Journal of Personality Disorders, 34, Special Issue, 6–24, 2020
© 2020 The Guilford Press
NARCISSISTIC AND BORDERLINE
PERSONALITY DISORDERS:
RELATIONSHIP WITH OXIDATIVE STRESS
Royce J. Lee, MD, David Gozal, MD, MBA, Emil F. Coccaro, MD,
and Jennifer Fanning, PhD
The authors hypothesized that personality disorders characterized by
interpersonal hypersensitivity would be associated with an elevated
concentration of 8-hydroxy-2'-deoxyguanosine (8-OH-DG), the oxidized
form of guanine, and a biomarker of oxidative stress burden. One hundred
ninety-five male and female adults underwent semistructured diagnostic
interviews, completed questionnaire measures of social cognition and
emotional attribution, and had blood drawn for determination of
plasma 8-OH-DG. A hierarchical linear regression model revealed that
narcissistic and borderline personality disorders predicted 8-OH-DG level
independently of the effects of age, gender, recent alcohol and cigarette
use, current major depression, and posttraumatic stress disorder. In all
subjects, 8-OH-DG level was also correlated with the number of borderline
personality disorder symptoms present. Narcissistic and borderline
personality disorders predicted oxidative stress burden independently of
potentially confounding factors.
Keywords: borderline personality disorder, narcissistic personality disorder,
oxidative stress, 8-OH-DG, stress, emotion, disgust, personality disorder
Personality disorders remain a challenging group of disorders to treat. There
are no FDA-approved treatments for these disorders, in part due to a lack of
understanding of their underlying biological mechanism. Progress has been
made using scientific approaches such as high-resolution brain imaging (Kimmel et al., 2016), neuroendocrinology (Lee et al., 2012), and measures of
neurotransmitter function (Coccaro et al., 1989). The results of this work
generally point to altered neurophysiological indices of stress reactivity in
personality disorder as related to transdiagnostic dimensions such as affective
instability, trauma exposure, and aggression.
From the Department of Psychiatry and Behavioral Neuroscience, The University of Chicago (R. J. L.,
E. F. C.); the Department of Child Health, University of Missouri School of Medicine, Columbia, Missouri (D. G.); and the Center for Depression, Anxiety, and Stress, Harvard Medical Hospital, Belmont,
Massachusetts (J. F.).
Address correspondence to Royce J. Lee, MD, The University of Chicago, Department of Psychiatry and
Behavioral Neuroscience, 5841 S. Maryland Ave., MC 3077, Chicago, IL 60637. E-mail: rlee@yoda.bsd.
uchicago.edu
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NPD, BPD, AND OXIDATIVE STRESS
7
With respect to categorical diagnostic constructs, neurobiological
research to date has been primarily focused on borderline personality disorder (BPD). Narcissistic personality disorder (NPD) has received less attention. One consequence of this is that psychological models of narcissism
are not yet integrated with neurobiological models. This is likely of some
importance, because phenotypic controversies have led to lack of consensus
on nosology (Ronningstam, 2013). As an important example, neuroimaging research has provided unexpected evidence of hyperreactivity in highly
narcissistic individuals of the social pain network (Cascio, Konrath, & Falk,
2013; Jauk, Benedek, Koschutnig, Kedia, & Neubauer, 2017) and the motor
mimicry network (Marcoux et al., 2014) during social interaction tasks.
These findings raise important questions about the relationship between NPD
and near-neighbor conditions such as antisocial and borderline personality
disorders. NPD appears to be situated between these disorders, sharing on
the one hand features of callousness with antisocial personality disorder
(Gunderson & Ronningstam, 2001; Wilson, Stroud, & Durbin, 2017) and, on
the other, showing excessive social reactivity, or interpersonal hypersensitivity, as has been proposed to underlie BPD (Gunderson & Lyons-Ruth, 2008;
Ronningstam, 2013). Interpersonal hypersensitivity is a conceptual model of
borderline psychopathology that posits that a biological vulnerability in the
child disrupts early attachment to caregivers, whose negative responses are
internalized by the child and carried into adulthood as a habitually aversive
social interaction style. Supportive evidence of the construct in BPD is broad,
although the construct is complex and there is not consensus on how it is
best measured. For example, individuals with BPD experience more anger
and emptiness in response to social interactions when compared to individuals with other personality disorders (Stepp, Pilkonis, Yaggi, Morse, & Feske,
2009). The outward grandiosity of narcissism seems at first glance to be
inconsistent with the interpersonal hypersensitivity construct, but there is
evidence that it may apply. Suicide attempts by individuals with NPD have
been found to be preceded by recent relationship problems and being fired
from a job (Blasco-Fontecilla et al., 2010). Interactions of grandiosity and
vulnerability predict rejection sensitivity in individuals with NPD (Roche,
Pincus, Conroy, Hyde, & Ram, 2013). While grandiose narcissism and vulnerable narcissism have been found to differ, as expected, on dimensions of
agency and domination, both subtypes have been found to be associated with
lower levels of warmth and communion in their interpersonal relationships,
pointing to the kinds of attachment problems that are at the core of the
interpersonal hypersensitivity construct (J. D. Miller, Price, Gentile,Lynam, &
Campbell, 2012). Neurobiological research may help to shed some light on
these issues by revealing commonalities and differences between personality
disorder subtypes.
One understudied area of research in personality disorder is oxidative
stress, the production and accumulation of reactive oxygen species (ROS) in
the brain and body through metabolic processes. Although interconnected
with what is generally considered to be the stress response system centered on
the hypothalamic-pituitary-adrenal axis, oxidative stress is a largely cellular
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8
LEE ET AL.
process (Schiavone, Jaquet, Trabace, & Krause, 2013). Social stressors relevant
to personality disorder, such as maternal deprivation, social defeat, and social
deprivation, have been found to increase oxidative stress (Markovic et al.,
2017; Schiavone et al., 2009; Solanki, Salvi, Patki, & Salim, 2017). We have
previously found that impulsive aggression and the presence of personality
disorder are both associated with increased oxidative stress, as evidenced by
elevated blood levels of 8-hydroxy-2'-deoxyguanosine (8-OH-DG; Coccaro,
Lee, & Gozal, 2016). 8-OH-DG is the oxidized form of the nucleoside guanine, derived from mitochondrial and nuclear DNA (Evans, Olinski, Loft, &
Cooke, 2010). As measured in peripheral blood, its concentration reflects the
balance between the production of oxidative free radicals (H202) and their
removal by intrinsic antioxidant activity. Oxidized guanine is mutagenic: It
causes transcription errors, leading to carcinogenesis (Hayakawa et al., 1999),
and is thus of interest on its own as a risk factor for cancer. Thus, elevated
concentration of 8-OH-DG is a biomarker of endogenous oxidative stress
load (Valavandis, Vlachogianni, & Fiotakis, 2009).
Whether specific personality disorders are associated with oxidative stress
is an important question. Given a previous literature linking social stress and
oxidative stress, we hypothesized that in a sample of adults with and without
a range of personality disorders recruited for transdiagnostic research studies
from the community, personality disorders previously associated with interpersonal hypersensitivity (narcissistic and borderline) would be associated
with higher oxidative stress. To explore the relationship between oxidative
stress and interpersonal hypersensitivity, we assessed the relationship between
oxidative stress and two vignette-based instruments measuring hostility and
emotional reactivity.
METHODS
SUBJECTS
All research procedures were approved by the institutional review board (IRB)
of the Biological Sciences Division at The University of Chicago. Subjects provided written, informed consent using IRB-approved consent forms. Research
volunteers came from the general population of the Chicago metropolitan area
using media advertisements recruiting for transdiagnostic research studies
that included personality disordered, depressed, anxious, and healthy adults.
The sample comprised 68 normal controls, 29 psychiatric controls, and 98
personality disordered subjects (N = 195). Psychiatric controls met diagnostic
criteria for one or more current or past psychiatric disorders but did not have
a personality disorder. The psychiatric control group included 2 subjects with
a current intermittent explosive disorder, 1 with an impulse control disorder,
15 with an anxiety disorder, 2 with current depression, 2 with a current adjustment disorder, 1 with an eating disorder, 2 with a past alcohol (EtOH) disorder,
and 16 with a past anxiety disorder. Age and gender distributions across the
three groups of subjects are described in Table 1. Subjects with a personality
disorder met criteria for 1–6 disorders, with a mean of 1.38 disorders.
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02_G4784_471.indd 9
25 12.3)
28 (13.8)
ObsessiveCompulsive
PD NOS
12 (42.9)
14 (56)
2 (66.7)
27 (62.8)
7 (31.8)
—
—
11
(55)
34.68 (7.082)
34.56 (62.5)
26.0 (7.0)
34.80 (7.311)
36.33 (8.643)
34.95 (8.759)
—
—
34.5 (9.058)
35.76 (6.26)
32 (9.08)
12.1954
(3.915)
12.550
(4.690)
11.885
(4.795)
15.940
(7.312)
15.19
16.091
(4.488)
14.537
(5.966)
14.95
(4.507)
—
—
13.398
(3.626)
10.826
(4.45)
10.874
(4.801)
Mean Age, years 8-OH-DG
(SD)
M(SD)
PD NOS: personality disorder not otherwise specified.
16 (7.9)
15 (7.4)
Narcissistic
Avoidant
0
43 (21.2)
Borderline
1 (0.5)
22 (10.8)
Antisocial
3 (1.5)
0
Schizotypal
Histrionic
0
Schizoid
Dependent
3 (20)
20 (9.9)
Paranoid
19 (65.5)
29
Psychiatric
Controls
35
(52.2)
68
Female,
n (%)
Normal
Controls
n (%)
4.609
(2.205)
4.816
(2.317)
5.79
(2.709)
6.167
(3.753)
11.5
5.679
(2.577)
5.924
(2.173)
6.222
(2.34)
—
—
6.750
(2.277)
4.111
(2.105)
3.046
(1.85)
Hostile
Attribution
M(SD)
8.391 (1.576)
8.143 (2.032)
8.615 (1.192)
9.0 (1.0)
7.0
8.357 (1.392)
8.543 (2.020)
8.611 (1.754)
—
—
8.800 (1.373)
8.370 (1.305)
7.71 (1.863)
Instrumental
Attribution
M(SD)
6.304
(2.363)
4.952
(2.479)
5.154
(2.577)
5.667
(4.933)
3.0
5.643
(2.590)
5.086
(2.769)
5.611
(3.146)
—
—
5.400
(3.112)
6.222
(2.621)
6.804
(2.385)
Benign
Attribution
M(SD)
TABLE 1. Descriptive Information
7.667
(2.259)
8.143
(1.852)
9.307
(2.175)
8.333
(3.215)
9.0
7.429
(2.681)
9.086
(2.020)
9.5
(1.654)
—
—
10.200
(2.277)
6.889
(2.512)
6.02
(2.154)
Angry
Affect
M(SD)
6.875
(2.401)
6.905
(2.644)
9.154
(2.076)
9.0
(2.646)
12.0
6.857
(2.825)
8.428
(2.367)
7.944
(2.531)
—
—
8.600
(2.230)
6.519
(2.751)
5.50
(2.71)
Embarrassed
Affect
M(SD)
98.818
(9.333)
97.632
(9.051)
100.80
(8.417)
115
86.0
89.167
(24.033)
96.273
(12.028)
92.333
(11.873)
—
—
90.0
(22.511)
96.519
(12.014)
98.863
(15.29)
Socially
Appropriate
Response
M(SD)
52.546
(11.775)
52.444
(14.694)
56.4
(13.385)
37
—
54
(14.588)
62.0
(17.208)
71.0
(17.094)
—
—
60.375
(15.315)
47.926
(12.615)
44.824
(13.502)
Aggressive
Response
M(SD)
55.455
(14.654)
54.611
(12.33)
60.5
(12.103)
55
—
54.636
(12.484)
65.524
(14.299)
70.455
(13.344)
—
—
60.250
(14.330)
53.519
(12.148)
47.294
(14.775)
Relationally
Aggressive
Response
M(SD)
NPD, BPD, AND OXIDATIVE STRESS
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LEE ET AL.
DIAGNOSTIC PROCEDURE
Axis I and II diagnoses were made using DSM-IV-TR criteria (American
Psychiatric Association [APA], 2000) based on information gathered during
semistructured interviews (Structured Clinical Interview for DSM [SCID; First,
Spitzer, Gibbon, & Williams, 1997] and Structured Interview for the Diagnosis
of DSM Personality Disorder [SID-P; Pfohl, Blum, & Zimmerman, 1997]).
SCID and SID-P interviews were conducted by clinicians with a master’s
or doctoral degree in clinical psychology. Clinical raters underwent training
and verification of reliability by random, video-recorded interview and confirmation of reliability. Final diagnosis was made by a consensus procedure
in which all available clinical data were compiled in a report and reviewed
by a committee that included the research psychiatrist and the clinical raters
(Coccaro, Nayyer, & McCloskey, 2012).
ELIGIBILITY CRITERIA
Eligibility criteria excluded subjects with current medical illness, fever, recent
injury, clinical signs of inflammation on physical examination, and positive
urine drug screen and/or alcohol breathalyzer test. All subjects were between
the ages of 18 and 55. Subjects with a history of psychotic disorder (schizophrenia, bipolar mania with psychosis) and acute suicidality were excluded.
8-OH-DG ASSAY
In subjects meeting eligibility criteria, whole blood was obtained by phlebotomy, anticoagulated with EDTA, centrifuged, and stored at −80°C until
batch assay. The 8-OH-DG level was measured in duplicate by a commercially
available immunoassay (Cayman Chemical; Ann Arbor, MI; detection lower
limit = 30 pg/mL; coefficients of variation < 9.2%). Reported measures represented the mean of duplicate assay results.
INTERPERSONAL HYPERSENSITIVITY
There are not yet questionnaire measures specific to the interpersonal
hypersensitivity construct in personality disorder, which includes elements
of disorganized attachment, aggression, and affective disturbance (Bureau,
Easlerbrooks, & Lyons-Ruth, 2009; Lyons-Ruth, Melnick, Patrick, & Hobson, 2007). Exploratory analyses were undertaken to do preliminary work in
this area. Two instruments were selected that assess social behavior by eliciting the direct response of the subject to social cues. The Social Information
Processing Questionnaire (SIP-Q; Coccaro, Noblett, & McCloskey, 2009;
see also Coccaro, Fanning, Keedy, & Lee, 2016) is a self-report questionnaire
that assesses attributional style, emotional response, and response selection
in response to a series of eight vignettes depicting interpersonal conflict in
which the intent of the antagonist is ambiguous. The first four vignettes depict
acts of relational aggression such as social exclusion, while the second four
vignettes depict physical aggression. In response to each vignette, subjects select
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NPD, BPD, AND OXIDATIVE STRESS
11
an attribution of hostile intent (the antagonist intends to do harm to the relationship or body), instrumental intent (you are in the way of another goal), or
benign intent (the antagonist makes an understandable mistake). The subject
then indicates an emotional response (anger or embarrassment) and identifies
his or her own likely response in the situation: aggressive response (striking
back), relationally aggressive (e.g., silent treatment), or socially appropriate
(making an overture). Consistent with social information processing theory
of reactive aggression (Crick & Dodge, 1996), the SIP-Q shows convergent
validity with measures of interpersonal hostility and childhood trauma and
divergent validity with personality measures such as the Trait Meta-Mood
Scale (TMMS; Coccaro et al., 2009).
The Emotional Attribution Questionnaire (EAQ), modified from previous
work in patients with brain injuries and impaired social behavior (Blair &
Cipolotti, 2000), is a series of 68 brief vignettes describing a variety of social
and nonsocial events in which the subject is asked to identify the emotional
reaction of the vignette’s protagonist. For the example, subjects are asked to
assign an emotional response (angry, happy, fear, disgust, sad) that “Tania” feels
in response to the statement, “Tania was told that if she painted the woman’s
face, she would receive $100. But after the job was done, the woman only gave
her $50.” Responses are scored as correct or incorrect. Scores are calculated
for each depicted mood state. Lower scores indicate poorer recognition of
the particular affect depicted. Performance on the task has been found to be
impaired in subjects with acquired abnormalities in sympathetic nervous tone,
which is thought to interfere with “bottom-up” detection of affective states
(Heims, Critchley, Dolan, Mathias, & Cipolotti, 2004) and in a sociopathic
patient with lesions to the orbitofrontal cortex (Blair & Cipolotti, 2000).
STATISTICAL ANALYSIS
Personality disorder diagnoses (DSM-IV-TR; APA, 2000) were assessed as
predictors of 8-OH-DG using hierarchical linear regression analysis. Because
levels of oxidative stress have been previously associated with age (Maehira,
Nakama, Ohmine, & Miyagi, 2004), male sex, smoking (Black, Bot, Scheffer,
& Penninx, 2016), drinking (Caimi, Carollo, & Lo Presti, 2003; Götz et al.,
2001; Micallef, Lexis, & Lewandowski, 2007), major depressive disorder
(Black, Bot, Scheffer, Cuijpers, & Penninx, 2015), and posttraumatic stress
disorder (PTSD) (M. W. Miller & Sadeh, 2014), these were included in the
model. Of note, 22 subjects met criteria for a current depressive episode, and 20
subjects met criteria for current PTSD. In the second step, personality disorder
diagnosis was entered if the sample size was more than 10 subjects per diagnosis, coded as a 0 (absent) or 1 (present). For patients who met criteria for more
than one personality disorder diagnosis, each diagnosis was accounted for in
the model. To assess dimensional relationships between personality disorder
symptoms and 8-OH-DG, a separate hierarchical linear regression model was
assessed entering the number of personality disorder criteria from the SID-P
endorsed by the subject for each personality disorder category in the second
step, in place of the categorical diagnoses. Dimensional relationships between
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12
LEE ET AL.
8-OH-DG and interpersonal hypersensitivity were tested using hierarchical
linear regression models.
RESULTS
8-OH-DG values were inspected by histogram, which showed a near-normal
distribution (mean = 12.242 pg/mL, SD = 5.020) but with a single, univariate outlier with an 8-OH-DG level of 34.63 pg/mL, greater than 4 standard
deviations above the mean. The Kolmogarov–Smirnov (KS) test confirmed
nonnormality (KS = .070, df = 196, p = .02). The single outlier was a patient
with BPD and no other personality disorder. Exclusion of the outlier reduced
the KS test to nonsignificance. Although the value is biologically plausible and
in line with the hypothesized relationship between BPD and oxidative stress,
all reported analyses excluded the univariate outlier. Exclusion of this subject
did not significantly impact the linear regression model.
The hierarchical linear regression model for 8-OH-DG based on personality disorder diagnosis found that NPD and BPD predicted variance in this
oxidative stress measure, even when accounting for other important sources.
The first model included factors previously associated with oxidative stress
burden, including age, gender, EtOH consumption, smoking, current major
depression, and current PTSD, F(6, 195) = 5.780, p < .001 (Table 2). Male
gender and recent alcohol use were associated with 8-OH-DG. The personality disorders with n > 10 included borderline (n = 43), narcissistic (n = 15),
antisocial (n = 22), paranoid (n = 20), avoidant (n = 16), obsessive-compulsive
(OCPD; n = 25), and personality disorder not otherwise specified (NOS) (n
= 28). Addition of the personality disorder diagnoses resulted in an overall
model that predicted variance in 8-OH-DG, F(13, 195) = 4.339 p < .001,
with a significant F-change statistic, F(8, 181) = 2.779, p = .009, compared
to the model without personality disorder diagnoses. Of the seven personality disorders, only BPD (β = 3.439, p = .001; R2 = .054) and NPD (β = 3.731
p = .006; R2 = .049) significantly predicted 8-OH-DG after accounting for
potential confounding variables.
Both BPD and NPD remain significant predictors after Bonferroni correction for multiple measures (p = .021 and p = .042, respectively; see Figure 1). The plot of predicted × actual 8-OH-DG values (Figure 2) confirmed
normality and linearity. The plot of predicted values × residuals was unbiased
and homoscedastic (Figure 3). Variation inflation factor (VIF) values for the
personality disorder predictors ranged from 1.117 (OCPD) to 1.715 (antisocial personality disorder), ruling out problematic levels of multicollinearity
in the predictors.
Results of the hierarchical linear regression model for 8-OH-DG based
on the count of personality disorder criteria/symptoms in the entire sample
found that adding the count of personality disorder symptoms for borderline,
narcissistic, paranoid, antisocial, avoidant, and obsessive-compulsive personality disorder resulted in a significant model as well as a significant F-change
statistic (see Table 3). The effects were not due to age, sex, major depressive
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02_G4784_471.indd 13
.000
.994
−.343
−.031
.072
−.019
−.048
−.013
−.002
.198
.294
.095
.010
−.098
.233
−.280
.049
Standardized
Beta
.958
1.269
1.310
1.018
1.347
1.339
.984
1.157
1.089
.794
.020
.679
.41
SE
1.038
−.270
−.589
−.192
−.023
2.768
3.495
1.415
.146
−1.438
3.387
−4.007
.706
t
.300
.787
−.589
.848
.992
.006
.001
.159
.884
< .152
.001
< .001
.132
Sig.
1.140
1.225
1.598
1.172
1.763
1.208
1.684
1.080
1.127
1.030
1.059
1.095
1.065
VIF
Note. Sex (male = 1, female = 2), current major depression (No = 0, Yes = 1), current PTSD (No = 0, Yes = 1), borderline and other personality disorders (No = 0, Yes = 1).
MDD = major depressive disorder; PTSD = posttraumatic stress disorder; OCPD: obsessive-compulsive personality disorder; PD NOS = personality disorder not otherwise
specified; Sig. = significance; VIF = variation inflation factor. Bold text indicates statistically significant associations.
PD NOS
−.772
.083
−.019
Paranoid
Avoidant
−.195
.197
3.731
.028
3.439
1.523
.038
Antisocial
.009
OCPD
2.779
.234
.182
.159
−1.142
.068
.146
−.050
.268
.029
−2.720
.223
.486
< .001
β
Borderline
< .001
7.780
Sig. F Zero-Order
Change Correlation
Narcissistic
Model 2
PTSD
MDD
Smoking
Drinks/week
4.339
(13,194)
.128
F Change
.132
.394
Adjusted R
Square
−.276
< .001
R
Age
5.780
(5,194)
Sig.
Sex
Model 1
F
TABLE 2. Hierarchical Linear Regression Model of 8-OH-DG Based on Personality Disorder Diagnosis
NPD, BPD, AND OXIDATIVE STRESS
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14
LEE ET AL.
FIGURE 1. 08-OH-DG level by diagnostic group.
FIGURE 2. Expected vs. observed probabilities for 8-OH-DG.
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NPD, BPD, AND OXIDATIVE STRESS
15
FIGURE 3. Scatterplot of residual vs. predicted values for 8-OH-DG.
disorder (MDD), EtOH consumption, and recent smoking. Only the count of
BPD symptoms emerged as a significant predictor of 8-OH-DG after accounting for age, sex, EtOH consumption, recent smoking history, MDD, and PTSD
(β = .727, p = .001) (see Figure 4).
Exploratory analyses were conducted to examine the relationship between
8-OH-DG levels and dimensional measures of social cognition. For the SIP-Q,
a model predicting 8-OH-DG that included hostile attribution, benign attribution, instrumental attribution, anger response, and embarrassed response
did not result in a statistically significant change in F value when added to
gender, age, recent EtOH consumption, smoking, current depression, and
PTSD. A second linear regression analysis that included response selection
as predictors of 8-OH-DG produced a significant model, F(8, 142) = 2.787,
p = .005, and F-change statistic, F(3, 134) = 2.744, p = .046. Of the three
responses, only a relationally aggressive response predicted 8-OH-DG at a
statistically significant level (β = .113, p = .02), but the finding did not survive
Bonferroni correction. For the EAQ, the hierarchical linear regression model
including the five emotional attributions resulted in a significant model, F(11,
130) = 3.685, p < .001, accounting for variance in 8-OH-DG level above and
beyond gender, age, recent EtOH consumption, smoking, current depression,
and PTSD, F change (5, 119) = 4.313, p = .001. Correct attribution of sadness
(β = .750, p = .029) and fear (β = 2.263, p = .020) was positively correlated
with 8-OH-DG, but neither survived Bonferroni correction. Correct attribution of disgust was negative correlated with 8-OH-DG (β = −1.730, p = .001),
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02_G4784_471.indd 16
.223
.057
#Paranoid
#Avoidant
−.333
.100
.115
−.134
−.035
.030
.035
.326
.150
.382
−.083
.010
−.099
.234
−.277
.048
Standardized
Beta
.257
.348
.257
.326
.244
.206
.771
1.092
.796
.020
.682
.041
SE
.445
..288
.445
−1.302
1.791
3.549
−1.236
.134
−1.449
3.388
−3.952
.691
t
.657
.773
.657
.194
.124
<.001
.218
.894
.149
.001
<.001
.491
Sig.
1.498
2.720
1.498
2.615
1.728
2.852
1.168
1.126
1.029
1.059
1.064
1.095
VIF
Note. Sex (male = 1, female = 2), current major depression (No = 0, Yes = 1), current PTSD (No = 0, Yes = 1), #Borderline = number of criteria met. MDD = major
depressive disorder; PTSD = posttraumatic stress disorder; OCPD: obsessive-compulsive personality disorder; Sig. = significance; VIF = variation inflation factor. Bold
text indicates statistical significance.
.154
#OCPD
.436
.730
−.952
.036
−.424
< .001
#Antisocial
5.015
.146
−1.153
.069
−2.694
.028
β
.028
.301
.211
.268
−.052
.312
.506
< .001
Zero Order
Correlation
#Narcissistic
< .001
5.689
Sig. F
Change
#Borderline
Model 2
PTSD
MDD
Smoking
Drinks/week
5.714
.127
F Change
.130
.392
Adjusted R
Square
−.273
< .001
R
Sex
5.689
Sig.
Age
Model 1
F
TABLE 3. Hierarchical Linear Regression Model of 8-OH-DG Based on Personality Disorder Severity
16
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NPD, BPD, AND OXIDATIVE STRESS
17
FIGURE 4. Scatterplot of 8-OH-DG and borderline personality disorder severity.
surviving Bonferroni correction (see Table 4). The VIF statistic for disgust was
1.380, indicating acceptable levels of collinearity.
DISCUSSION
We report that levels of the oxidative stress marker 8-OH-DG are associated
with the diagnosis of NPD and BPD after controlling for age, gender, smoking, alcohol use, depression, and PTSD. These findings support the hypothesis
that personality disorders characterized by interpersonal hypersensitivity are
associated with increased oxidative stress. The lack of association of 8-OHDG with paranoid and antisocial personality disorder does not support the
alternative hypothesis that personality disorders characterized by hostility are
associated with oxidative stress, although statistical power to rule out was
Type II error is lacking due to the relatively small sample sizes of individual
personality disorder diagnoses. Consistent with a dimensional model of BPD,
there is a positive correlation between 8-OH-DG and the number of BPD
criteria met, but not with narcissistic criteria.
This is the first such report identifying a relationship between oxidative
stress and narcissistic and borderline personality disorders. If replicated, the
findings would provide a new insight into the neurobiology of two disorders
that remain incompletely understood. Such findings would also suggest a
close biological relationship between them. Oxidative stress is an important
pathophysiological component of many medical illnesses (Betteridge, 2000)
and has been investigated predominantly in this context. Although there has
02_G4784_471.indd 17
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02_G4784_471.indd 18
.750
.094
Happy
.308
−1.730
..035
−.307
.139
.215
.190
.369
−.214
.079
Standardized
Beta
.729
.523
.272
.962
.340
.048
.050
.027
SE
.423
−3.306
1.672
2.353
2.208
2.349
−1.315
.928
t
.673
.001
.097
.020
.029
.020
.191
.355
Sig.
Note. Sig. = significance; VIF = variation inflation factor; SIP-Q = Social Information Processing Questionnaire; EAQ = Emotional Attribution Questionnaire. Bold text indicates
statistically significant associations.
.154
−.235
Anger
Disgust
.274
.001
2.263
4.313
.029
.254
.115
.504
Sad
< .001
.113
−.067
.025
β
Fear
EAQ
3.685
.046
Zero Order
Correlation
.193
2.744
Sig. F
Change
Relationally Aggressive
Response
.102
F Change
.111
.398
Adjusted R
Square
Overtly Aggressive
Response
.005
R
.016
2.787
Sig.
Socially Appropriate
Response
SIP-Q Response Selection
F
TABLE 4. Hierarchical Linear Regression Model of 8-OH-DG Based on Interpersonal Hypersensitivity
1.066
1.380
1.101
1.335
1.335
3.901
4.170
1.136
VIF
18
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NPD, BPD, AND OXIDATIVE STRESS
19
been little research in the area of oxidative stress and personality disorder,
these findings can be understood in the context of a larger body of research
connecting psychological states and biological processes.
The findings reinforce previous findings of health problems in personality
disordered populations. NPD has previously been associated with increased
mortality due to cardiovascular disease, even after controlling for relevant
medical comorbidities (Quirk et al., 2015; Samuels, 2011). NPD is also associated with gastrointestinal conditions (Quirk et al., 2015) and generally high
health care utilization (Jackson & Burgess, 2002; Samuels, 2011). BPD has
previously been associated with nearly twice the rate of metabolic syndrome
(Kahl et al., 2013) and elevated rates of chronic pain, obesity, arthritis (Powers & Oltmanns, 2013), hypertension, arteriosclerosis, and gastrointestinal
disease (El-Gabalawy, Katz, & Sareen, 2010). Oxidative stress is implicated
in all of these chronic conditions.
Oxidative stress markers have been investigated in association with other
psychiatric conditions. Although no association with depression was found in
this study, previous research has found elevated plasma and urinary 8-OHDG in depression (Maes, Galecki, Chang, & Berk, 2011). Negative studies
have also been reported (Jorgensen et al., 2013). Data from human studies
have linked elevated markers of oxidative stress with life stressors such as
bereavement (Aschbacher et al., 2013), academic stress (Cohen, Marshall,
Cheng, Agarwal, & Wei, 2000; Gidron, Russ, Tissarchondou, & Warner, 2006),
caregiving burden, suicide attempts (Vargas et al., 2013), and psychological
stress (Lesgards et al., 2002). There is some evidence that cortisol, released by
stress, increases the production of oxidative species (Aschbacher et al., 2013;
Simsek, Yüksel, Kaplan, Uysal, & Aktas, 2016). Basic science research in animal
models of social stress confirms that aversive social contexts induce oxidative stress (Schiavone et al., 2013; Solanki et al., 2017). The cross-sectional
design of this study does not permit causal inferences to be made regarding
increased oxidative stress and borderline and narcissistic personality disorders.
Nonetheless, a plausible explanation is that neurophysiological activity drives
oxidative stress in persons with a hypersensitive neural response to social
stress. Although sources of oxidative stress outside the brain cannot be ruled
out, brain metabolism accounts for 20% of the body’s oxygen (O2) budget,
out of proportion to its mass. This is because the principal sources of oxidative
species are neural activity itself (Halliwell, 1992), intracellular energy cycling
(Cobley, Fiorello, & Bailey, 2018), nitrosamine signaling between neurons
(Finnell & Wood, 2018), and catabolism of monoamine neuromodulators
such as serotonin and norepinephrine by the mitochondrial enzyme monoamine oxidase A (MAO-A; Kolla et al., 2016). Increased neural signaling
during periods of psychological stress would thus be expected to increase the
oxidation burden. Interestingly, elevated MAO-A activity is increased in the
prefrontal cortex of individuals with BPD (Kolla et al., 2016). Upregulation
of MAO-A activity would be expected to generate oxidative species through
the oxidation of monoamine neurotransmitters and could increase circulating
8-OH-DG levels. Unfortunately, no measures of MAO-A activity were taken in
this study, and this idea remains speculative. It is also possible that the direction of causation is reverse: that oxidative stress itself drives psychopathology.
02_G4784_471.indd 19
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20
LEE ET AL.
A recent epidemiological study found that lifetime exposure to air pollution
was associated with elevated risk for personality disorder in the Danish population, accounting for important cofounders such as urbanicity (Khan et al.,
2019). In an animal model, induction of phosphodiesterase-2, which reduces
oxidative stress, remarkably had the effect of decreasing anxiety-related behaviors (Masood, Nadeem, Mustafa, & O’Donnell, 2008). These connections are
fascinating but clearly remain speculative without additional research.
Exploratory analyses revealed a possible inverse relationship between
8-OH-DG and attributions of disgust. Persons with higher levels of oxidative
stress were less likely to attribute disgust to the protagonist described in this
sample vignette: Cathy is eating her dinner when her cat throws up all over
the carpet next to her. Because no a priori hypothesis predicted this finding,
replication is needed. If replicated, this finding could shed light on a previous literature linking the emotion of disgust and NPD. Narcissism has been
associated with alexithymia to all emotions (Fossati, Somma, Pincus, Borroni,
& Dowgwillo, 2017). However, specific links have been made between narcissism and specific difficulties with identifying and attributing disgust in others
(Marissen, Deen, & Franken, 2012) and self-states of shame (Poless, Torstveit,
Lugo, Andreassen, & Sütterlin, 2018). Disgust and shame are two closely
associated, socially reciprocal emotional states (Giner-Sorolla & Espinosa,
2010). Thus, the finding of disgust avoidance may be understood in light of the
theoretical and empirical literature linking narcissism with shame. It has been
hypothesized that narcissistic individuals, in defense against hypersensitivity
to shame, have an avoidant response to it (Ronningstam & Baskin-Sommers,
2013). Empirical research has confirmed that avoidance of shame is associated
with narcissistic personality traits (Poless et al., 2018). Interestingly, induction of shame has been found to increase inflammatory cytokine markers
(Dickerson, Kemeny, Aziz, Kim, & Fahey, 2004). BPD has been found to be
associated with elevated endorsement of shame (Peters & Geiger, 2016; Winter,
Bohus, & Lis, 2017). Exactly how attributional deficits in disgust are linked
to oxidative stress remains speculative without further study.
Several limitations should be mentioned. It is possible that the findings of
a specific relationship between oxidative stress and narcissistic and borderline
personality disorders are in fact driven by issues of statistical power due to
low sample sizes. Although collinearity was not estimated to be problematic
in the statistical model, correlation between personality disorder predictors
could also reduce the ability to detect associations that were present. Some personality disorders were not assessed at all in the model (schizoid, schizotypal,
dependent), but should be included in future studies. Assay sensitivity may
have reduced power to detect subtle differences that were present. Alternative
approaches include measuring the ratio of 8-OH-DG to the unhydroxylated
base 2' deoxyguanosine (2-DG) (Bolner, Pilleri, de Riva, & Nordera, 2011). A
fully powered follow-up study is needed to rule out Type I and Type II errors,
and thus conclusions of specificity in the relationship between oxidative stress
and personality disorder subtypes would be premature. The cross-sectional
study design precludes causal inferences. If replicated, the results point to the
need for longitudinal research to establish the temporal sequence of oxidative
stress burden and personality development. Due to the exploratory nature of
02_G4784_471.indd 20
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NPD, BPD, AND OXIDATIVE STRESS
21
analyses related to the interpersonal hypersensitivity construct, formal testing
of a mediation model regarding the role of oxidative stress in the relationship
between disgust/shame and narcissistic personality disorder was not conducted. This is an important topic for future research. Finally, it is unknown
if the findings reported here reflect the relationship between a domain general
stress reactivity and borderline and narcissistic personality disorders, given
interrelationships between oxidative stress, hypothalamic-pituitary axis function, and inflammation.
In summary, preliminary evidence is reported of an association of 8-OHDG, a biomarker of oxidative stress burden, with narcissistic and borderline
personality disorders. The fact that both NPD and BPD were associated with
8-OH-DG suggests that the two disorders have a biological relationship. The
findings also have implications for dimensional models of psychopathology.
Interpersonal hypersensitivity is a promising theoretical construct that may
be a useful approach to biological studies of personality disorder.
REFERENCES
American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders
(4th ed., text rev.). Washington, DC: Author.
Aschbacher, K., O’Donovan, A., Wolkowitz,
O. M., Dhabhar, F. S., Su, Y., & Epel, E.
(2013). Good stress, bad stress and oxidative stress: Insights from anticipatory cortisol reactivity. Psychoneuroendocrinology,
38, 1698–1708. https://doi.org/10.1016/j
.psyneuen.2013.02.004
Betteridge, D. J. (2000). What is oxidative stress?
Metabolism: Clinical and Experimental, 49(2), 3–8. https://doi.org/10.1016/
S0026-0495(00)80077-3
Black, C. N., Bot, M., Scheffer, P. G., Cuijpers, P.,
& Penninx, B. W. J. H. (2015). Is depression
associated with increased oxidative stress? A
systematic review and meta-analysis. Psychoneuroendocrinology, 51, 164–175. https://
doi.org/10.1016/j.psyneuen.2014.09.025
Black, C. N., Bot, M., Scheffer, P. G., & Penninx,
B. W. J. H. (2016). Sociodemographic and
lifestyle determinants of plasma oxidative stress markers 8-OHdG and F2-isoprostanes and associations with metabolic
syndrome. Oxidative Medicine and Cellular Longevity, 2016, 7530820. https://doi
.org/10.1155/2016/7530820
Blair, R. J. R., & Cipolotti, L. (2000). Impaired social
response reversal. Brain, 123, 1122–1141.
https://doi.org/10.1093/brain/123.6.1122
Blasco-Fontecilla, H., Baca-Garcia, E., Duberstein, P., Perez-Rodriguez, M. M., Dervic, K.,
Saiz-Ruiz, J., . . . Oquendo, M. A. (2010).
An exploratory study of the relationship
between diverse life events and specific
personality disorders in a sample of suicide
02_G4784_471.indd 21
attempters. Journal of Personality Disorders,
24, 773–784. https://doi.org/10.1521/pedi
.2010.24.6.773
Bolner, A., Pilleri, M., de Riva, V., & Nordera, G.
(2011). Plasma and urinary HPLC ED determination of the ratio of 8-OHdG/2-dG in
Parkinson’s disease. Clinical Laboratory, 57,
859–866.
Bureau, J. F., Easlerbrooks, M. A., & Lyons-Ruth, K.
(2009). Attachment disorganization and
controlling behavior in middle childhood:
Maternal and child precursors and correlates. Attachment & Human Development, 11, 265–284. https://doi.org/10.1080
/14616730902814788
Caimi, G., Carollo, C., & Lo Presti, R. (2003).
Diabetes mellitus: Oxidative stress and
wine. Current Medical Research and Opinion, 19, 581–586. https://doi.org/10.1185
/030079903125002324
Cascio, C. N., Konrath, S. H., & Falk, E. B. (2013).
Narcissists’ social pain seen only in the brain.
Social Cognitive and Affective Neuroscience,
10, 335–341. https://doi.org/10.1093/scan/
nsu072
Cobley, J. N., Fiorello, M. L., & Bailey, D. M. (2018).
13 reasons why the brain is susceptible to oxidative stress. Redox Biology, 15, 490–503.
https://doi.org/10.1016/j.redox.2018.01.008
Coccaro, E. F., Fanning, J. R., Keedy, S. K., & Lee,
R. J. (2016). Social cognition in intermittent
explosive disorder and aggression. Journal of
Psychiatric Research, 83, 140–150. https://
doi.org/10.1016/j.jpsychires.2016.07.010
Coccaro, E. F., Lee, R., & Gozal, D. (2016). Elevated
plasma oxidative stress markers in individuals with intermittent explosive disorder and
3/11/2020 1:56:46 PM
22
correlation with aggression in humans. Biological Psychiatry, 79, 127–135. https://doi
.org/10.1016/j.biopsych.2014.01.014
Coccaro, E. F., Nayyer, H., & McCloskey, M. S.
(2012). Personality disorder-not otherwise
specified evidence of validity and consideration for DSM-5. Comprehensive Psychiatry, 53, 907–914. https://doi.org/10.1016/j
.comppsych.2012.03.007
Coccaro, E. F., Noblett, K. L., & McCloskey,
M. S. (2009). Attributional and emotional
responses to socially ambiguous cues: Validation of a new assessment of social/emotional
information processing in healthy adults and
impulsive aggressive patients. Journal of Psychiatric Research, 43, 915–925. https://doi
.org/10.1016/j.jpsychires.2009.01.012
Coccaro, E. F., Siever, L. J., Klar, H. M., Maurer, G.,
Cochrane, K., Cooper, T. B., . . . Davis, K. L.
(1989). Serotonergic studies in patients with
affective and personality disorders. Correlates with suicidal and impulsive aggressive
behavior. Archives of General Psychiatry, 46, 587–599. https://doi.org/10.1001/
archpsyc.1989.01810070013002
Cohen, L., Marshall, G. D., Cheng, L., Agarwal,
S. K., & Wei, Q. (2000). DNA repair capacity
in healthy medical students during and after
exam stress. Journal of Behavioral Medicine,
23, 531–544. https://doi.org/10.1023/A
:1005503502992
Crick, N. R., & Dodge, K. A. (1996). Social information-processing mechanisms in reactive and
proactive aggression. Child Development,
67, 993–1002. https://doi.org/10.1111/j
.1467-8624.1996.tb01778.x
Dickerson, S. S., Kemeny, M. E., Aziz, N., Kim,
K. H., & Fahey, J. L. (2004). Immunological
effects of induced shame and guilt. Psychosomatic Medicine, 66, 124–131. https://doi
.org/10.1097/01.psy.0000097338.75454.29
El-Gabalawy, R., Katz, L. Y., & Sareen, J. (2010).
Comorbidity and associated severity of
borderline personality disorder and physical health conditions in a nationally representative sample. Psychosomatic Medicine,
72, 641–647. https://doi.org/10.1097/PSY
.0b013e3181e10c7b
Evans, M. D., Olinski, R., Loft, S., & Cooke, M. S.
(2010). Toward consensus in the analysis of
urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine as a noninvasive biomarker of oxidative stress. FASEB Journal, 24, 1249–1260.
https://doi.org/10.1096/fj.09-147124
Finnell, J. E., & Wood, S. K. (2018). Putative inflammatory sensitive mechanisms underlying
risk or resilience to social stress. Frontiers
in Behavioral Neuroscience, 12, 240. https://
doi.org/10.3389/fnbeh.2018.00240
First, M. B., Spitzer, R. L., Gibbon, M., & Williams,
J. B. W. (1997). Structured Clinical Interview
for DSM-IV Axis I Disorders, Clinician
02_G4784_471.indd 22
LEE ET AL.
Version (SCID-I-CV) for DSMIV. Washington, DC: American Psychiatric Press.
Fossati, A., Somma, A., Pincus, A., Borroni, S., &
Dowgwillo, E. A. (2017). Differentiating
community dwellers at risk for pathological narcissism from community dwellers at
risk for psychopathy using measures of emotion recognition and subjective emotional
activation. Journal of Personality Disorders, 31, 325–345. https://doi.org/10.1521/
pedi_2016_30_255
Gidron, Y., Russ, K., Tissarchondou, H., & Warner, J. (2006). The relation between psychological factors and DNA-damage: A critical
review. Biological Psychology, 72, 291–304.
https://doi.org/10.1016/j.biopsycho.2005
.11.011
Giner-Sorolla, R., & Espinosa, P. (2010). Social
cuing of guilt by anger and of shame by
disgust. Psychological Science, 22, 49–53.
https://doi.org/10.1177/0956797610392925
Götz, M. E., Janetzky, B., Pohli, S., Gottschalk,
A., Gsell, W., Tatschner, T., . . . Böning, J.
(2001). Chronic alcohol consumption and
cerebral indices of oxidative stress: Is there
a link? Alcoholism: Clinical and Experimental Research, 25, 717–725. https://doi
.org/10.1111/j.1530-0277.2001.tb02272.x
Gunderson, J. G., & Lyons-Ruth, K. (2008). BPD’s
interpersonal hypersensitivity phenotype:
A gene-environment-developmental model.
Journal of Personality Disorders, 22, 22–41.
https://doi.org/10.1521/pedi.2008.22.1.22
Gunderson, J. G., & Ronningstam, E. (2001). Differentiating narcissistic and antisocial personality disorders. Journal of Personality
Disorders, 15, 103–109. https://doi.org/10
.1521/pedi.15.2.103.19213
Halliwell, B. (1992). Reactive oxygen species and
the central nervous system. Journal of Neurochemistry, 59, 1609–1623. https://doi.org/10
.1111/j.1471-4159.1992.tb10990.x
Hayakawa, H., Hofer, A., Thelander, L., Kitajima, S.,
Cai, Y., Oshiro, S., . . . Sekiguchi, M. (1999).
Metabolic fate of oxidized guanine ribonucleotides in mammalian cells. Biochemistry,
23, 3610–3614. https://doi.org/10.1021/
bi982361l
Heims, H. C., Critchley, H. D., Dolan, R., Mathias,
C. J., & Cipolotti, L. (2004). Social and motivational functioning is not critically dependent on feedback of autonomic responses:
Neuropsychological evidence from patients
with pure autonomic failure. Neuropsychologia, 42, 1979–1988. https://doi.org/10.1016/j
.neuropsychologia.2004.06.001
Jackson, H. J., & Burgess, P. M. (2002). Personality
disorders in the community: Results from the
Australian National Survey of Mental Health
and Wellbeing. Part II. Relationships between
personality disorders, Axis I mental disorders and physical conditions with disability
3/11/2020 1:56:46 PM
NPD, BPD, AND OXIDATIVE STRESS
and health consultation. Social Psychiatry
and Psychiatric Epidemiology, 37, 251–260.
https://doi.org/10.1007/s001270200017
Jauk, E., Benedek, M., Koschutnig, K., Kedia, G.,
& Neubauer, A. C. (2017). Self-viewing is
associated with negative affect rather than
reward in highly narcissistic men: An fMRI
study. Scientific Reports, 7(1), 5804. https://
doi.org/10.1038/s41598-017-03935-y
Jorgensen, A., Krogh, J., Miskowiak, K., Bolwig,
T. G., Kessing, L. V, Fink-Jensen, A., . . . Jorgensen, M. B. (2013). Systemic oxidatively
generated DNA/RNA damage in clinical depression: Associations to symptom
severity and response to electroconvulsive
therapy. Journal of Affective Disorders, 149,
355–362. https://doi.org/https://doi.org/10
.1016/j.jad.2013.02.011
Kahl, K. G., Greggersen, W., Schweiger, U., Cordes, J.,
Correll, C. U., Frieling, H., . . . Moebus, S.
(2013). Prevalence of the metabolic syndrome in patients with borderline personality disorder: Results from a cross-sectional
study. European Archives of Psychiatry and
Clinical Neuroscience, 263, 205–213. https://
doi.org/10.1007/s00406-012-0339-2
Khan, A., Plana-Ripoll, O., Antonsen, S., Brandt, J.,
Geels, C., Landecker, H., . . . Rzhetsky, A.
(2019). Environmental pollution is associated with increased risk of psychiatric disorders in the US and Denmark. PLoS Biology,
17(8), e3000353. https://doi.org/10.1371/
journal.pbio.3000353
Kimmel, C. L., Alhassoon, O. M., Wollman, S. C.,
Stern, M. J., Perez-Figueroa, A., Hall, M. G.,
. . . Radua, J. (2016). Age-related parietooccipital and other gray matter changes in
borderline personality disorder: A metaanalysis of cortical and subcortical structures. Psychiatry Research: Neuroimaging,
251, 15–25. https://doi.org/https://doi.org/10
.1016/j.pscychresns.2016.04.005
Kolla, N. J., Chiuccariello, L., Wilson, A. A.,
Houle, S., Links, P., Bagby, R. M., . . . Meyer,
J. H. (2016). Elevated monoamine oxidaseA distribution volume in borderline personality disorder is associated with severity
across mood symptoms, suicidality, and cognition. Biological Psychiatry, 79, 117–126.
https://doi.org/10.1016/j.biopsych.2014.11
.024
Lee, R. J., Hempel, J., TenHarmsel, A., Liu, T.,
Mathé, A. A., & Klock, A. (2012). The neuroendocrinology of childhood trauma in
personality disorder. Psychoneuroendocrinology, 37, 78–86. https://doi.org/10.1016/j
.psyneuen.2011.05.006
Lesgards, J. F., Durand, P., Lassarre, M., Stocker, P.,
Lesgards, G., Lanteaume, A., . . . LehucherMichel, M. P. (2002). Assessment of lifestyle
effects on the overall antioxidant capacity
of healthy subjects. Environmental Health
02_G4784_471.indd 23
23
Perspectives, 110, 479–486. https://doi.
org/10 .1289/ehp.02110479
Lyons-Ruth, K., Melnick, S., Patrick, M., & Hobson,
R. P. (2007). A controlled study of hostilehelpless states of mind among borderline and
dysthymic women. Attachment & Human
Development, 9, 1–16. https://doi.org/10
.1080/14616730601151417
Maehira, F., Nakama, Y., Ohmine, N., & Miyagi, I.
(2004). Age-related changes in the oxidation–reduction characteristics and the
8-OHdG accumulation in liver, lung, brain
of SAMP1 and SAM R1. International
Congress Series, 1260, 259–262. https://doi
.org/10.1016/S0531-5131(03)01698-4
Maes, M., Galecki, P., Chang, Y. S., & Berk, M.
(2011). A review on the oxidative and nitrosative stress (O&NS) pathways in major
depression and their possible contribution
to the (neuro)degenerative processes in
that illness. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35,
676–692. https://doi.org/10.1016/j.pnpbp
.2010.05.004
Marcoux, L. A., Michon, P. E., Lemelin, S., Voisin,
J. A., Vachon-Presseau, E., & Jackson, P. L.
(2014). Feeling but not caring: Empathic
alteration in narcissistic men with high psychopathic traits. Psychiatry Research: Neuroimaging, 224, 341–348. https://doi.org/10
.1016/j.pscychresns.2014.10.002
Marissen, M. A. E., Deen, M. L., & Franken, I. H. A.
(2012). Disturbed emotion recognition in
patients with narcissistic personality disorder.
Psychiatry Research, 198, 269–273. https://
doi.org/10.1016/j.psychres.2011.12.042
Markovic, B., Radonjic, N. V, Jevtic, G., Stojkovic, T.,
Velimirovic, M., Aksic, M., . . . Petronijevic,
N. D. (2017). Long-term effects of maternal deprivation on redox regulation in rat
brain: Involvement of NADPH oxidase.
Oxidative Medicine and Cellular Longevity, 2017, 7390516. https://doi.org/10
.1155/2017/7390516
Masood, A., Nadeem, A., Mustafa, S. J., &
O’Donnell, J. M. (2008). Reversal of oxidative stress-induced anxiety by inhibition
of phosphodiesterase-2 in mice. Journal of
Pharmacology and Experimental Therapeutics, 326, 369–379. https://doi.org/10.1124/
jpet.108.137208
Micallef, M., Lexis, L., & Lewandowski, P. (2007).
Red wine consumption increases antioxidant status and decreases oxidative stress
in the circulation of both young and old
humans. Nutrition Journal, 6, 27. https://
doi.org/10.1186/1475-2891-6-27
Miller, J. D., Price, J., Gentile, B., Lynam, D. R.,
& Campbell, W. K. (2012). Grandiose and
vulnerable narcissism from the perspective
of the interpersonal circumplex. Personality
and Individual Differences, 53, 507–512.
3/11/2020 1:56:46 PM
24
https://doi.org/https://doi.org/10.1016/j.paid
.2012.04.026
Miller, M. W., & Sadeh, N. (2014). Traumatic stress,
oxidative stress and post-traumatic stress disorder: Neurodegeneration and the accelerated-aging hypothesis. Molecular Psychiatry,
19, 1156–1162. https://doi.org/10.1038/mp
.2014.111
Peters, J. R., & Geiger, P. J. (2016). Borderline personality disorder and self-conscious affect:
Too much shame but not enough guilt? Personality Disorders, 7, 303–308. https://doi
.org/10.1037/per0000176
Pfohl, B., Blum, N., & Zimmerman, M. (1997).
Structured Interview for DSM-IV Personality Disorder: SIDP-IV. Washington, DC:
American Psychiatric Press.
Poless, P. G., Torstveit, L., Lugo, R. G., Andreassen, M., & Sütterlin, S. (2018). Guilt and
proneness to shame: Unethical behaviour in
vulnerable and grandiose narcissism. Europe’s
Journal of Psychology, 14(1), 28–43. https://
doi.org/10.5964/ejop.v14i1.1355
Powers, A. D., & Oltmanns, T. F. (2013). Borderline personality pathology and chronic health
problems in later adulthood: The mediating
role of obesity. Personality Disorders: Theory, Research, and Treatment, 4, 152–159.
https://doi.org/10.1037/a0028709
Quirk, S. E., El-Gabalawy, R., Brennan, S. L., Bolton,
J. M., Sareen, J., Berk, M., . . . Williams,
L. J. (2015). Personality disorders and physical comorbidities in adults from the United
States: Data from the National Epidemiologic Survey on Alcohol and Related Conditions. Social Psychiatry and Psychiatric
Epidemiology, 50, 807–820. https://doi
.org/10.1007/s00127-014-0974-1
Roche, M. J., Pincus, A. L., Conroy, D. E., Hyde,
A. L., & Ram, N. (2013). Pathological narcissism and interpersonal behavior in daily
life. Personality Disorders, 4, 315–323.
https://doi.org/10.1037/a0030798
Ronningstam, E. (2013). An update on narcissistic
personality disorder. Current Opinion in
Psychiatry, 26(1), 102–106.
Ronningstam, E., & Baskin-Sommers, A. R. (2013).
Fear and decision-making in narcissistic
personality disorder—A link between psychoanalysis and neuroscience. Dialogues in
Clinical Neuroscience, 15, 191–201. https://
doi.org/10.1038/jid.2015.269
Samuels, J. (2011). Personality disorders: Epidemiology and public health issues. International
Review of Psychiatry, 23, 223–33. https://
doi.org/10.3109/09540261.2011.588200
Schiavone, S., Jaquet, V., Trabace, L., & Krause,
K.-H. (2013). Severe life stress and oxidative
02_G4784_471.indd 24
LEE ET AL.
stress in the brain: From animal models to
human pathology. Antioxidants & Redox
Signaling, 18, 1475–1490. https://doi.
org/10.1089/ars.2012.4720
Schiavone, S., Sorce, S., Dubois-Dauphin, M.,
Jaquet, V., Colaianna, M., Zotti, M.,
. . . Krause, K.-H. (2009). Involvement of
NOX2 in the development of behavioral
and pathologic alterations in isolated rats.
Biological Psychiatry, 66, 384–392. https://
doi.org/https://doi.org/10.1016/j.biopsych
.2009.04.033
Sims ek, S., Yüksel, T., Kaplan, İ., Uysal, C., & Aktas ,
H. (2016). The levels of cortisol and oxidative stress and DNA damage in child and
adolescent victims of sexual abuse with or
without post-traumatic stress disorder. Psychiatry Investigation, 13, 616–621. https://
doi.org/10.1016/j.jechem.2016.12.004
Solanki, N., Salvi, A., Patki, G., & Salim, S. (2017).
Modulating oxidative stress relieves stressinduced behavioral and cognitive impairments in rats. International Journal of
Neuropsychopharmacology, 20, 550–561.
https://doi.org/10.1093/ijnp/pyx017
Stepp, S. D., Pilkonis, P. A., Yaggi, K. E., Morse,
J. Q., & Feske, U. (2009). Interpersonal
and emotional experiences of social interactions in borderline personality disorder.
Journal of Nervous and Mental Disease,
197, 484–491. https://doi.org/10.1097/
NMD.0b013e3181aad2e7
Valavandis, A., Vlachogianni, T., & Fiotakis, C.
(2009). 8-hydroxy-2'-deoxyguanosine
(8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. Journal of
Environmental Science and Health Part C:
Environmental Carcinogenesis and Ecotoxicology Reviews, 27, 120–139.
Vargas, H. O., Nunes, S. O. V., De Castro, M. P., Bortolasci, C. C., Barbosa, D. S., Morimoto, H.
K., . . . Berk, M. (2013). Oxidative stress and
lowered total antioxidant status are associated with a history of suicide attempts. Journal of Affective Disorders, 150, 923–930.
https://doi.org/10.1016/j.jad.2013.05.016
Wilson, S., Stroud, C. B., & Durbin, C. E. (2017).
Interpersonal dysfunction in personality disorders: A meta-analytic review. Psychological Bulletin, 143, 677–734. https://doi.org/10
.1037/bul0000101
Winter, D., Bohus, M., & Lis, S. (2017). Understanding negative self-evaluations in borderline personality disorder—A review
of self-related cognitions, emotions, and
motives. Current Psychiatry Reports,
19(3), 17. https://doi.org/10.1007/s11920
-017-0771-0
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