this may account for some of the discrepant findings
stable. This argues against the notion that BPD has a in the literature. Nevertheless, the studies to date sug-
strong etiological link to affective illness [Gunderson gest differences between BPD and MDD in HPA-axis
and Elliott, 1985]. activity, dexamethasone supression, platelet MAO ac-
More recent studies have pointed to an interactive tivity, platelet alpha2 receptor densities, and possibly
effect between BPD and depression. In their 7-year adrenergic activity. In depressed patients, basal corti-
follow-up of a cohort of inpatients diagnosed with sol levels are high and resistant to supression with
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164 Koenigsberg et al.
dexamethasone, while in BPD, as in PTSD, cortisol that offered in the review by Gunderson and Phillips
levels appear to be lower and more easily supressed. [1991]. First, as outlined above, shared biological fea-
Depressed patients may have reduced adrenergic ac- tures of the two disorders may account for part of the
tivity, while irritable BPD patients may have increased observed comorbidity. Another contributor may be
adrenergic activity. Reduced serotonergic activity ap- the psychosocial sequellae of the disorders, leading
pears to be common to both BPD and MDD, particu- each to predispose to the other. The impairments in
larly in those patients with suicidality or impulsive interpersonal skills, affective instability, impulsivity,
aggression. The PET studies suggest that both disor- and self-damaging behavior characteristic of BPD fre-
ders may share decreased serotonin responsivity in the quently lead to social and occupational failures, losses
left prefrontal cortex, but serotonergic activity may and humiliations, which are all significant psychosocial
also be reduced in the cingulate cortex in BPD pa- stressors. Stressful life events, especially dependent
tients. The REM latency data and the depressive re- life events, i.e., those resulting from the subject’s own
sponses to physostigmine suggest that cholinergic behavior, have been shown to be highly associated
dysregulation may be common to both disorders, per- with a subsequent depressive episode [Kendler et al.,
haps manifesting as affective instability when noradr- 1999]. Kendler et al. [1999] reported that, in a group
energic activity is elevated and as depression when of depressed women, 55% of all stressful life events
noradrenergic activity is diminished. were dependent. Because of the high level of impulsiv-
BPD is characterized by mood reactivity, while ma- ity and acting out among BPD patients, it is likely that
jor depression by a fixed dysphoric mood. Animal the rate of dependent life events in this population is
studies suggest that noradrenergic activity modulates even greater. Thus BPD could predispose to depres-
the degree of engagement with the environment and sive episodes by creating frequent stressful life events.
regulates aggressive reactions to perceived threats The findings of Perry et al. [1992] in a sample of bor-
[Lamprecht et al., 1972; Levine et al., 1990]. If norad- derline patients support this model.
renergic activity is high, there will be increased en- While BPD can thus contribute to subsequent de-
gagement with the social environment and greater pressions, the reverse is also likely. By generating sus-
mood reactivity, while if it is low, there may be a more tained anhedonia, emotional pain, and irritability,
fixed mood, more inward focus and less responsivity chronic depression could lead to enduring relationship
to external stimuli. Heightened cholinergic sensitivity patterns similar to those seen in borderline personality
may intensify dysphoric moods. Low serotonergic ac- disorder. The dysphoria and frustration of unremit-
tivity may contribute to the suicidality and impulsive ting depression are likely to lead to bouts of anger,
aggressiveness seen in both disorders. Thus, low sero- and tumultuous relationships. Since relationships with
tonergic activity, high cholinergic sensitivity, and low others can be a means of regulating one’s own affect
noradrenergic activity may be associated with depres- [Dunn, 1994], some depressed patients will rely upon
sion, whereas low serotonergic activity, high cholin- this mechanism of affect control, desperately needing
ergic sensitivity, and high noradrenergic activity may to keep others close, even by means of manipulative
be associated with BPD. Although this model begins behavior, threats of suicide, and frantic efforts to avoid
to account for commonalties and differences in the bi- separation. In this way, chronic depressive conditions
ology of BPD and depression, it is a fairly simplistic may give rise to some of the same interpersonal pat-
one. Other neurotransmitters, second messenger sys- terns that characterize BPD. Such “secondary” BPD
tems, and gene products are likely to play a role, and may be difficult to distinguish from “primary” BPD,
may account further for overlap and differences in the i.e., meeting the DSM-IV personality disorder re-
biology of MDD and BPD. quirement that “onset can be traced back at least to
Once prior history of depression is accounted for, adolescence or early adulthood.”
the rates for the development of subsequent depression The link between BPD and depression is not a spe-
in BPD patients are not much above those reported for cific one. BPD co-occurs with a number of Axis I dis-
the prevalence of depression in the population at large. orders, and depression can be comorbid with a variety
There are, however, high lifetime prevalences of de- of personality disorders. This is consistent with a psy-
pression and anxiety disorders among BPD patients chosocial model for the link between these disorders,
and patients with other personality disorders. The since any of the severe personality disorders may pre-
finding by Fava et al. [1996] that BPD is more com- dispose to stressful life events, and a number of Axis I
mon in patients with an earlier onset of major depres- symptoms such as anxiety and depression, especially
sion raises the possibility that a lengthy history of when chronic, can foster the maladaptive interper-
depression might predispose to BPD. Perry et al. sonal patterns which characterize BPD. As we are
[1992] found that in a sample of BPD patients, stressful learning more about the co-occurance of depression
life events that were a consequence of the patient’s be- and BPD, we are better appreciating how personality
haviors predicted depressive episodes. disorders can give rise to a life course punctuated by
In light of the more recent studies of the relation- multiple stressors, which are in turn precipitants for
ship between BPD and depression, we propose a dif- depressive disorders. Further work is called for to bet-
ferent and somewhat less parsimonious model than ter understand how dysfunctional personality patterns
www.cuwai.com Research Article: Depression and BPD 165
give rise to stressful life events and the relationship challenge correlate with behavioral irritability in psychiatric pa-
between these events and depressive episodes. In addi- tients and healthy volunteers. Psychiatry Res 39:129–139.
tion, we need to better understand the contributions Coccaro EF, Kavoussi RJ, Cooper TB , Hauger RL. 1997. Central
serotonin and aggression: inverse relationship with prolactin re-
of specific neurotransmitter systems to the affective
sponse to d-fenfluramine, but not with CSF 5-HIAA concentra-
symptoms in BPD and depression. Such work could tion in human subjects. Am J Psychiatry 154:1430–1435.
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