Original Research

Abuse and Neglect in Childhood:

Relationship to Personality
Disorder Diagnoses
By Linda M. Bierer, MD, Rachel Yehuda, PhD, James Schmeidler, PhD, Vivian Mitropoulou, MA,
Antonia S. New, MD, Jeremy M. Silverman, PhD, and Larry J. Siever, MD

ality disorder diagnoses or clusters and to lifetime history of suicide

FOCUS POINTS
• Childhood abuse and neglect have been described in a
substantial proportion of personality disorder subjects.
Sexual abuse in childhood has been noted particularly in
studies of borderline subjects.
• Studies reporting the highest prevalence of abuse have
generally been based on inpatient samples, reflecting a
bias toward severity of illness. Emotional abuse, highly
correlated with sexual and physical abuse, has been less
frequently assessed.
• The Childhood Trauma Questionnaire (CTQ) is a self-report
inventory that provides an index of five distinct dimen-
sions of trauma parameters (emotional, physical and sex-
ual abuse, and emotional and physical neglect).
• Results based on the CTQ administered in an outpatient
sample of personality disorder subjects indicated only
modest relationships between specific trauma dimensions
and personality disorder diagnoses. Sexual and physical
abuse were significant predictors of paranoid and antiso-
cial personality disorders; emotional abuse was a qualified
predictor of borderline personality disorder.
• Inferences with respect to the contribution of childhood
trauma to the development of personality disorders may
vary considerably depending on the gender distribution
and selection criteria of the sample.
ABSTRACT
Background: Childhood history of abuse and neglect has been
associated with personality disorders and has been observed in sub-
jects with lifetime histories of suicidality and self-injury. Most of
these findings have been generated from inpatient clinical samples.
Methods: This study evaluated self-rated indices of sustained
childhood abuse and neglect in an outpatient sample of well-char-
acterized personality disorder subjects (n=182) to determine the
relative associations of childhood trauma indices to specific person-
attempts or gestures. Subjects met criteria for ~2.5 Axis II diag-
noses and 24% reported past suicide attempts. The Childhood
Trauma Questionnaire was administered to assess five dimensions
of childhood trauma exposure (emotional, physical, and sexual
abuse, and emotional and physical neglect). Logistic regression
was employed to evaluate salient predictors among the trauma
measures for each cluster, personality disorder, and history of
attempted suicide and self-harm. All analyses controlled for gen-
der distribution.
Results: Seventy-eight percent of subjects met dichotomous
criteria for some form of childhood trauma; a majority reported
emotional abuse and neglect. The dichotomized criterion for global
trauma severity was predictive of cluster B, borderline, and anti-
social personality disorder diagnoses. Trauma scores were posi-
tively associated with cluster A, negatively with cluster C, but
were not significantly associated with cluster B diagnoses. Among
the specific diagnoses comprising cluster A, paranoid disorder
alone was predicted by sexual, physical, and emotional abuse.
Within cluster B, only antisocial personality disorder showed sig-
nificant associations with trauma scores, with specific prediction
by sexual and physical abuse. For borderline personality disorder,
there were gender interactions for individual predictors, with emo-
tional abuse being the only significant trauma predictor, and only
in men. History of suicide gestures was associated with emotional
abuse in the entire sample and in women only; self-mutilatory
behavior was associated with emotional abuse in men.
Conclusion: These results suggest that childhood emotional
abuse and neglect are broadly represented among personality dis-
orders , and associated with indices of clinical severity among
patients with borderline personality disorder. Childhood sexual and
physical abuse are highlighted as predictors of both paranoid and
antisocial personality disorders. These results help qualify prior
observations of the association of childhood sexual abuse with bor-
derline personality disorder.
C N S Spectr 2003;8(10):737-740,749-754

Dr. Bierer is clinical associate professor in the Department of Psychiatry, Dr. Yehuda is professor in the Department of Psychiatry, Dr. Schmeidler is assis-
tant clinical professor in the Departments of Psychiatry and Biomathematical Sciences, Ms. Mitropoulou is administrative director at the General Clinical
Research Center, Dr. New is assistant professor in the Department of Psychiatry, Dr. Silverman is associate professor in the Department of Psychiatry,
Dr. Siever is professor in the Department of Psychiatry, all at Mount Sinai School of Medicine in New York City.
Disclosure: This work was supported by funding from the National Institute of Mental Health grant #ROl-MH5606 to Dr. Siever, the Department of
Veterans Affairs (MERIT awards to Dr. Siever and to Dr. Yehuda, the VISN3 MIRECC award), and the National Institute of Health-Center for Research
Resources, awarded to Mount Sinai School of Medicine). Paper submitted on June 23, 2003, and accepted on August 5, 2003.
Please direct all correspondence to: Linda M. Bierer, MD, Bronx Veterans Affairs Medical Center ( O O M H ; 116-A), 130 West Kingsbridge Rd, Bronx,
NY 10468; Tel: 718-584-9000, Fax: 718-741-4775; E-mail: lmda.bierer@med.va.gov.
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737 CNS Spectrums - October 2003
 Original Research
INTRODUCTION
Models of personality disorder development have posited a
central contribution of childhood trauma exposure.12 Initial
observations of the frequent occurrence of childhood sexual
abuse among women with borderline personality disorder3
(BPD) have been replicated numerous times4 and extended
to include observations of childhood traumatic antecedents
associated with several personality disorders or clusters.2
Longitudinal studies have suggested that abuse and neglect in
childhood generally confer an increased risk for the develop-
ment of personality disorders. 2 Specific traumatic
antecedents, however, have been variably and less consis-
tently associated with individual personality disorders or
behavioral dimensions.5 Results based on large community-
based samples6'8 have often differed from those based on
selected clinical samples.89 Further, discrepant results may
reflect differences in the source,410 clinical severity,1112 and
diagnoses"14 of the comparison groups employed.
History of suicide attempts has also been linked to child-
hood history of sexual and physical abuse,12131516 and has
become a more recent focus of study. Not only do these behav-
iors contribute directly to the diagnosis of BPD, they are associ-
ated with psychiatric comorbidities that are often present in
personality disorder subjects.17'20 Unfortunately, studies in
which childhood abuse has been detected among subjects with
histories of suicide attempts have not typically also assessed per-
sonality disorder diagnoses.10'21'23 The interrelationships among
these behavioral outcomes, personality disorder diagnosis, and
antecedent trauma have not been fully explored.
One explanation for the preponderance of studies in
which sexual and physical abuse, in contrast to other forms
of childhood maltreatment, are reported in association with
personality disorder diagnoses is that these behaviors are
readily identified and lend themselves to quantification.
Appreciation of the contributions of childhood emotional
and verbal abuse, and of emotional, rather than physical
neglect, has increased, however, with the development of
appropriate rating scales for their assessment.2425 It has been
suggested that even highly disturbing experiences can be
assimilated adaptively by children raised in the setting of a
nurturing and responsive home,26'28 drawing attention to the
possibility that repeated and prolonged abuse,29 or abuse that
occurs in an atmosphere of neglect,9 may be critical in deter-
mining associations with character pathology or diagnosis.
Thus, the co-occurrence of neglect has increasingly been
conceived as an important moderator of morbidity associated
with physical and sexual abuse.
This study utilized the Childhood Trauma Questionnaire
(CTQ),10 a self-report measure assessing emotional abuse and
neglect, physical abuse and neglect, and sexual abuse in
childhood in a sample of well-characterized personality disor-
der subjects. Trauma scores were evaluated for subjects meet-
ing diagnoses within each of three clusters, for individual
personality disorders, and for history of attempted suicide and
self-mutilatory behaviors. Our aim was to determine the spe-
cific relationships of CTQ measures of abuse and neglect to
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personality disorder diagnoses, to the expression of suicidal
and self-injurious behavior, and to evaluate the possibility
that there might be gender differences in these relationships.
METHODS
Subjects
Subjects were either referred for research participation
to the Mood and Personality Disorders program from the
outpatient psychiatric clinics at the Mount Sinai School
of Medicine or the Bronx Veterans Affairs Medical Center
or self-referred in response to advertisements and press
releases. Procedures for this study were approved by the
Mount Sinai Institutional Review Board and all subjects
provided written informed consent. Each subject under-
went a diagnostic evaluation by a trained Master's level
psychologist using the Schedule for Affective Disorders
and Schizophrenia31 and the Structured Interview for the
Diagnostic and Statistical Manual of Mental Disorders, Third
Edition, Revised Personality Disorders.32 The latter included
an interview with an informant close to the subject. The
interrater reliability K for each of the personality disorder
diagnoses were as follows: schizoid: 0.84; dependent: 0.84;
narcissistic: 0.82; BPD: 0.81; avoidant: 0.79; schizotypal:
0.73; passive—aggressive: 0.72; paranoid: 0.68; obsessive-
compulsive: 0.67; histrionic: 0.59; and antisocial: 0.56. All
sources of available information were reviewed in a con-
sensus conference chaired by JMS.33 Subjects were assigned
all diagnoses for which they fulfilled criteria, and to cluster
A, B, or C if they met criteria for at least one personality
disorder within that cluster.
Only those subjects evaluated subsequent to 1996 were
systematically questioned with respect to posttraumatic
stress disorder symptoms (n=130). Patients meeting crite-
ria for primary psychotic disorders (including schizophre-
nia or bipolar I disorder), lifetime history of substance
dependence or intravenous drug use, alcohol or substance
abuse disorder within the previous 6 months, or significant
medical or neurologic disorders were excluded from the
current sample because, in such subjects, the assessment of
personality disorders cannot be determined with sufficient
reliability. Patients with mood and/or anxiety disorders
and patients with a lifetime history of alcohol or substance
abuse disorders were included.
Childhood Trauma Questionnaire
Each participant completed the short form of the CTQ,34
a self-report instrument that provides a subjective assessment
of the participant's childhood environment. Unlike scales
that account for individual occurrences of events likely to be
experienced as psychological or physical traumas, this instru-
ment evaluates the nature of the interpersonal environment
in which an individual grew up and, while incorporating ref-
erences to traumatic events, captures a subject's recollections
of the perceived likelihood of disturbing or traumatic occur-
rences. Items begin with phrases such as "When I was grow-
ing up..." and are scored on a five-point Likert-type scale
738 CNS Spectrums - October 2003
 Original Research

indicating frequency of occurrence in childhood. Five distribution), logarithmic transformations were applied to
dimensions of childhood trauma are measured: emotional the CTQ subscales when used in logistic regression analyses,
abuse, physical abuse, sexual abuse, emotional neglect, and described below. Trauma scores were converted to dichoto-
physical neglect. The content validity of these dimensions mous ratings for each subscale and for the total score accord-
has been confirmed by factor analysis; the scale has been ing to cut-off scores developed by Bernstein and colleagues'5
shown to provide stable scores over time35 and to be consis- to indicate the presence or absence of exposure. These rat-
tent with information obtained from corroborative sources ings were used to compare the proportions of subjects report-
close to the subject.3637 ing trauma exposure with and without specific diagnoses and
cluster assignments.
Measures of Suicidality and Self-Mutilation To predict cluster assignment, or personality disorder diag-
Suicidal behavior was rated according to responses to four nosis within each cluster, on the basis of logarithmically
questions posed as part of the Schedule for Affective transformed childhood trauma variables, stepwise logistic
Disorders and Schizophrenia interview: reported history of regression procedures were performed. Gender was entered as
suicide attempts and/or "gestures," number of suicidal the first predictor so that the effect of all subsequent predic-
attempts, suicidal intent of the most serious gesture, and tors could be evaluated controlling for differences in gender
actual medical threat posed by the most serious gesture or distribution. Scores for the five CTQ subscales were entered
attempt. If subjects responded affirmatively to the question collectively in the next step; parallel analyses were per-
"Have you ever tried to commit suicide?," they were given a formed in which each trauma score was entered individually
positive rating for suicide attempt history, regardless of med- to identify the strongest significant predictors among the five
ical lethality or likelihood of success. Self-mutilation was trauma dimensions. The interactions of gender with the five
rated positively, based on questions posed during the CTQ subscales were entered in a third step, and were simi-
Structured Interview for the Diagnostic and Statistical Manual larly examined individually to identify gender interactions
of Mental Disorders, Third Edition, Revised Personality with specific CTQ measures. Suicide attempt and self-muti-
Disorders,38 for subjects who reported having caused tissue lation history were subjected to the same logistic regression
damage, whether this occurred as part of a suicide gesture or procedures. In view of the presence of several gender interac-
attempt, or as a means of modulating dysphoric affective tions, logistic regression analyses were also performed for
states without conscious suicidal intent. Examples of rated men and women separately.
behaviors included puncture wounds and biting, scratching, Since there were about twice as many men as women in
or slicing the skin to the point of causing pain and bleeding. this sample, tests of significance are not useful descriptive
statistics for comparing the strengths of associations for men
Statistical Analyses and women, respectively, of childhood trauma scores with
The responses of six subjects to the C T Q were deemed cluster or personality disorder diagnoses. For descriptive pur-
unreliable according to ratings (ie, scores >1) on an internal poses, Pearson correlations were calculated between contin-
scale designed to identify subjects with tendencies to mini- uous measures of trauma and dichotomous diagnoses
mize severity ratings. Therefore, results are reported only for (ie, point-biserial correlations) to provide measures of associ-
the personality disorder subjects (n=182) with valid CTQ ation that do not depend directly on sample size. Their tests
scores. Initial analyses were performed to check for age and of significance are identical to those for Student's t-tests
gender characteristics as possible covariates. Gender differ- comparing the means of CTQ subscales for subjects with and
ences in the frequencies of Axis I and II diagnoses were without a particular personality diagnosis, and for discrimi-
assessed using Pearson %2, with continuity correction if any nant analyses in which single CTQ subscale scores are used
expected frequency was <5. Numbers of Axis I and II diag- as diagnostic discriminators. Partial correlations, controlling
noses were compared for male and female subjects using for gender, are presented for the entire sample, and simple
analysis of variance (age was not controlled for in either correlations for men and women separately. Untransformed
analysis as it was not associated with numbers of diagnoses). C T Q measures were used for the correlational analyses so
Logistic regression, controlling for gender, was used to test that the descriptive statistics would directly relate to the
the significance of associations among measures of suicidal- means of CTQ scores.
ity, self-mutilation and Axis I and Axis II diagnoses. Since the associations of each trauma dimension with
The interrelationships among the CTQ subscales, CTQ specific personality disorder diagnoses were of interest, signif-
total score, and age were assessed by partial correlation, con- icance levels were not adjusted for multiple comparisons.
trolling for gender. Correlations were calculated separately This problem is mitigated by the use of analyses that include
for males and females. Since age was not significantly corre- all of the trauma subscales, or predict cluster assignments
lated with any of the CTQ measures, it was not controlled that provide summary variables for groups of diagnoses. In
for in analyses involving the CTQ. Since the CTQ items for addition to its interpretation as the multivariate prediction
sexual abuse (kurtosis=3.5), and to a lesser extent physical of a diagnosis by five CTQ scales, a logistic regression analy-
neglect (kurtosis=2.1), were quite kurtotic (ie, demonstrated sis may also be interpreted as an overall test of significance
more extreme values than would be expected in a normal for the individual predictors.

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 Original Research
FINDINGS
Sample Characteristics
Diagnoses
Personality disorder subjects (118 men, 64 women) were
studied with mean±SD age of 37.8±8.4 years. BPD was the
most common diagnosis (39%), followed by paranoid (31%),
avoidant (30%), and schizotypal (26%) (Table 1).
Approximately 50% of the sample received cluster A and B
diagnoses, whereas a somewhat higher proportion received
diagnoses in cluster C (63.2%), with 51.1% assigned to only
one cluster, 32.4% to two clusters, and 16.5% to three.
A pertinent example of the co-occurrence of diagnoses
across clusters was the significant association, controlling for
gender, of paranoid personality disorder (cluster A) with
both BPD (X2=6.O2, d/=l, P=.O14) and antisocial (%2=6.84,
4f=l, P=.OO9) personality disorders (cluster B). The most
common comorbid lifetime Axis I diagnosis was major
depressive disorder (78%) which was associated with BPD
(X2=9.96, df=l, P=.002), controlling for gender, but with no
other personality diagnosis or cluster.
The prevalence of Axis 1 and II disorders for males and
females are compared in Table 1. In this sample, similar pro-
portions of men and women were diagnosed with lifetime
history of major depression; but history of suicide attempts
and self-mutilation were substantially more frequent in
women. Women were significantly more likely to be diag-
nosed as borderline, dependent, and histrionic, whereas men
were more often schizoid and antisocial, consistent with gen-
erally reported gender distributions for these diagnoses. Men
and women were diagnosed with similar numbers of Axis II
disorders at the time of evaluation (2.45±0.64 for women,
2.47± 1.59 for men), and were diagnosed with disorders rep-
resented across similar numbers of clusters (1.70+0.77 for
women, 1.63±0.74 for men).
Trauma Ratings
All of the CTQ subscales were substantially intercorre-
lated. The partial correlations, controlling for gender, ranged
from 0.59-0.28 (all, d/=179, P<.0005), with the single
exception of sexual abuse and emotional neglect (r=.2O,
ctf= 179, P=.OO6). The strongest correlations among the
CTQ measures were for emotional abuse with emotional
neglect (r=.59) and physical abuse (r=.58), respectively.
Similar results were apparent for CTQ subscale intercorrela-
tions among males and females examined separately, but
were generally somewhat higher among the female than
male subjects. The magnitudes of these associations suggest
that specific forms of abuse tend not to occur in isolation,
and provide the rationale for performing logistic regression
analyses using five predictors collectively.
Based on normative data for the CTQ subscales,35 only a
subset of subjects met threshold criteria for exposure to spe-
cific dimensions of abuse and neglect. These were distributed
as follows: emotional abuse (59.9%), physical abuse (41-2%),
sexual abuse (32.4%), emotional neglect (57.1%), and phys-
ical neglect (27.5%), with 77.5% of subjects meeting criteria
for trauma exposure in at least one dimension. On the basis
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of the total score, 46.7% met severity criteria for trauma
exposure. By these criteria, a greater proportion of women
than men reported exposure to emotional abuse (%2=9.38
df=l, P=.OO2), emotional neglect (x2=6.99, df=l, P=.OO8),
and sexual abuse (%2=4.30, df=\, P=.038) A majority of per-
sonality disorder subjects, female subjects, in particular,
showed evidence of childhood emotional abuse and neglect
(Figure 1). Female subjects reported higher scores than males
for C T Q subscales of sexual abuse (F= 12.22; <i/=l,178;
P=.001) and emotional abuse (F=6.75; d/=l,178; P=.010).
In consideration of these differences, gender was controlled
for in analyses involving CTQ ratings.
History of Attempted Suicide and Self-Harm
History of suicide gestures and/or attempts was positive in
23.8% subjects for whom data was available on this measure,
and history of self-mutilatory acts was positive in 22.1% of
subjects. Self-mutilation history was fairly evenly distributed
among subjects with (n=22) and without (n=18) history of
suicide attempts. Controlling for gender, suicidality was sig-
nificantly associated with major depressive disorder
(%2=5.OO, df=\, P=.025), whereas self-mutilation was not
(X2=2.69, df=l, P=.101). Suicide gestures (r=.162, d/=178,
P=.O3O), but more strongly, self-mutilation (r=.305, d/= 179,
P<.0005) were associated with BPD, controlling for gender.
Thirty-one subjects reported only one prior suicide attempt
or gesture, while 12 subjects reported two or more such inci-
dents. There was a tendency for subjects with histories of
self-mutilation to be among those with multiple, rather than
single, suicide gestures (%2=3.79 df=l, P=.052).
Relationships of Trauma Ratings to Diagnoses,
Attempted Suicide, and Self-Harm
Global Ratings Based on Threshold Criteria
There were no relationships between meeting threshold
criteria for one or more traumatic exposures and any cluster
characterization, diagnosis, suicide history, or self-mutilation.
Using the somewhat more refined measure of meeting thresh-
old criteria for trauma exposure based on the total CTQ score
("trauma experience"), a positive association, controlling for
gender, was found for trauma experience with cluster B assign-
ment (%2=5.25, df=l, P=.022) which reflected significant pre-
diction of borderline (x2=8.25 df=l, P=.OO4) and antisocial
(%2=5.25, df=l, P=.O22) diagnoses, but not for suicide or self-
harm variables. These associations, however, are based on a
global index of trauma experience that neither distinguishes
between moderate and severe exposure, nor illuminates the
relevance of specific trauma dimensions. The use of the five
CTQ subscales scores provide more sensitive indices of the
extent of exposure of various types.
Descriptive Statistics for Mean Childhood Trauma
Questionnaire Scores
Figure 2 displays the difference in mean CTQ ratings for
subjects with and without diagnoses in clusters A, B, and C,
respectively. Tests of significance for subjects with and with-
out each cluster assignment, controlling for gender, are
continued on page 749 ^
740 CNS Spectrums - October 2003
 A different path to success
in your continuing treatment
of schizophrenia

DISCOVER PROVEN EFFICACY,

TOLERABillTY, AND SAFETY FOR THE ROAD AHEAD

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 road not traveled before

Unique Pharmacology Sets

Abilify Apart1

Abilify is a partial agonist that uniquely

modulates dopamine activity.12
- Functional antagonist activity at D2 receptors in a
/?j/pmlopaminergic environment 1

- Functional agonist activity at D2 receptors in a

/ i c environment 1

Serotonin antagonist activity at 5-HT2A receptors and

partial agonist activity at 5 - H T \ A receptors

Abilify has moderate affinity for alpha^adrenergic and

histamine (H^) receptors

Abilify has no appreciable affinity for cholinergic

muscarinic receptors

The mechanism of action of Abilify, as with other drugs having efficacy

in schizophrenia, is unknown.
Abilify is indicated for the treatment of schizophrenia.
Please see Brief Summary of Prescribing Information on last page of this insert.

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 The Confidence of Proven Efficacy
Significant improvement as early as Week I3
t

PANSS Total Score

2

mtm Ability 15 mg
= * - Ability 20 mg
Ability 30 mg
Placebo

-15
Baseline 3
Study week

Ability 15 mg (n=202), 20 mg (n=195), 30 mg (n=196), and placebo (n=312). Analysis included data from all fixed-dose trials.
•Last observation carried forward.
|P<0.05 vs placebo.
tP<0.01 vs placebo.

• In efficacy studies, 88% of responders did not

experience sedation3

In multiple, placebo-controlled trials, somnolence was reported

in 11% of patients on Abilify compared to 8% of patients on
placebo; somnolence led to discontinuation in 0.1% of
patients on Abilify in these clinical trials. In clinical trials, the
only adverse event to have a possible dose-response relationship
was somnolence (placebo, 7.7%; 15 mg, 8.7%; 20 mg, 7.5%;
ABILIFY
and 30 mg, 15.3%).
(aripiprazole)
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 course with few detours

Tolerability and Safety

for the Road Ahead

Weight3 - Mean weight change of 1 kg over 1 year

Sedation* - 1 1 % vs placebo 8%

EPS* - 6% vs placebo 6%

Hyperprolactinemia3 - 1 . 8 % vs placebo 6.9%

QTC interval - No significant difference vs placebo

* Patient-reported adverse events in 4- and 6-week placebo-controlled trials.

f i n patients with prolactin levels less than or equal to the upper limit of normal at baseline.

In a 52-week study, the percentage of patients with >7% increase in body

weight was 30% for those with BMI (Body Mass Index [kg/m2]) <23, 19% for
those with BMI 23 to 27, and 8% for those with BMI >27.
In short-term trials, there was a slight difference in mean weight gain between
Abilify and placebo patients (+0.7 kg vs -0.05 kg respectively), and also a
difference in the proportion of patients meeting a weight gain criterion of >7%
of body weight for Abilify (8%) compared to placebo (3%).

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 Effect of Abilify on weight, long term

Change in Weight Over 1 year1

BMI <23 BMI 23-27 BMI >27

(low) (normal) (high)

A prospective 52-week, double-blind trial. For Abilify, BMI <23 (n=314); BMI 23 to 27 (n=265); and BMI >27 (n=260).
The percentage of patients with >7% increase in body weight was 30% for those with BMI <23, 19% for those with BMI 23 to 27,
and 8% for those with BMI >27.
f Last observation carried forward.

~ Because patients' overall health is important

Abilify is comparable to placebo on§3:

• Glucose
• HDL
• LDL
• Triglycerides

Data from a 6-week, placebo-controlled, clinical trial.

§As measured by routine serum chemistry analysis.

Please see Brief Summary of Prescribing

ABILIFY
Information on last page of this insert.
(aripiprazole)

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 clear path for the journey ahead

Few patients discontinue due to adverse events

with Abilify

40-i

s • Abilify

J« 30- • Placebo
adver se eve
>iscont inuing

20-

7%* 9%
as
10-

0- •_
Pooled data from five 4 - t o 6-week, placebo-controlled clinical trials.
There is no statistical difference in the incidence of discontinuation due to adverse events, and the types of adverse events
that led to discontinuation were similar between placebo-treated patients and patients treated with Abilify.

Treatment-emergent adverse events reported at an incidence >10% and

greater than placebo include headache, anxiety, insomnia, nausea, vomiting,
lightheadedness, somnolence, akathisia, and constipation.
As with all antipsychotic medications, a rare condition referred to as neuroleptic
malignant syndrome (NMS) has been reported. As with all antipsychotic medi-
cations, prescribing should be consistent with the need to minimize the risk of
tardive dyskinesia (TD).
Abilify may be associated with orthostatic hypotension and should be used with
caution in patients with known cardiovascular disease, cerebrovascular disease,
or conditions which would predispose them to hypotension.
As with other antipsychotic drugs, Abilify should be used with caution in
patients with a history of seizures or with conditions that lower the seizure
threshold. Seizures occurred in 0.1% of Abilify-treated patients in placebo-
controlled trials.

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 Abilify Makes Dosing Easy
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Information on last page of this insert.

References:
1. Burris KD, Molski TF, XU C, et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human
dopamine D2 receptors. The Journal ofPharmacology and Experimental Therapeutics. 2002;302:381-389.
2. Kikuchi T, Tottori K, Owahodo Y, et al. 7-{4-[4-(2,3-dichlorophenyl)-l-piperazinyl]butyloxy}-3,4-dihydro-2
(1 H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor
agonist activity and postsynaptic D2 receptor antagonistic activity. The Journal of Pharmacology and Experimental
Therapeutics. 1995;274:329-336.
3. Data onfile.Otsuka America Pharmaceutical, Inc., Rockville, Md.
Marketed by Otsuka America Pharmaceutical, Inc., Rockville, MD 20850 USA and Bristol-Myers Squibb Co., Princeton, NJ 08543 USA.
Manufactured by Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan.
Distributed by Bristol-Myers Squibb Co., Princeton, N] 08543.
U.S. Patent Nos. 4,734,416 and 5,006,528.

T|N|=7 Bristol-Myers Squibb Company Otsuka America Pharmaceutical, Inc.

ABILIFY
©2003, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan
D6-K0047 A4232/05-03 June 2003 Printed in USA © Printed on recycled paper.
(aripiprazole)

Downloaded from https:/www.cambridge.org/core. New York University, on 03 Feb 2017 at 16:21:16, subject to the Cambridge Core terms of use, available at
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Rx only
1 death were pneumonia, heart failure, and shock). The fourth patient (age 78
ABILIFY FTM
(aripiprazole) Tablets
Brief Summary of Prescribing Information. For complete prescribing information pilot, open-label, ascending-dose cohort study (n=30) in elderly patients with
please consult official package circular.
INDICATIONS AND USAGE
ABILIFY (aripiprazole) is indicated for the treatment of schizophrenia. The
efficacy of ABILIFY in the treatment of schizophrenia was established in short-
term (4- and 6-week) controlled trials of schizophrenic inpatients (see CLINICAL
PHARMACOLOGY: Clinical Studies). The long-term efficacy of aripiprazole in
the treatment of schizophrenia has not been established. The physician who
elects to use ABILIFY for extended periods should periodically re-evaluate the
long-term usefulness of the drug for the individual patient.
CONTRAINDICATIONS
ABILIFY is contraindicated in patients with a known hypersensitivity to the product. Information for Patients: Physicians are advised to consult full prescribing
WARNINGS
Neurolaptic Malignant Syndrome (NMS): A potentially fatal symptom complex
sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been
reported in association with administration of antipsychotic drugs, including
aripiprazole. Two possible cases of NMS occurred during aripiprazole treatment
in the premarketing worldwide clinical database. Clinical manifestations of NMS
are hyperpyrexia, muscle rigidity, altered mental status, and evidence of auto-
nomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2E1
cardiac dysrhythmia). Additional signs may include elevated creatine phospho-
kinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The diagnostic
evaluation of patients with this syndrome is complicated. In arriving at a diag-
nosis, it is important to exclude cases where the clinical presentation includes
both serious medical illness (e.g., pneumonia, systemic infection, etc) and
untreated or inadequately treated extrapyramidal signs and symptoms (EPS).
Other important considerations in the differential diagnosis include central anti-
cholinergic toxicity, heat stroke, drug fever, and primary central nervous system
pathology. The management of NMS should include: 1) immediate discontinua-
tion of antipsychotic drugs and other drugs not essential to concurrent therapy;
2) intensive symptomatic treatment and medical monitoring; and 3) treatment of
any concomitant serious medical problems for which specific treatments are
available, There is no general agreement about specific pharmacological treat-
ment regimens for uncomplicated NMS. If a patient requires antipsychotic drug
treatment after recovery from NMS, the potential reintroduction of drug therapy
should be carefully considered. The patient should be carefully monitored, since
recurrences of NMS have been reported. Tardive Dyskinesia: A syndrome of
potentially irreversible, involuntary, dyskinetic movements may develop in
patients treated with antipsychotic drugs. Although the prevalence of the syn-
drome appears to be highest among the elderly, especially elderly women, it is
impossible to rely upon prevalence estimates to predict, at the inception of
antipsychotic treatment, which patients are likely to develop the syndrome.
Whether antipsychotic drug products differ in their potential to cause tardive
dyskinesia is unknown. The risk of developing tardive dyskinesia and the likeli-
hood that it will become irreversible are believed to increase as the duration of
treatment and the total cumulative dose of antipsychotic drugs administered to
the patient increase. However, the syndrome can develop, although much less
commonly, after relatively brief treatment periods at low doses. There is no
known treatment for established cases of tardive dyskinesia, although the syn-
drome may remit, partially or completely, if antipsychotic treatment is with-
drawn. Antipsychotic treatment, itself, however, may suppress (or partially sup-
press) the signs and symptoms of the syndrome and, thereby, may possibly
mask the underlying process. The effect that symptomatic suppression has upon
the long-term course of the syndrome is unknown. Given these considerations,
ABILIFY should be prescribed in a manner that is most likely to minimize the
occurrence of tardive dyskinesia. Chronic antipsychotic treatment should gener-
ally be reserved for patients who suffer from a chronic illness that (1) is known
to respond to antipsychotic drugs, and (2) for whom alternative, equally effec-
tive, but potentially less harmful treatments are not available or appropriate. In
patients who do require chronic treatment, the smallest dose and the shortest
duration of treatment producing a satisfactory clinical response should be
sought. The need for continued treatment should be reassessed periodically. If
signs and symptoms of tardive dyskinesia appear in a patient on ABILIFY, drug
discontinuation should be considered. However, some patients may require
treatment with ABILIFY despite the presence of the syndrome.
PRECAUTIONS
General: Orthostatic Hypotension: Aripiprazole may be associated with orthosta- of Fertility: (Please see Full Prescribing Information).
tic hypotension, perhaps due to its ui -adrenergic receptor antagonism.The inci-
dence of orthostatic hypotension associated events from five short-term, place-
bo-controlled trials in schizophrenia (n=926) on ABILIFY (aripiprazole) included:
orthostatic hypotension (placebo 1%, aripiprazole 1.9%); orthostatic lighthead-
edness (placebo 1%, aripiprazole 0.9%), and syncope (placebo 1%, aripiprazole
0.6%). The incidence of a significant orthostatic change in blood pressure
(defined as a decrease of at least 30 mmHg in systolic blood pressure when
changing from a supine to standing position) for aripiprazole was not statistical-
ly different from placebo (14% among aripiprazole-treated patients and 12%
among placebo-treated patients). Aripiprazole should be used with caution in
patients with known cardiovascular disease (history of myocardial infarction or
ischemic heart disease, heart failure or conduction abnormalities), cerebrovas-
cuiar disease, or conditions which would predispose patients to hypotension
(dehydration, hypovolemia, and treatment with antihypertensive medications).
Seizure: Seizures occurred in 0.1% (1/926) of aripiprazole-treated patients in
short-term, placebo-controlled trials. As with other antipsychotic drugs, aripipra-
zole should be used cautiously in patients with a history of seizures or with con-
ditions that lower the seizure threshold, e.g., Alzheimer's dementia. Conditions
that lower the seizure threshold may be more prevalent in a population of
65 years or older. Potential for Cognitive and Motor Impairment: In short-term, (>65 years) compared to younger adult subjects (18 to 64 years), but there was
placebo-controlled trials, somnolence was reported in 11% of patients on
ABILIFY compared to 8% of patients on placebo; somnolence led to discontinu-
ation in 0.1% (1/926) of patients on ABILIFY in short-term, placebo-controlled
trials. Despite the relatively modest increased incidence of somnolence com-
pared to placebo, ABILIFY, like other antipsychotics, may have the potential to
impair judgment, thinking, or motor skills. Patients should be cautioned about
operating hazardous machinery, including automobiles, until they are reasonably
certain that therapy with ABILIFY does not affect them adversely. Body
Temperature Regulation: Disruption of the body's ability to reduce core body
temperature has been attributed to antipsychotic agents. Appropriate care is
advised when prescribing aripiprazole for patients who will be experiencing con-
ditions which may contribute to an elevation in core body temperature, e.g.,
exercising strenuously, exposure to extreme heat, receiving concomitant med-
ication with anticholinergic activity, or being subject to dehydration. Dysphagia:
Esophageal dysmotility and aspiration have been associated with antipsychotic
drug use. Aspiration pneumonia is a common cause of morbidity and mortality
in elderly patients, in particular those with advanced Alzheimer's dementia.
Aripiprazole and other antipsychotic drugs should be used cautiously in patients
at risk for aspiration pneumonia (see PRECAUTIONS: Use in Patients with
Concomitant Illness). Suicide: The possibility of a suicide attempt is inherent in
psychotic illnesses, and close supervision of high-risk patients should accompa-
ny drug therapy. Prescriptions for ABILIFY should be written for the smallest
quantity of tablets consistent with good patient management in order to reduce
the risk of overdose. Use in Patients with Concomitant Illness: Safety Experience
in Elderly Patients with Psychosis Associated with Alzheimer's Disease: In a flex-
ible dose (2 to 15 mg/day), 10-week, placebo-controlled study of aripiprazole in
elderly patients (mean age: 81.5 years; range: 56 to 95 years) with psychosis
associated with Alzheimer's dementia, 4 of 105 patients (3.8%) who received
ABILIFY died compared to no deaths among 102 patients who received placebo
during or within 30 days after termination of the double-blind portion of the
Downloaded
study. Three offrom https:/www.cambridge.org/core.
the patients New York
(age 92, 91, and 87 years) died following the University, on 03 Feb 2017 at 16:21:16, subject to the Cambridge Core
https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S1092852900019118
discontinuation of ABILIFY in the double-blind phase of the study (causes of
years) died following hip surgery while in the double-blind portion of the study.
The treatment-emergent adverse events that were reported at an incidence of
>5% and having a greater incidence than placebo in this study were accidental
injury, somnolence, and bronchitis. Eight percent of the ABIUFY-treated patients
reported somnolence compared to one percent of placebo patients. In a small
dementia, ABILIFY was associated in a dose-related fashion with somnolence.
The safety and efficacy of ABILIFY in the treatment of patients with psychosis
associated with dementia have not been established. If the prescriber elects to
treat such patients with ABILIFY, vigilance should be exercised, particularly for
the emergence of difficulty swallowing or excessive somnolence, which could
predispose to accidental injury or aspiration. Clinical experience with ABILIFY in
patients with certain concomitant systemic illnesses (see CLINICAL PHARMA-
COLOGY: Special Populations: Renal Impairment and Hepatic Impairment) is
limited. ABILIFY has not been evaluated or used to any appreciable extent in
patients with a recent history of myocardial infarction or unstable heart disease.
Patients with these diagnoses were excluded from premarketing clinical studies.
information to review issues to be discussed with patients for whom they
prescribe ABILIFY (aripiprazole).
Drug-Drug Interactions: Given the primary CNS effects of aripiprazole, caution
should be used when ABILIFY is taken in combination with other centrally acting
drugs and alcohol. Due to its ai-adrenergic receptor antagonism, aripiprazole
has the potential to enhance the effect of certain antihypertensive agents.
Potential for Other Drugs to Affect ABILIFY: Aripiprazole is not a substrate of
enzymes. Aripiprazole also does not undergo direct glucuronidation. This sug-
gests that an interaction of aripiprazole with inhibitors or inducers of these
enzymes, or other factors, like smoking, is unlikely. Both CYP3A4 and CYP2D6
are responsible for aripiprazole metabolism. Agents that induce CYP3A4
(e.g., carbamazepine) could cause an increase in aripiprazole clearance and
lower blood levels. Inhibitors of CYP3A4 (e.g., ketoconazole) or CYP2D6 (e.g.,
quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and
cause increased blood levels. Ketoconazole: Coad ministration of ketoconazole
(200 mg/day for 14 days) with a 15-mg single dose of aripiprazole increased the
AUC of aripiprazole and its active metabolite by 63% and 77%, respectively. The
effect of a higher ketoconazole dose (400 mg/day) has not been studied. When
concomitant administration of ketoconazole with aripiprazole occurs, aripipra-
zole dose should be reduced to one-half of its normal dose. Other strong
inhibitors of CYP3A4 (itraconazole) would be expected to have similar effects and
need similar dose reductions; weaker inhibitors (erythromycin, grapefruit juice)
have not been studied. When the CYP3A4 inhibitor is withdrawn from the
combination therapy, aripiprazole dose should then be increased. Quinidine:
Coadministration of a 10-mg single dose of aripiprazole with quinidine
(166 mg/day for 13 days), a potent inhibitor of CYP2D6, increased the AUC of
aripiprazole by 112% but decreased the AUC of its active metabolite, dehydro-
aripiprazole, by 35%. Aripiprazole dose should be reduced to one-half of its nor-
mal dose when concomitant administration of quinidine with aripiprazole occurs.
Other significant inhibitors of CYP2D6, such as fluoxetine or paroxetine, would
be expected to have similar effects and, therefore, should be accompanied by
similar dose reductions. When the CYP2D6 inhibitor is withdrawn from the com-
bination therapy, aripiprazole dose should then be increased. Carbamazepine:
Coadministration of carbamazepine (200 mg BID), a potent CYP3A4 inducer, with
aripiprazole (30 mg Qp) resulted in an approximate 70% decrease in Cmax and
AUC values of both aripiprazole and its active metabolite, dehydro-aripiprazole.
When carbamazepine is added to aripiprazole therapy, aripiprazole dose should
be doubled. Additional dose increases should be based on clinical evaluation.
When carbamazepine is withdrawn from the combination therapy, aripiprazole
dose should then be reduced. No clinically significant effect of famotidine, val-
proate, or lithium was seen on the pharmacokinetics of aripiprazole (see CLINI-
CAL PHARMACOLOGY: Drug-Drug Interactions). Potential for ABILIFY to Affect
Other Drugs: Aripiprazole is unlikely to cause clinically important pharmacoki-
netic interactions with drugs metabolized by cytochrome P450 enzymes. In in
vivo studies, 10- to 30-mg/day doses of aripiprazole had no significant effect on
metabolism by CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19
(omeprazole, warfarin), and CYP3A4 (dextromethorphan) substrates. Additionally,
aripiprazole and dehydro-aripiprazole did not show potential for altering
CYP1 A2-mediated metabolism in vitro (see CLINICAL PHARMACOLOGY: Drug-
Drug Interactions). Alcohol: There was no significant difference between
aripiprazole coadministered with ethanol and placebo coadministered with
ethanol on performance of gross motor skills or stimulus response in healthy
subjects. As with most psychoactive medications, patients should be advised to
avoid alcohol while taking ABILIFY. Carcinogenesis, Mutagenesis, Impairment
Pregnancy Category C: There are no adequate and well-controlled studies in
pregnant women. It is not known whether aripiprazole can cause fetal harm
when administered to a pregnant woman or can affect reproductive capacity.
Aripiprazole should be used during pregnancy only if the potential benefit out-
weighs the potential risk to the fetus. Labor and Delivery: The effect of arip-
iprazole on labor and delivery in humans is unknown. Nursing Mothers:
Aripiprazoie was excreted in milk of rats during lactation. It is not known whether
aripiprazole or its metabolites are excreted in human milk. It is recommended
that women receiving aripiprazole should not breast-feed.
Pediatric Use: Safety and effectiveness in pediatric and adolescent patients
have not been established. Geriatric Use: Of the 5592 patients treated with
aripiprazole in premarketing clinical trials, 659 (12%) were >65 years old and
525 (9%) were >75 years old. The majority (91 %) of the 659 patients were diag-
nosed with dementia of the Alzheimer's type. Placebo-controlled studies of arip-
iprazole in schizophrenia did not include sufficient numbers of subjects aged 65
and over to determine whether they respond differently from younger subjects.
There was no effect of age on the pharmacokinetics of a single 15-mg dose of
aripiprazole. Aripiprazole clearance was decreased by 20% in elderly subjects
no detectable effect of age in the population pharmacokinetic analysis in schiz-
ophrenia patients. Studies of elderly patients with psychosis associated with
Alzheimer's disease, have suggested that there may be a different tolerability
profile in this population compared to younger patients with schizophrenia (see
PRECAUTIONS: Use in Patients with Concomitant Illness). The safety and effica-
cy of ABILIFY in the treatment of patients with psychosis associated with
Alzheimer's disease has not been established. If the prescriber elects to treat
such patients with ABILIFY, vigilance should be exercised.
ADVERSE REACTIONS
Aripiprazole has been evaluated for safety in 5592 patients who participated in
multiple-dose premarketing trials in schizophrenia, bipolar mania, and dementia
of the Alzheimer's type, and who had approximately 3639 patient-years of expo-
sure. Adverse Findings Observed in Short-Term, Placebo-Controlled Trials of any drug-seeking behavior, these observations were not systematic and it is not
Patients with Schizophrenia The following findings are based on a pool of five
placebo-controlled trials (four 4-week and one 6-week) in which aripiprazole
was administered in doses ranging from 2 to 30 mg/day. Adverse Events
Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlledand such patients should be observed closely for signs of ABILIFY misuse or
Trials: Overall, there was no difference in the incidence of discontinuation due to
adverse events between aripiprazole-treated (7%) and placebo-treated (9%)
patients. The types of adverse events that led to discontinuation were similar
between the aripiprazole and placebo-treated patients. Adverse Events
Occurring at an Incidence of >2% Among Aripiprazoie-Treated Patients and
Greater than Placebo in Short-Term, Placebo-Controlled Trials: Treatment-emer-
gent adverse events that occurred during acute therapy (up to 6 weeks) at an
incidence of 2% or more of patients treated with aripiprazole (doses >2 mg/day)
and for which the incidence was greater than the incidence reported for place-
bo were: BodyasaWhole—headache, asthenia, and fever; Digestive System —
nausea, vomiting, and constipation; Nervous System — anxiety, insomnia, light-
headedness, somnolence, akathisia, and tremor; Respiratory System — rhinitis
and coughing; Skin and Appendages — rash; Special Senses — blurred vision. ©2003 Otsuka Pharmaceutical Co, Ltd, Tokyo, 101-8535 Japan
Dose-Related Adverse Events: The only adverse event to have a possible
dose response relationship, and then most prominent only with 30 mg, was
somnolence (placebo, 7.7%; 15-mg, 8.7%; 20-mg, 7.5%; 30-mg, 15.3%).
Extrapyramidal Symptoms: In short-term, placebo-controlled trials, the incidence
of reported EPS for aripiprazole-treated patients was 6% vs. 6% for placebo.
Objectively collected data from those trials on the Simpson Angus Rating Scale
(for EPS), the Barnes Akathisia Scale (for akathisia), and the Assessments of
Involuntary Movement Scales (for dyskinesias) also did not show a difference
between aripiprazole and placebo, with the exception of the Barnes Akathisia
Scale (aripiprazole, 0.08; placebo, -0.05). Laboratory Test Abnormalities: A
between group comparison for 4- to 6-week placebo-controlled trials revealed
no medically important differences between aripiprazole and placebo groups in
the proportions of patients experiencing potentially clinically significant changes
in routine serum chemistry, hematology, or urinalysis parameters. Weight Gain:
In short-term trials, there was a slight difference in mean weight gain between
aripiprazole and placebo patients (+0.7 kg vs. -0.05 kg, respectively), and also
a difference in the proportion of patients meeting a weight gain criterion of >7%
of body weight [aripiprazole (8%) compared to placebo (3%)]. ECG Changes:
Between group comparisons for pooled placebo-controlled trials revealed no
significant differences between aripiprazole and placebo in the proportion of
patients experiencing potentially important changes in ECG parameters; within
the dose range of 10 to 30 mg/day, aripiprazole tended to slightly shorten the
QTC interval. Aripiprazole was associated with a median increase in heart rate of
4 beats per minute compared to a 1 beat per minute increase among placebo
patients. Other Adverse Events Observed During Clinical Trials: Following is a list
of modified C0START terms that reflect treatment-emergent adverse events
reported by patients treated with aripiprazole at multiple doses >2 mg/day dur-
ing any phase of a trial within the database of 5592 patients. It is important to
emphasize that, although the events reported occurred during treatment with
aripiprazole, they were not necessarily caused by it. Frequent events occurred in
at least 1/100 patients; infrequent events occurred in 1/100 to 1/1000 patients;
rare events in fewer than 1 /1000 patients. Body as a Whole: Frequent - flu syn-
drome, peripheral edema, chest pain, neck pain, neck rigidity; Infrequent- pelvic
pain, suicide attempt, face edema, malaise, photosensitivity, arm rigidity, jaw
pain, chills, bloating, jaw tightness, enlarged abdomen, chest tightness; Rare -
throat pain, back tightness, head heaviness, moniliasis, throat tightness, leg
rigidity, neck tightness, Mendelson's syndrome, heat stroke. Cardiovascular
System: Frequent - hypertension, tachycardia, hypotension, bradycardia;
Infrequent- palpitation, hemorrhage, myocardial infarction, prolonged QT inter-
val, cardiac arrest, atrial fibrillation, heart failure, AV block, myocardial ischemia,
phlebitis, deep vein thrombosis, angina pectoris, extrasystoles; Rare - vasovagal
reaction, cardiomegaly, atrial flutter, thrombophlebitis. Digestive System:
Frequent - anorexia, nausea and vomiting; Infrequent - increased appetite, gas-
troenteritis, dysphagia, flatulence, gastritis, tooth caries, gingivitis, hemorrhoids,
gastroesophageal reflux, gastrointestinal hemorrhage, periodontal abscess,
tongue edema, fecal incontinence, colitis, rectal hemorrhage, stomatitis, mouth
ulcer, cholecystitis, fecal impaction, oral moniliasis, cholelithiasis, eructation,
intestinal obstruction, peptic ulcer; Rare - esophagitis, gum hemorrhage, glos-
sitis, hematemesis, melena, duodenal ulcer, cheilitis, hepatitis, hepatomegaly,
pancreatitis, intestinal perforation. Endocrine System: Infrequent - hypothy-
roidism; Rare - goiter, hyperthyraidism. Hemic/Lymphatic System: Frequent -
ecchymosis, anemia; Infrequent - hypochromic anemia, leukopenia, leukocyto-
sis, lymphadenopathy, thrombocytopenia; Rare - eosinophilia, thrombocythemia,
macrocytic anemia. Metabolic and Nutritional Disorders: Frequent - weight loss,
creatine phosphokinase increased; Infrequent-dehydration, edema, hypercho-
lesteremia, hyperglycemia, hypokalemia, diabetes mellitus, SGPT increased,
hyperlipemia, hypoglycemia, thirst, BUN increased, hyponatremia, SGOT
increased, alkaline phosphatase increased, iron deficiency anemia, creatinine
increased, bilirubinemia, lactic dehydrogenase increased, obesity; flare- hyper-
kalemia, gout, hypernatremia, cyanosis, hyperuricemia, hypoglycemic reaction.
Musculoskeletal System: Frequent-musc\e cramp, /nfregue/tf-arthralgia, bone
pain, myasthenia, arthritis, arthrosis, muscle weakness, spasm, bursitis; Rare -
rhabdomyolysis, tendonitis, tenosynovitis, rheumatoid arthritis, myopathy.
Nervous System: Frequent - depression, nervousness, increased salivation,
hostility, suicidal thought, manic reaction, abnormal gait, confusion, cogwheel
rigidity; Infrequent - dystonia, twitch, impaired concentration, paresthesia,
vasodilation, hypesthesia, extremity tremor, impotence, bradykinesia, decreased
libido, panic attack, apathy, dyskinesia, hypersomnia, vertigo, dysarthria, tardive
dyskinesia, ataxia, impaired memory, stupor, increased libido, amnesia,
cerebrovascular accident, hyperactivity, depersonalization, hypokinesia, restless
leg, myoclonus, dysphoria, neuropathy, increased reflexes, slowed thinking,
hyperkinesia, hyperesthesia, hypotonia, oculogyric crisis; Rare - delirium,
euphoria, buccoglossal syndrome, akinesia, blunted affect, decreased
consciousness, incoordination, cerebral ischemia, decreased reflexes, obsessive
thought, intracranial hemorrhage. Respiratory System: Frequent - dyspnea,
pneumonia; Infrequent- asthma, epistaxis, hiccup, laryngitis; Rare - hemopty-
sis, aspiration pneumonia, increased sputum, dry nasal passages, pulmonary
edema, pulmonary embolism, hypoxia, respiratory failure, apnea. Skin and
Appendages: Frequent - dry skin, pruritus, sweating, skin ulcer; Infrequent -
acne, vesiculobullous rash, eczema, alopecia, psoriasis, seborrhea; Rare -
maculopapular rash, exfoliative dermatitis, urticaria. Special Senses:
Frequent - conjunctivitis, ear pain; Infrequent-dry eye, eye pain, tinnitus, otitis
media, cataract, altered taste, blepharitis; Rare - increased lacrimation, frequent
blinking, otitis externa, amblyopia, deafness, diplopia, eye hemorrhage,
photophobia. Urogenltal System: Frequent - urinary incontinence; Infrequent-
cystitis, urinary frequency, leukorrhea, urinary retention, hematuria, dysuria,
amenorrhea, abnormal ejaculation, vaginal hemorrhage, vaginal moniliasis, kid-
ney failure, uterus hemorrhage, menorrhagia, albuminuria, kidney calculus, noc-
turia, polyuria, urinary urgency; Rare - breast pain, cervicitis, female lactation,
anorgasmy, urinary burning, glycosuria, gynecomastia, urolithiasis, priapism.
OVERDOSAGE
Management of Overdosage: No specific information is available on the treat-
ment of overdose with aripiprazole. An electrocardiogram should be obtained in
case of overdosage and, if QTC interval prolongation is present, cardiac monitor-
ing should be instituted. Otherwise, management of overdose should concen-
trate on supportive therapy, maintaining an adequate airway, oxygenation and
ventilation, and management of symptoms. Close medical supervision and mon-
itoring should continue until the patient recovers. Charcoal ~ In the event of an
overdose of ABILIFY, an early charcoal administration may be useful in partially
preventing the absorption of aripiprazole. Administration of 50 g of activated
charcoal, one hour after a single 15 mg oral dose of aripiprazole, decreased the
mean AUC and Cmax °f aripiprazole by 50%.
DRUG ABUSE AND DEPENDENCE
Controlled Substance: ABILIFY (aripiprazole) is not a controlled substance.
Abuse and Dependence: Aripiprazole has not been systematically studied in
humans for its potential for abuse, tolerance, or physical dependence. In physical
dependence studies in monkeys, withdrawal symptoms were observed upon
abrupt cessation of dosing. While the clinical trials did not reveal any tendency for
possible to predict on the basis of this limited experience the extent to which a
CNS-active drug will be misused, diverted, and/or abused once marketed.
Consequently, patients should be evaluated carefully for a history of drug abuse,
abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior).
Marketed by Otsuka America Pharmaceutical, Inc, Rockville, MO 20850 USA
and Bristol-Myers Squibb Co, Princeton, NJ 08543 USA
Manufactured by Otsuka Pharmaceutical Co, Ltd, Tokyo, 101-8535 Japan
Distributed by Bristol-Myers Squibb Co, Princeton, NJ 08543 USA
^ Bristol-Myers Squibb Company % Otsuka America
Princeton, N| 08543 U.S.A. ™ Pharmaceutical, Inc.
D6-B001A-06-03 A4115/10-02 Revised: May 2003
terms of use, available at
!
 Original Research
• ^ continued from page 740

presented in Table 2. Self-rated trauma is generally reported abuse: sexual abuse (%2=6.11, df=l, P=.O13) physical abuse
by subjects with cluster A and B diagnoses, and is reported (%2=5.54, df=l, P=.O19) and emotional abuse (%2=4.O3, df=l,
relatively less by subjects meeting diagnoses in cluster C. P=.045) There were no significant gender interactions for
Since gender interactions were apparent in a considerable either cluster A assignment for paranoid personality disorder.
proportion of the logistic regression analyses described below, Inspection of the correlation coefficients for abuse parameters
simple correlations for males and females, respectively, are with paranoid personality disorder suggests that these rela-
summarized in Table 3. The diagnoses represented in Tables tionships may be somewhat stronger for males than females.
2 and 3 are limited to those for which significant associations Indeed, logistic regression results for paranoid personality dis-
with trauma ratings were found using logistic regression. order confined to male subjects were as strong as for the
entire sample, for collective trauma scores (%2=17.75, df=5,
Prediction of Cluster Diagnoses Using Specific P=.OO3), and for the three measures of abuse (physical:
Childhood Trauma Questionnaire Subscale Scores X2=6.55, df=l, P=.010; sexual: X2=6.51, df=l, P=.011; and
Trauma scores were significant predictors of a cluster A emotional abuse: %2=4-03, df=l, P=.045). As an explanation
diagnosis (%z=11.97, df=5, P=.O35). Individual predictors for the lack of findings pertaining to paranoid personality dis-
were sexual (%2=7.58, df=l, P=.OO6) and physical abuse order using the cruder measure of threshold severity based on
(%2=4-37, df=l, P=.O37). Among the diagnoses that comprise total C T Q score, the mean CTQ score (equivalent to the
cluster A, only paranoid disorder showed a significant associa- sum) was not significantly correlated with paranoid personal-
tion with childhood trauma scores (%2=18.81, df=5, P=.OO2) ity disorder, because emotional and physical neglect had neg-
with significant specific associations for all three measures of ative associations with the disorder, offsetting the significant
positive associations with sexual and physical abuse. Global
measures, therefore, may obscure important relationships
Male(n=118)
Females (n=64) apparent at more refined levels of observation.
There was no significant association of trauma variables
with the presence of a cluster B diagnosis, despite the finding
of an association with the threshold rating based on the
CTQ total score. There was, however, a significant gender
interaction for sexual abuse and cluster B membership
reflecting the significant prediction, among males only, of a
Emotional Physical Sexual Emotional Physical cluster B diagnosis by sexual (%2=4-56, df=l, P=.O33) and
Abuse Abuse Abuse Neglect Neglect
physical abuse (x 2 =4.06, df=l, P=.O44). Among cluster B
diagnoses, only antisocial personality disorder showed signifi-
FIGURE 1. Percent of Subjects Meeting CTQ cant associations with trauma scores, considered collectively
Threshold Criteria for Abuse and Neglect (%2=11.32, df=5, P=.O45), and specifically, with physical
CTQ=Childhood Trauma Questionnaire. abuse (%2=7.71, df=l, P=.OO5) and sexual abuse (%2=6.83,
Bierer LM, Yehuda R, Schmeidler J, Mitropoulou V, New AS, Silverman JM, df=l, P=.OO9). Since only two women in this sample were
Siever L. CNS Spectr. Vol 8, No 10. 2003.
assigned a diagnosis of antisocial personality disorder, inter-
actions with gender could not be evaluated. In analyses lim-
ited to males, results similar to those for cluster B were found
• Cluster A (n=92)
• Cluster B (n=94) for antisocial personality disorder, for all trauma predictors
D Cluster C(n=115) (X2=13.73 df=5, P=.017), and for sexual (x 2 =7.46, d/=l,
P=.OO6) and physical abuse (x2=6.91, d/=l, P=.OO9).
No significant associations were apparent for any trauma
variable with BPD, but several gender interactions were pre-
sent for individual trauma predictors. As for antisocial person-
ality disorder, the only significant findings were in males, for
whom emotional abuse was a significant predictor (%2=6.89,
df=l, P=.OO9), with trend findings for sexual abuse (%2=3.69,
-2.5
EA PA SA EN PN
df=l, P=.O55), and for emotional (%2=2.93, df=l, P=.O87) and
physical neglect (x2=2.90, df=l, P=.O88). For women, there
FIGURE 2. Differences in Mean CTQ Subscale Scores for were non-significant negative correlations of all trauma sub-
Subjects With and Without Cluster A, B, and scales with both borderline diagnosis and cluster B assignment,
C Diagnoses offsetting the positive associations present for males, and
CTQ=Childhood Trauma Questionnaire; EA=emotional abuse; PA=physical explaining the lack of findings for the total sample.
abuse; SA=sexual abuse; EN=emotional neglect; PN=physical neglect.
Lastly, for cluster C membership, there was a significant
Bierer LM, Yehuda R, Schmeidler J, Mitropoulou V, New AS, Silverman JM,
Siever L. CNS Spectr. Vol 8, No 10. 2003.
association with all trauma items (%2= 14.08, df=5, P=.015),
and specifically, with physical (%2= 8.74, d/=l, P=.OO3) and

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 Original Research

emotional abuse (x2=5.77, df=l, P=.O16). Unlike clusters A
and B, in cluster C, having higher trauma scores was associ-
ated with the relative absence, rather than the presence of
each diagnosis (that is, "relative absence" in comparison
with other personality disorder subjects for whom, as a group,
increased trauma scores are found [Table 2 and Figure 2]).
Specific findings are not presented for diagnoses within clus-
ter C since negative associations do not indicate which dis-
orders may be present among subjects identified for the
absence of a specified diagnosis.
Predictors of Suicide and Self-Harm
Prediction of suicide attempt history approached statisti-
cal significance for trauma variables considered collectively
(%2= 10,62, df=5, P=.O59), with emotional abuse being the
only significant specific predictor (%2=8.02 , d/=l, P=.005).
Significant gender interactions were not apparent for either
suicide attempts or self-mutilation. The five trauma dimen-
sion scores significantly predicted suicidal behavior in men
(%2=11.21, df=5, P=.O47), whereas in women, emotional
abuse predicted suicide history (%2=5.61, df=l, P=.O18).
History of self-mutilation was not predicted by collective
trauma scores in either gender, but was predicted by emo-
tional abuse significantly in men (x2=3.94, df=l, P=.O47).
Results for suicide attempts and self-mutilation were similar
when additionally controlling for lifetime history of major
depressive disorder.
DISCUSSION
While trauma exposure was represented in - 8 0 % of this
personality disorder sample, only a few distinct relationships
were shown for the associations of specific trauma dimensions
with individual personality disorders or clusters. Sexual and
physical abuse, however, were relatively important predictors of
antisocial and paranoid personality disorders, with relationships
to antisocial personality disorder being somewhat more robust.
Paranoid personality disorder was additionally predicted by
childhood emotional abuse. Contrary to expectations, BPD did

TABLE 1. DISTRIBUTION OF AXIS 1 AND AXIS II DIAGNOSES ACCORDING TO GENDER

Total Male Female

(n=182) (n=118) (n=64)
Diagnosis N (%) N (%) N (%) X2(ctf=D P

Axis I
Major depressive disorder 30 (24.2) 19(22.1) 11 (28.9) 0.68 NS
Bipolar-type II 33(18.1) 18(15.3) 15 (23.4) 1.87 NS
Cyclothymia 14(7.7) 6(5.1) 8(12.5) 3.21 NS
PTSD* 30 (24.2) 19(22.1) 11 (28.9) 0.68 NS
Other anxiety disorders: 66 (36.3) 41(34.7) 25 (39.1) 0.34 NS
Social anxiety disorder 21(11.5) 15(12.7) 6 (9.4) 0.45 NS
Panic anxiety disorder 20(11) 12(10.2) 8(12.5) 0.23 NS
Simple phobia 20(11) 8 (6.8) 12(18.8) 6.08 .014
Obsessive-compulsive disorder 19(10.4) 13(11.0) 6 (9.4) 0.12 NS

Axis II
Cluster A 92 (50.5) 61 (66.3) 31 (33.7) 0.18 NS
Paranoid 57(31.3) 35 (29.7) 22 (34.4) 0.43 NS
Schizoid 23 (12.6) 21 (17.8) 2(3.1) 8.09 .009
Schizotypal 48 (26.4) 36 (30.5) 12(18.8) 2.96 .086
Cluster B 94(51.6) 56 (59.6) 38 (40.4) 2.36. NS
Histrionic 35(19.2) 17 (14.4) 18(28.1) 5.03 .025
Antisocial 17 (9.3) 15(12.7) 2(3.1) 4.50 .034
Borderline 71 (39) 39(33.1) 32 (50) 5.01 .025
Narcissistic 31(17) 21(17.8) 10(15.6) 0.14 NS
Cluster C 115(63.2) 75 (63.6) 40 (34.8) 0.02 NS
Obsessive-compulsive disorder 39(21.4) 28 (23.7) 11(17.2) 0.06 NS
Dependent 20(11) 8 (6.8) 12(18.8) 6.08 .014
Avoidant 55 (30.2) 36 (30.5) 19(29.7) 0.01 NS
Passive-aggressive 36(19.8) 24 (20.3) 12(18.8) 0.07 NS
Not otherwise specified 16 (8.8) 11 (9.3) 5 (7.8) 0.12 NS

Attempted suicide* 43 (23.8) 11(9.4) 32(50) 37.65 <.0005

Self-mutilation 40 (22) 15(12.7) 25 (39.1) 16.80 <,0005
* Research diagnosis for PTSD only performed in a subset of subjects (n=130)
f
Suicide attempt history unavailable for one male subject (n=181)
NS=non-significant; PTSD=posttraumatic stress disorder.
BierertM, Yehuda R, Schmeidler J, Mitropoulou V, New AS, Silverman JM, Siever L. CNS Spectr. Vol 8, No 10. 2003.

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 Original Research

not tend to be as strongly associated with either abuse parame-
ter, and was significantly predicted by emotional abuse only in
men, and to a lesser extent (trend findings) by sexual abuse,
and emotional and physical neglect.
The latter result contrasts with the positive finding for
BPD using a global threshold severity rating as the predictor.
History of suicide attempts or gestures, a diagnostic criterion
for BPD, was predicted by emotional abuse in the entire sam-
ple, and was as well in women subjects considered separately.
In men, emotional abuse proved a significant predictor of
self-mutilatory behaviors, a more direct correlate of BPD.
To the degree that suicidality and self-mutilation can be
interpreted as indices of degree of severity, perhaps particu-
larly among borderline subjects, history of emotional abuse
was a more salient predictor of borderline pathology1925 than
either sexual or physical abuse. That we interpret the associ-
ations found with BPD in this series to reflect severity of ill-
ness, rather than specific determinants, is consistent with the
findings of Bernstein and colleagues39 using the CTQ who
reported emotional abuse to be a broad risk factor for person-
ality disorder expression.
Quite generally, physical and sexual abuse appear in this
sample as antecedent traumatic occurrences in disorders with
externally directed psychopathology (paranoid and antiso-
cial personality disorders), whereas emotional abuse was
principally associated with a disorder characterized by affec-
tive instability and impulse dyscontrol, often expressed as
self-directed aggressive behaviors (ie, BPD). These associa-
tions were strongest, and indeed, only significant for analyses
limited to men. While the disproportionate number of men
in the current study represents a contribution to a literature
comprised of studies based predominantly on female samples,
it presents a limitation with respect to gender-specific
inferences. The analytic strategies that were employed, how-
ever, accounted for this, and as well for uneven gender distri-
butions within specific personality disorder diagnoses, and
across trauma ratings. The sporadic findings in which the
relative absence of a diagnosis was predicted are a conse-
quence of the analytic strategy in which comparisons are
confined within the cohort of personality disorder subjects,
and do not include an unaffected comparison group.
Without exception in this study, even significant associa-
tions of childhood trauma variables with personality disorder
diagnoses were not large. The most substantial correlations
represented were in males, respectively, for antisocial person-
ality disorder with physical (0.27) and sexual abuse (0.26),
and physical neglect (0.25), followed by correlations for
paranoid personality disorder diagnosis with sexual (0.24)
and physical abuse (0.24). These results are similar to those
reported by Modestin and colleagues40 who studied the rela-
tionship of physical and sexual abuse to personality disorder
diagnoses in 90 consecutively admitted subjects to an inpa-
tient psychiatry ward, of whom 43 (20 males) met criteria for
axis II diagnoses. In that series, the association of physical
and/or sexual abuse with paranoid personality disorder
(r=.34) was greater than that with BPD diagnosis (r=.26),
with both correlations strengthened by the inclusion of sub-
jects not meeting diagnostic criteria for personality disorders
in the analysis.
Fossatti and colleagues41 performed a meta-analysis of
21 studies published between 1980 and 1995 in which a
mean pooled r (used as an index of effect size) of 0.28 was
found for the association of childhood sexual abuse with
BPD diagnosis, reflecting data from -2,500 subjects. As the
majority of the studies reviewed in the latter analysis were
derived from inpatient samples, there is a strong likelihood

TABLE 2. SIGNIFICANT PARTIAL CORRELATIONS OF CTQ 1MEASURES ACCORDING T O PERSONALITY

DISORDER (DF=1 79]

Emotional Physical Sexual Emotional Physical Mean

Diagnostic Abuse Abuse Abuse Neglect Neglect Score
Group n % r P r P r P r P r P r P
Cluster A 92 50.5 .115 NS .172 .021 .216 .004 -.051 NS .034 NS .134 .071
Paranoid 57 31.3 .137 .065 .181 .015 .173 .020 -.099 NS -.035 NS .105 NS

Cluster B 94 51.6 .103 NS .073 NS -.014 NS .042 NS .042 NS .070 NS

Histrionic 35 19.2 .036 NS .067 NS -.068 NS -.059 NS -.099 NS -.026 NS
Antisocial 17 9.3 .072 NS .214 .004 .138 .065 .024 NS .146 .049 .155 .037
Borderline 71 39.0 .273 .089 .024 NS .026 NS .083 NS .061 NS .091 NS

Cluster C 115 63.2 -.179 .016 -.236 .001 -.094 NS -.070 NS .028 NS -.163 .028
Avoidant 55 30.2 -.097 NS -.169 .023 -.034 NS -.000 NS .047 NS -.078 NS
Passive 36 19.8 -.142 .057 -.091 NS -.034 NS -.162 .029 .014 NS -.125 .093
-aggressive
Attempted 43 23.8 .041 NS .207 .005 .033 NS .088 NS .109 NS .141 .059
suicide*
Self 40 22.0 -.047 NS .124 .096 .023 NS .028 NS .051 NS .054 NS
mutilation
* Attempted suicide unavailable for one male subject (n=117)
CTQ=Childhood Trauma Questionnaire; NS=non-significant.
Bierer LM, Yehuda R, Schmeidler J, Mitropoulou V, New AS, Silverman JM, Siever L CNSSpectr. Vol 8, No 10. 2001

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 Original Research

that contributors to severity of illness, including history of
childhood abuse and neglect, are well represented. The
authors interpreted this pooled r as indicating a lack of sup-
port for consideration of sexual abuse as a critical antecedent
of BPD, a finding consistent with the results of the current
study. Collectively, these results speak to the necessity of
including additional factors, including genetic and constitu-
tional predispositions, to descriptive models of personality
disorder pathogenesis.
That childhood trauma variables may be differentially
associated with cluster assignments is effectively illustrated
in Figure 2. The heuristic value of this distribution, however,
is dependent on the construct validity of the cluster formula-
tions as they are now conceived. Paranoid interpretations or
projections are likely to be elicited and sustained in the ser-
vice of affect regulation, identity stabilization, and may actu-
ally delay impulsive action. In the current series, for
instance, factor analyses did not conform to the generally
accepted cluster distribution of diagnoses (data not shown).
Further, significant proportions of subjects with paranoid dis-
order diagnoses (cluster A) were also diagnosed respectively
with antisocial and BPDs (both cluster B). The similarity of
the relationships of childhood physical and sexual abuse to
both paranoid and antisocial personality disorders, and to a
lesser extent to BPD, suggests that these disorders may share
at least some behavioral characteristics related to similar
adverse childhood exposures.
Diagnoses, rather than behavioral dimension scores, were
used as the dependent measures for analysis in this study.
This procedure may have obscured the demonstration of
associations between childhood trauma variables and char-
acter traits.1033'42 That personality disorder subjects typically
meet criteria for more than one diagnosis43 (in this study,
-2.5 diagnoses), simply underscores the need for broadly

TABLE 3. SIGNIFICANT CORRELATIONS OF CTQ MEASURES WITH MALE AND FEMALE

PERSONALITY DISORDER SUBJECTS

Emotional Physical Sexual Emotional Physical Mean

Diagnostic Percent Abuse Abuse Abuse Neglect Neglect Score
Group n (%) r P r P r P r P r P r P
Males (n=118)
Cluster A 61 51.7 .091 NS .056 .092 .132 NS -.069 NS .047 NS .093 NS
Paranoid 35 29.7 .172 .062 .238 .009 .243 .008 -.099 NS -.047 NS .140 NS
Cluster B 56 47.5 .160 .083 .154 .095 .193 .036 .100 NS .124 NS .201 .029
Histrionic 17 14.4 .064 NS .047 NS .102 NS -.002 NS -.030 NS .051 NS
Antisocial 15 12.7 .104 NS .265 .004 .263 .004 .002 NS .249 .007 .222 .016
Borderline 39 33.1 .225 .014 .092 NS .188 .042 .172 .063 .188 .041 .241 .008
Cluster C 75 63.6 -.150 NS -.236 .010 -.032 NS -.009 NS .061 NS -.120 NS
Avoidant 36 30.0 -.088 NS -.171 .064 .002 NS .059 NS .091 NS -.044 NS
Passive 24 20.3 -.067 NS -.130 NS .002 NS -.032 NS .060 NS -.060 NS
-aggressive
Attempted 11 9.4 .152 NS -.052 NS .141 NS .006 NS -.042 NS .062 NS
suicide
Self mutilation 15 12.7 .193 .036 .048 NS .006 NS .065 NS .089 NS .124 NS

Females (n=64)
Cluster A 31 48.4 .061 NS .200 NS .318 .010 -.018 NS .011 NS .197 NS
Paranoid 22 34.4 .072 NS .081 NS .134 NS -.101 NS -.014 NS .055 NS
Cluster B 38 59.4 -.013 NS -.077 NS -.203 NS -.064 NS -.104 NS -.127 NS
Histrionic 18 28.1 -.007 NS .096 NS -.189 NS -.138 NS -.195 NS -.115 NS
Antisocial 2 3.1 -.036 NS .076 NS .013 NS .103 NS -.169 NS .011 NS
Borderline 32 50.0 -.056 NS -.093 NS -.105 NS -.065 NS -.149 NS -.117 NS
Cluster C 40 62.5 -.236 .060 -.235 .062 -.161 NS -.175 NS -.031 NS -.228 .070
Avoidant 19 29.7 -.115 NS -.165 NS -.072 NS -.106 NS -.030 NS -.129 NS
Passive 12 18.8 -.293 .019 -.017 NS -.072 NS -.400 .001 -.070 NS -.227 .071
-aggressive
Attempted 32 50.0 .290 .020 .141 NS .061 NS .220 .080 .112 NS .212 .092
suicide
Self 25 39.1 .038 NS -.165 NS .042 NS .037 NS -.056 NS -.016 NS
mutilation
* Data not available for one subject (n=181)
t Data not available for one subject (n=117)
NS=non-significant.
Bierer LM, Yehuda R, Schmeidler J, vlitropoulou V, New AS, Silverman JM, Siever L. C7VS Spectr. Vol 8, No 10.2003.

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applied dimensional descriptors in this population. It is likely
that some, if not several characteristic symptoms of BPD are
shared among individuals meeting diagnostic criteria for
other disorders, suggested by the overlap among paranoid,
antisocial, and borderline disorders. Another example is the
correlation of dependent personality disorder, controlling for
gender, with both BPD (r=.162, P=.O3O) and self-mutilatory
behaviors (r=.24O, P=.OO1).
The suggestion that childhood exposure to emotional
abuse and neglect is shared among the personality disorders
generally, but that sexual and physical abuse, or severe forms
of neglect, function as determinants of clinical severity
across several diagnoses, is highly appealing, and seems to
account for the discrepant results that are increasingly
emerging in the literature.15'21'3844 Clinical samples, particu-
larly those selected from inpatient services, are biased toward
severity, and may reflect the consequences of extreme exam-
pies of exposure, possibly atypical of the majority of subjects.
Results based on these samples may for this reason find a
central association of sexual or physical abuse with border-
line or other personality disorders. In the current series,
physical and sexual abuse were more directly related to para-
noid and antisocial personality disorder, and emotional abuse
to borderline diagnoses (albeit in men only, or indirectly,
with measures of suicidality). This statement, however,
should be interpreted with due appreciation that these three
dimensions of abuse are highly intercorrelated, and measure-
ment of one dimension, or a finding relating to it, will also
have application to other forms of associated abuse. The
experience in childhood of sustained emotional abuse and
neglect is in no way specific for the expression of personality
disorder psychopathology, and has been shown to confer risk
for a range of psychological sequelae, including depressive
and anxiety spectrum disorders, with or without comorbid
axis II pathology.7
The relatively elevated ratings for emotional abuse and
neglect, in comparison to the "reportable" indices of abuse
and physical neglect, among the personality disorder subjects
in this study places findings reported for sexual and physical
abuse into context. These more extreme and easily rated
behaviors take place in environments of verbal harangue,
criticism, demoralization, emotional withdrawal, abandon-
ment, and inconstancy. However, the modest associations of
personality disorder diagnoses with any measure of trauma,
found in this and other studies, suggest that childhood
trauma exposure is only one contributor to the disposition
toward personality disorder development.44 IS££I
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