Curr Psychiatry Rep (2013) 15:344
DOI 10.1007/s11920-012-0344-1
PERSONALITY DISORDERS (C SCHMAHL, SECTION EDITOR)
The Neurobiology of Empathy in Borderline Personality Disorder
Luis H. Ripoll & Rebekah Snyder &
Howard Steele & Larry J. Siever
Published online: 7 February 2013
# Springer Science+Business Media New York 2013
Abstract We present a neurobiological model of empathic
dysfunction in borderline personality disorder (BPD) to
guide future empirical research. Empathy is a necessary
component of interpersonal functioning, involving two dis-
tinct, parallel neural networks. One form of empathic pro-
cessing relies on shared representations (SR) of others’
mental states, while the other is associated with explicit
mental state attribution (MSA). SR processing is visceral
and automatic, contributing to attunement, but also emo-
tional contagion. MSA processing contributes to deliberate,
perspectival forms of empathic understanding. Empathic
dysfunction in BPD may involve hyper-reactivity of SR
networks and impairment of MSA networks. Nevertheless,
this empathic dysfunction is subtle, but contributes to inter-
personal difficulties. Interaction between genetic factors and
traumatic attachment stressors may contribute to develop-
ment of BPD, with painful attachment insecurity and
This article is part of the Topical Collection on Personality Disorders
L. H. Ripoll (*) : L. J. Siever
Department of Psychiatry One Gustave L. Levy Place,
Mount Sinai School of Medicine, Box 1230,
New York, NY 10029, USA
e-mail: Luis.ripoll@mssm.edu
L. H. Ripoll
New York Psychoanalytic Institute, New York, NY, USA
R. Snyder
Department of Psychology, Barnard College,
Columbia University, New York, NY, USA
H. Steele
Department of Psychology, New School for Social Research,
New York, NY, USA
L. J. Siever
James J. Peters VA Medical Center,
Mental Illness Research Education and Clinical Center
(MIRECC), Bronx, NY, USA
disorganization affecting SR and MSA network functioning.
Future avenues for BPD research will include developmen-
tal assessment of attachment and neurobiological function-
ing under varying conditions.
Keywords Borderline personality disorder . BPD .
Personality; Empathy . Attachment theory . Social cognition .
Aggression . Social affectivity . Neuropeptides .
Neurobiology . Psychiatry
Introduction
Empathy is the ability to understand others’ mental states,
with reference to guiding future interpersonal behavior [1,
2•]. In early childhood, empathy involves visceral recogni-
tion of mental states without fully understanding implica-
tions or regulating affective consequences [3, 4•, 5], relying
on neuronal representation of others’ feelings as they are
experienced in the self. The result is similarity in neural
activation while both experiencing and observing others
experiencing mental states. This processing involves shared
representations (SR) of mental states. Owing to similarity in
neuronal representations of self and other, such automatic
mirroring risks distress in response to others’ distress. SR
processing persists, although further neural development
supplements it. Thus, deliberate empathic processing, char-
acterized by explicit mental state attribution (MSA), pro-
gresses beyond reflexive SR processing to incorporate
perspective and context in reflective interpersonal narra-
tives. Empathic processing entails parallel, dissociable net-
works with variable relative activity.
Refractory symptoms of borderline personality disorder
(BPD) include affective instability and interpersonal dys-
function [6]. BPD symptoms may result from neurobiolog-
ical predisposition to persistent, excessive SR-based
attunement and impairment in MSA-based, empathic
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deliberation. Patients suffer from interpersonal hypersensi-
tivity [7], contributing to affectivity, impulsivity , social
dysfunction , aggression, and suicidality [8–11]. Projections
between SR networks and limbic or reward processing
regions may influence evaluations of social threat. During
interpersonal stress, dysfunctional empathic processing may
contribute to symptoms and fluctuation between idealization
and distrust.
Across theoretical orientations, BPD is defined by severe
disturbances in mentalizing about self and other [12, 13].
Severe BPD symptoms occur in the context of social threat
[7, 10, 11, 13, 14], contributing to transient episodes of
paranoia, erotomania, or dissociation; relationships marked
by projective identification and conflicted dependency;
emptiness and identity diffusion; and impulsive suicidality
or aggression [8, 12, 13]. Increasing research documents
interactions between genetic and developmental risk factors
for interpersonal dysfunction and BPD [7, 15•], but specific
neurobiological effects remain unclear. In particular, the
present model may assist in devising neurobiological assess-
ments, predicting individuals at risk for BPD and response
of refractory symptoms to therapeutic intervention.
Corroborative research shows SR processing during
laboratory tasks focused on patients’ automatic recogni-
tion of others’ pain, disgust, or basic sensorimotoric
intentions. Tasks associated with MSA research have
focused primarily on deliberate evaluation of more com-
plex emotions and intentions. BPD patients likely engage
in SR processing to greater extent and MSA processing
to lesser extent than individuals without personality dis-
orders (see Tables 1 and 2) [16•, 17•, 18–22]. Improving
empathic deliberation has become a focus of evidence-
based psychotherapy for BPD [23, 24]. A neurobiological
model of empathic processing may assist in understand-
ing mechanisms of action of treatments.
Despite extensive theoretical literature, relevant empiri-
cal research on empathy in BPD remains limited. The pres-
ent neurobiological model offers potential to bridge future
empirical research with past theory. Affective symptoms
concerning intolerance of aloneness and conflicted depen-
dency are aspects of BPD that are least likely to remit [6],
likely perpetuated by empathic dysfunction. By improving
adaptive regulation of empathic processing, particularly dur-
ing social threat, treatments may better target refractory
symptoms. Tracking effects of interventions upon neurobi-
ological functioning could elucidate specific mechanisms to
improve interpersonal resilience.
Genetic, neurocognitive, and developmental risk factors
are associated with the etiology of BPD [7, 15•, 25]. Mul-
tiple genetic factors interact with attachment stressors over
the course of development, resulting in attachment insecu-
rity and disorganization [15•]. It remains unclear whether
similar gene-by-environment interactions specifically cause
Curr Psychiatry Rep (2013) 15:344
maladaptive regulation of empathic networks. Naturalistic
functional neuroimaging paradigms [2•, 16•, 18, 22, 26] are
needed to capture real-life interpersonal functioning, to un-
derstand the effects of genes and development on empathic
processing.
In the context of genetic polymorphisms associated with
altered neuropeptide signaling, early experiences of attach-
ment insecurity may disrupt functional connectivity of em-
pathic networks. In securely-attached individuals, a gradual
shift from SR- to MSA-based empathic processing occurs
over the lifespan. By contrast, the inability to produce orga-
nized, hopeful evaluations of relationships defines attach-
ment insecurity associated with BPD [13, 27, 28]. With
genetic predisposition, attachment stressors may contribute
to SR hyper-reactivity and MSA impairment, neuropeptide
dysregulation, painful attachment insecurity, and refractory
symptoms (see Fig. 1).
Empathy
Successful interpersonal functioning requires social cue rec-
ognition, understanding context, and affect regulation [1, 29].
Empathy is defined as perceivers’ ability to understand mental
states in targets to thus guide interpersonal behavior. Empathic
accuracy leads to prosocial behavior and genuine empathic
concern [2•], but may decrease owing to psychopathology. We
distinguish two neural processes underlying empathy.
SR processing relies on visceral identification of mental
states via commonality in neural activation in both social
targets and perceivers. Thus, perceivers observing social
targets experiencing pain or disgust, performing simple,
goal-directed actions, producing emotional facial expres-
sions, and experiencing non-painful touch engage similar
limbic, paralimbic, or sensorimotor neural systems activated
when perceivers themselves experience these phenomena
[2•, 30]. ‘Mirror neuron’ research describes SR processing
as embodied simulation, with neural representations of
others’ mental states as experienced viscerally in the self
(see Table 1).
MSA research focuses on perceivers’ explicit judgments
of social targets’ intentions, thoughts, or feelings. Temporal
and parietal regions mediate shifts in perspective, and me-
dial prefrontal regions integrate semantic, contextual, and
sensory data [2•, 30–32]. In comparison to SR processing,
MSA networks are slower, explicit, and capable of inferen-
tial abstraction [2•, 30, 32, 33]. MSA processing is respon-
sible for serial adjustment of visceral, SR-based attunement
[34], predicting others’ behavior, and preventing short-
sighted decisions [35]. MSA processing is also required
for deliberate, self-relevant evaluation [31, 32], depend-
ing on the extent of inference and abstraction needed
(see Table 2) [36–38].
Curr Psychiatry Rep (2013) 15:344 Page 3 of 11, 344

Table 1 Borderline personality disorder (BPD) and the shared representation (SR) network-visceral, automatic attunement

Brain region Nonclinical findings BPD findings

Amygdala Results: perceivers observe targets posing facial
affect, resulting in similar activation in
targets experiencing and perceivers observing
emotional facial expressions [2•, 30]
Function in detection of affective salience, basic
affective processing, and facial affect recognition
Anterior dingulate Results: perceivers observe others experiencing pain,
resulting in similar activation in targets
experiencing and perceivers observing pain,
covarying with severity of pain in others [2•, 30]
Functions in regulation of pain and possibly
other affective extremes, and regulating
the affect of others’ pain on self
Anterior insula Results: perceivers observe targets’ faces or behavior
while experiencing pain or disgust, resulting in
similar activation in targets experiencing and
perceivers observing these states [2•, 30]
Functions in monitoring visceral experiences of
pain and disgust in self and others, though distinct
subregions of anterior and posterior insula
may subserve different functions
Inferior parietal lobe Results: perceivers observe others experiencing
non-painful touch, resulting in similar activation
during perceivers’ observation and targets’
experience of touch [2•, 30]
Inferior frontal gyrus Results: perceivers observe others performing simple
motor tasks, gestures, or facial expressions,
resulting in similar activation during perceivers’
observation and targets’ experience of action and
facial expression intentionality [2•, 30]
Hyper-reactivity in BPD in perception of affective
arousal for positive and negative valence [17•, 21],
aggression provocation [22], during attempts at
psychological distancing [19]; lack of habituation
associated with limitations in subjective perception of
social support (Ripoll and New, unpublished data)
Some question role of amygdala hyper-reactivity in
BPD, particularly when pooling studies of negative
valence stimuli [57]
Deficiency associated with impaired regulation
of affect in BPD [21]
Despite SR hyper-reactivity in other regions, deficient
activation in BPD may indicate a more specific
role primarily in affect-regulation rather than
empathic understanding
Hyper-reactive in BPD during affective empathy task
[16•], indicative of heightened visceral empathic
processing of salient social stimuli
Dysfunction associated with inability of BPD patients to
coax cooperation [18], although unclear whether
consisted in insula hyper-reactivity during fair offers
(especially given BPD patients insula hyper-reactivity
during general negative affective processing [57]) or
hypoactivation to unfair offers based on paradigm
Limited findings in BPD may indicate involvement only
in basic empathic processing of sensorimotor intention
Limited findings in BPD may indicate involvement only
in basic empathic processing of sensorimotor intention

Greater automaticity or deliberation in empathy is asso-
ciated with varying implementation of SR and MSA net-
works, respectively [33]. Functional connectivity of MSA
networks predicts adaptive empathic concern for others’
pain, indicative of a protective role in regulating whether
others’ distress heightens personal distress [39]. Extreme,
SR-based emotional contagion involves maladaptive attune-
ment to others’ distressing affect, leading to personal dis-
tress and autonomic arousal [1]. By contrast, perspective-
taking distinguishes between mental states in self and other,
requiring functional MSA circuitry and inhibition of SR
reactivity. Intimacy and social threat may bias empathic
processing, influencing perspective-taking or emotional
contagion. BPD patients’ interpersonal hypersensitivity [7]
may fundamentally affect perceptions of social threat,
resulting in attunement and contagion without perspective.
When confronted with either nonverbal or abstract con-
textual cues whose content conflicts with other social
information, healthy subjects demonstrate biased recruit-
ment of SR or MSA circuits, respectively [40]. This dem-
onstrates normative capacity for differential modulation of
empathic networks in order to understand aspects of the
interpersonal environment. Greater SR processing yields
heightened attention to nonverbal empathic cues, but reli-
ance on MSA processing yields contextualized empathic
judgments. Owing to empathic network dysregulation,
BPD patients may automatically attend to nonverbal cues
of questionable significance, remaining unable to engage in
contextualized empathic deliberation.
BPD Psychopathology
BPD patients engage in concrete mentalizing, impulsive
judgments , dissociative lapses [23], and have difficulty
integrating multimodal, socially-relevant information [41].
344, Page 4 of 11 Curr Psychiatry Rep (2013) 15:344

Table 2 Borderline personality disorder (BPD) and the mental state attribution (MSA) network-deliberate empathic inference

Brain region Nonclinical findings BPD findings

Posterior cingulate/precuneus
Medial prefrontal cortex
Temporo-parietal junction
Superior temporal sulcus
Results: activated when perceivers are asked to
explicitly evaluate targets in vignettes or their
associated visual or verbal social cues, when
comparing first- to third-person perspectives,
and when projecting the self into the future
or other circumstances [2•, 30, 31]
Activation associated with explicit mentalizing,
perspective-taking, processing self-relevance,
and mental prospection or navigation
Results: activated when perceivers are asked to
explicitly infer targets’ mental states from complex
cues, evaluate those considered self-similar [37]
or about versions of the self closer in time [36],
or when projecting the self into other
situations [31, 35]
Activation associated with accuracy of explicit
empathic inferences, processing self-relevance.
One of two regions most commonly involved in
perspectival inhibition of mirroring [2•, 13, 30, 91]
Results: activated when perceivers are asked to infer
whether targets have false or true beliefs, evaluate
targets’ familiarity to the perceiver, explicitly infer
mental states from cues, or projecting the self into
the future or other situations [13, 31, 91]
Activation associated with accuracy of explicit
empathic inferences, processing self-relevance.
One of two regions most commonly involved in
perspectival inhibition of mirroring [13, 91]
Results: activated when perceivers are asked to
evaluate complex, socially meaningful actions by
targets, perform explicit attributions of targets’
mental states [2•, 30]
Activation associated with accuracy of explicit
empathic inferences, processing self-relevance
During psychological distancing from affective
stimuli, BPD subjects demonstrate higher
activation [19], though relative lack of results
specific to BPD may indicate role in basic
processing of spatial perspective
Decreased in BPD during regulation of provoked
aggression [22], possibly indicating role in self-
relevant reflection or efforts to infer other’s inten-
tions, as means to regulate aggressive impulses
When paradigms do not allow opportunity for
behavioral response, rejection may provoke
mPFC hyperactivation [26], emphasizing need
to distinguish empathic understanding
from pure affect regulation.
Lack of findings in BPD may indicate a basic role
in distinguishing self and other,
establishing perspective
Decreased activity in BPD during deliberate
empathic processing [16•, 20]
During efforts at psychological distancing from
affective stimuli, BPD subjects demonstrate higher
activation [19], emphasizing need to distinguish
empathic understanding from affect regulation

Identity disturbance, impulsive aggression, affective in-
stability, and transient paranoia [8, 12] are often exacerbated
by interpersonal stressors, and empathic dysfunction may
perpetuate this pattern. A neurobiological model of em-
pathic dysfunction is crucial to future research on BPD
psychopathology.
In non-clinical subjects, social exclusion and induced
loneliness motivate perceptions of purposelessness [42],
decrease general cognitive abilities [43], activate ventral
striatal appetitive regions, and inhibit MSA networks
during empathic processing [44]. BPD may involve
similar, more intense or persistent experiences of per-
ceived exclusion, differentially affecting social reward,
cognition, and empathic processing. A persistent experi-
ence of interpersonal hypersensitivity [7] and intrapsy-
chic pain [45, 46], associated with attachment insecurity
[8, 12–14, 47], contributes to severe interpersonal dys-
function in BPD.
Known to relate to affect regulation [28], neurobiological
effects of attachment insecurity in BPD remain unclear.
Preliminary evidence suggests an association between at-
tachment insecurity, rejection sensitivity, or fearfulness of
abandonment on the one hand, and dysregulation of em-
pathic circuitry on the other [26, 48–50]. Painful attachment
insecurity may alter empathic processing through aberrant
perceptions of social threat. During interpersonal contexts
posing this risk, empathic network dysregulation may con-
tribute to a vicious cycle perpetuating BPD symptoms via
heightened SR-based attunement and less MSA-based
deliberation.
BPD patients demonstrate heightened affective empathy
and impaired cognitive empathy [51], likely corollaries of
SR hyper-reactivity and MSA impairment. They show sub-
tle impairment in recognizing others’ intentions in everyday
social interactions, correlated with intrusiveness of traumat-
ic symptoms [52]. Enduring aspects of attachment insecurity
Curr Psychiatry Rep (2013) 15:344
Fig. 1 A neurobiological model of empathic dysfunction in borderline
personality disorder (BPD). Genetic risk factors (i.e., monoamine and
neuropeptide genetic polymorphisms) interact with developmental risk
factors (i.e., maladaptive caregiving, abuse, neglect, attachment trau-
ma), leading to attachment insecurity and intrapsychic pain. The epi-
genetic mechanism of interaction deserves further research.
Intrapsychic pain and attachment insecurity may be associated with
dysregulation of endogenous opioids and oxytocin, contributing to
dysregulation of empathic networks during ambiguous or stressful
interpersonal contexts, such as rejection or perceived abandonment.
Resultant empathic dysfunction contributes to impulsive, aggressive,
affective, and interpersonal BPD symptoms, conferring greater risk for
interpersonal stressors and ultimately resulting in a chaotic, vicious
cycle perpetuating refractory affective and interpersonal symptoms
painfully intrude upon empathic processing. BPD patients
show greater SR activation and lesser MSA recruitment in
response to increasing task complexity [20]. In comparing
tasks designed to elicit automatic affective judgments with
those prompting empathic deliberation, BPD subjects show
SR hyper-reactivity and psychophysiologic arousal com-
pared to controls on the former, but recruit MSA regions
less on the latter, again correlated with intrusive severity of
BPD [16•].
In laboratory empathy paradigms, BPD patients show
subtle dysfunction primarily under conditions of heightened
social threat, ambiguity, or stimulus complexity. BPD sub-
jects demonstrate difficulty integrating stimuli of multiple
sensory modalities, associated with suspiciousness [41].
Impairment in facial affect recognition is evident primarily
for neutral faces, with impairment also associated with anger
or disgust [53•]. Thus, meta-analytic scrutiny highlights
empathic dysfunction associated with conditions of ambi-
guity or social threat. Otherwise, BPD patients perform as
well as or better than controls in the static Reading the Mind
in the Eyes Test [54] and another affect recognition task
involving Morphed Faces [55]. In more syntactically com-
plex theory of mind tasks, they show little impairment in
affective theory of mind and inconsistent evidence for im-
pairment in cognitive theory of mind [51, 56]. Unlike autistic
or schizophrenia spectrum patients, BPD patients’ empathic
Page 5 of 11, 344
dysfunction may only manifest during specific circumstances
of ambiguity, complexity, or social threat [13, 53•]. The result
is impairment in deliberate, cognitive empathy and reliance on
automatic, affective empathy.
Individual variability within BPD may depend on vary-
ing task conditions. Not all BPD patients engage in the same
type of empathic processing at all times. Mentalization-
based therapy identifies ‘psychic equivalence modes’
plagued by concrete errors in mentalizing, as well as ‘pre-
tend modes’ involving hyperactive mentalizing and mal-
adaptive abstraction [23], each implemented to a varying
degree depending on context. Thus, although some neuro-
imaging paradigms identify hypoactivation of medial pre-
frontal (MSA) regions, others show hyperactivation in
response to rejection, at least prior to judgment or interper-
sonal response [26]. Despite aforementioned evidence of SR
hyper-reactivity, BPD patients’ neural responses to negative
valence stimuli of various types include amygdala [57] or
anterior cingulate hypoactivation [21]. Nevertheless, when
evaluating positive or negative, interpersonal stimuli, BPD
patients show amygdala hyper-reactivity and lack of habit-
uation [17•]. Amygdala hyper-reactivity is also evident dur-
ing aggression provocation [22] and efforts at psychological
distancing [22]. Greater research attention is needed to parse
how differing levels of social salience and arousal differen-
tially affect empathic processing, and potential differences
in processing depending on the extent to which tasks impli-
cate affect-regulation versus empathic understanding.
Aggression
Greater rejection sensitivity motivates increasing needs for
control or belonging and aggressive responses to rejection
[58]. BPD severity correlates with rejection sensitivity, but
capacity for effortful behavioral control is protective [59].
Provoked aggression necessarily involves implicit or explic-
it empathic processing to recognize provocation as such.
Rejection-sensitive BPD patients may show SR hyper-
reactivity or impairment in regions associated with deliber-
ation or control, resulting in malevolent bias and aggressive
responses.
In BPD, impulsive aggression likely results from aberrant
mentalizing and rejection sensitivity. Rejection sensitivity is
associated with vulnerability to attentional disruption by
social threat [60]. Individuals with higher social belonging
needs demonstrate greater attention to nonverbal affective
cues, but lower empathic accuracy after rejection [61]. This
combination of heightened attunement to nonverbal cues
and impaired accuracy may reflect SR hyper-reactivity. SR
processing may be implicitly employed to protect BPD
patients from potential exclusion via attunement to nonver-
bal cues suggesting social threat. Nevertheless, reliance on
344, Page 6 of 11
SR processing also contributes to decreased accuracy and
impulsive aggression. Similarly, preoccupied attachment
classification (associated with BPD) heightens propensity
towards violence towards intimate partners specifically dur-
ing instances of partner withdrawal [62].
BPD patients produce more hostile evaluations of natu-
ralistic interpersonal interactions [63–65] and more readily
recognize anger in ambiguous facial stimuli [66]. This ma-
levolent bias suggests attunement to cues of otherwise ques-
tionable significance driven by SR hyper-reactivity. This
may be employed as protective vigilance, but also contrib-
utes to paranoia or aggression. Thus, SR hyper-reactivity
and MSA hypoactivity correlate with BPD patients’ inabil-
ity to control impulsive aggression in response to experi-
mental provocation [22].
BPD patients either repeatedly imagine hostility that is
not actually present or perceive hostile cues that others
ignore. Generally, either interpretation may be a conse-
quence of SR hyper-reactivity, and whether empathic dys-
function results in malevolent bias versus heightened
attunement could always be explained by an opposite ‘bias’
in healthy individuals’ neglecting social threat. Future re-
search will focus on differential effects of social threat on
attentional disruption or paradigms designed with subtly
controlled variations in degree of threat content.
Social Affectivity
Adolescent BPD patients show nonspecific difficulty in dis-
engaging visual attention from negative facial expressions
[67]. Overall, facial affect recognition research shows that
BPD subjects perform worst in identifying neutral affect,
attributing neutral faces with emotions not actually present,
but also demonstrate difficulty with angry and disgusted faces
[53•]. Anger and disgust constitute potential social threat, and
may specifically recruit SR networks designed to detect basic,
salient stimuli. Although controlled SR processing results in
vigilant attunement, SR hyper-reactivity in BPD may ulti-
mately diminish empathic accuracy for ambiguous or arousing
stimuli conveying social threat.
BPD subjects implicitly react to social exclusion with
greater, other-focused negative affect and less frequent, pos-
itive affect than healthy individuals [68], perhaps explained
by effects of intrapsychic pain on mentalizing [45]. This is
prominent in patients with histories of abuse or neglect [69],
contributing to implicit shame [14, 70], aversive tension,
and dissociation [71]. Intrapsychic pain may result from
interactions between genetic risk factors and attachment
stressors, contributing to attachment insecurity and dysre-
gulation of empathic networks. Empathic network dysfunc-
tion during social exclusion may thereby contribute to
negative affectivity.
Curr Psychiatry Rep (2013) 15:344
Owing to painful attachment insecurity, BPD patients are
highly alexithymic, unable to describe their own affect in
social situations [72]. BPD patients demonstrate exaggerat-
ed psychophysiological indicators of arousal and amygdala
hyper-reactivity in response to social stimuli (of positive or
negative valence) on the one hand, and blunted subjective
appraisal of these stimuli on the other [17•, 19, 21]. They
also show lack of psychophysiological and amygdala habit-
uation in response to repeated social affective stimuli, which
correlates with deficient ratings of tangibility of social sup-
port (Ripoll and New, unpublished data). Thus, BPD
patients’ SR hyper-reactivity in response to social affect
likely affects their subjective appraisal of tangible support.
Empathic network dysregulation also affects trust and
cooperation. BPD patients demonstrate differential neural
activity in SR regions during iterative economic exchange
games requiring cooperation [18], remaining unable to de-
tect adverse monetary offers and subsequently coax cooper-
ation. In this paradigm, BPD subjects do not show insula
(SR) hyper-reactivity, but lack the normative decrease in
insula activity associated with higher offers. Lacking varia-
tion in insula activity during the appraisal of offers’ poten-
tial for cooperative reward discourages subsequent
cooperation and indicates pervasive distrust. In BPD, insula
hyper-reactivity is also associated with processing negative
valence stimuli [57]. Without facial affective cues from
putative partners during cooperation games, BPD patients
rate their own behavior as unfair, whenever partners provide
adverse offers [73]. Similarly, BPD patients experience self-
reproach and rupture of cooperation when confronted with
ambiguity in relationships. Both phenomena indicate im-
pairment in empathic deliberation and appraisal of social
reward.
Theoretical descriptions of BPD patients’ reliance on
projective identification are consistent with developmental
failure to recruit MSA circuitry to perspectivally distinguish
self and other, and an ongoing reliance on SR-based attune-
ment. MSA impairment and SR hyper-reactivity may also
be associated indirectly with identity diffusion, dissociation,
and chaotic idealization and devaluation. The present model
suggests that dysregulated empathic networks may contrib-
ute to tumultuous appraisal of self and other in ambiguous,
threatening, or intimate contexts.
Neuropeptides
BPD patients demonstrate subtly dysfunctional empathic
processing, otherwise remaining exquisitely attuned to
others’ mental states. A threshold for dysregulation may be
associated with abiding intrapsychic pain and attachment
insecurity, set by complex interactions between genetics
and early attachment experiences [7, 15•]. In BPD, this
Curr Psychiatry Rep (2013) 15:344
may result in dysregulation of empathic networks, leading to
protective vigilance for potential social threat, but overall
empathic dysfunction. We hypothesize that dynamic dysre-
gulation of these networks, experienced as ongoing intra-
psychic pain, may be mediated by aberrant neuropeptide
signaling.
Reflection on romantic or maternal significant others
activates appetitive reward brain regions, rich in opioid
and oxytocin receptors, and concomitantly deactivates cir-
cuitry that overlaps heavily with MSA networks [5, 74].
With greater intimacy, SR processing heightens at the ex-
pense of MSA processing, while imagining others experi-
encing pain [75]. Intimacy and social reward affect empathic
processing, perhaps owing to heightened potential for social
threat. This may adversely affect empathic processing via
oxytocin- and opioid-responsive neuromodulation reaching
a pathological extreme in BPD, with persistent SR hyper-
reactivity and MSA impairment. Relationships may thereby
be evaluated as closely attuned but brittle, or intrusively
malevolent.
Neuropeptides may regulate MSA and SR activity
according to specific contexts and levels of potential inti-
macy or social reward [15•, 45, 76]. Developmental experi-
ence promoting attachment insecurity may interfere with
empathic network regulation by influencing endogenous
opioid or oxytocin neurotransmission. As a result of neuro-
peptide dysregulation, BPD patients reflexively implement
SR networks and remain unable to engage in MSA-based
deliberation.
Endogenous opioid signaling is associated with consum-
matory reward, affiliative behavior, and regulation of phys-
ical pain [77]. At baseline, BPD patients evidence decreased
physical pain sensitivity, contrasting with heightened intra-
psychic pain [45]. Moreover, opioid dysregulation, particu-
larly in SR and reward processing regions, is associated
specifically with affective instability in BPD [46]. More-
over, BPD subjects demonstrate diminished opioid tone at
baseline and dysregulation with sadness induction. Opioid
dysregulation may account for links between interpersonal
dysfunction and impulsive self-injury in BPD [45]. In BPD
subjects, experimental application of pain results in down-
regulation of SR regions otherwise hyper-reactive to affec-
tive stimuli [78]. In parallel and consistent with many pos-
sible psychological functions subserved by self-injury [79],
neurobiologically, self-injury may thus dampen intrapsychic
pain and SR hyper-reactivity.
Oxytocin coordinates affiliative behavior, mediates trust,
and regulates stress [80]. Exogenous administration
increases biases in moral decision-making, benefiting those
considered similar to oneself and derogating those consid-
ered dissimilar [81, 82] and motivating prosocial behavior
towards the former [83]. Oxytocin improves empathic accu-
racy in individuals with autistic symptoms [84] and heightens
Page 7 of 11, 344
positive recollections of maternal attachment figures in indi-
viduals reporting less attachment anxiety, while those report-
ing high attachment anxiety remember their mothers as less
caring when given oxytocin [85]. Effects of oxytocin on
parental aggression or altruism are similarly moderated by
parents’ own history of supportive caregiving [86, 87]. Oxy-
tocin administration attenuates social stress-induced dyspho-
ria in BPD patients reporting childhood trauma, lower self-
esteem, and attachment insecurity [88]. Nevertheless, BPD
patients administered oxytocin cooperate less during an eco-
nomic exchange game, an effect driven by attachment anxiety
[89]. Oxytocin may increase intimacy and diminish arousal,
but also decrease empathic deliberation, diminishing negative
affectivity while paradoxically exacerbating interpersonal
dysfunction.
Limited, conflicting, evidence exists for oxytocin or opi-
oid medications as treatment of BPD. Differences in attach-
ment history and other personality and situational
differences moderate effects of oxytocin [76]. Patients’ clin-
ical response to opioid administration may also differ
depending on genetic, developmental, or situational factors,
as well as past exposure to opioids. Clinical use of neuro-
peptides is further complicated by the complexity and po-
tential trade-off of concomitantly altering social reward
processing and empathic accuracy. Future neuropeptide re-
search must combine several methodologies to further char-
acterize empathy and interpersonal functioning in BPD:
assessment of attachment and genetic factors, experimental
administration of neuropeptides or manipulation of social
threat, and imaging of neuropeptide signaling.
Developmental Neurobiology
BPD is a result of interactions between genetics and envi-
ronment [7, 15•]. Functional impairment in synthetic neuro-
biological systems may serve as predisposition, interacting
with adverse early experiences to yield attachment insecu-
rity and metacognitive impairment [25]. Behavioral [3] and
neurobiological evidence [90] indicates an early role for SR
processing in infant empathic processing. Reciprocal co-
regulation of arousal by parent and infant ideally build upon
SR-based mirroring with increasingly symbolic reflection
[3, 5].
The ability to inhibit imitative behavior is associated with
effective empathic deliberation [91], and inhibition of SR
networks may be necessary for MSA recruitment. Perspec-
tival decoupling of neural representations of self and others,
and homeostatic affect regulation are necessary in order to
progress beyond reflexive attunement [92, 93] to develop
coherent empathic concern [94]. SR activity decreases from
childhood to middle age in response to observations of
others’ experiences of pain, with changes in insula activation
344, Page 8 of 11
further indicating shifts from visceral to abstract empathic
processing [4•]. Age-related increases in activation of prefron-
tal MSA regions [4•, 95] are associated with increasing social
abstraction.
As a likely result of interactions between genetic and
neurocognitive factors with early caregiving experiences
[7, 15•, 25], attachment insecurity prospectively influences
the capacity for empathic understanding [96]. Without basic
security in early attachment relationships, empathy may be
limited to SR hyper-reactivity, implemented as attunement
for potential social threat. BPD may involve developmental
failure of progression to MSA processing.
Preoccupied and disorganized attachment classifications
are prevalent in BPD [47], along with lower reflective
functioning [27], the focus of both mentalization-based
[23] and transference-focused psychotherapies [24]. Inse-
cure attachment may reflect dysfunctional neuropeptide sig-
naling and empathic network dysregulation. Adverse
influences of development upon empathic processing also
indicate potential for therapeutic neuroplasticity in empathic
networks. Healthy individuals who develop expertise in
alleviating pain eventually increase MSA and inhibit SR
processing while viewing painful stimuli [97]. Training in
emotional reappraisal similarly decreases SR and increases
MSA activity, tempering affective responses [98]. BPD
subjects continue to demonstrate SR hyper-reactivity and
MSA impairment despite such training [19]. Given the
success of psychotherapy in treating BPD [99, 100], foster-
ing mentalization or skills-based learning through psycho-
therapy and the psychotherapeutic relationship may improve
interpersonal functioning by improving adaptive regulation
of empathic networks. The most empirically effective psy-
chotherapeutic interventions in this process remain unclear
for BPD.
Conclusions
Despite severe interpersonal symptoms, empathic dysfunc-
tion is subtle in BPD. Interactions between genetic, neuro-
cognitive, and developmental risk factors may entrain
hyper-reactive SR and impaired MSA networks via abnor-
mal neuropeptide signaling and painful attachment insecu-
rity [45]. Empathic dysfunction may exacerbate BPD
symptoms, especially during perceived social threat. A fo-
cus on attachment and neurobiological functioning is need-
ed for comprehensive understanding of the heterogenous
etiology and psychopathology of BPD. This could provide
earlier clinical identification of BPD and more effective
treatments targeting refractory symptoms [6]. The present
model should be tested with naturalistic neuroimaging para-
digms over the course of BPD and imaging results of ex-
perimental interventions.
Curr Psychiatry Rep (2013) 15:344
The value of this model lies in its potential ability to
explain clinical phenomena associated with BPD, bridging
gaps between theory and empirical research. It may inspire
testable hypotheses for a more comprehensive understand-
ing of BPD. Future neurobiological research will assess the
impact of attachment classification, developmental history,
and genetics on the functional neurobiology of empathic
networks. Ideally, prospective research will distinguish the
respective roles of genetics, trauma, and neurocognitive
dysfunction in contributing to empathic dysfunction. Care-
ful study of empathic network connectivity across the life-
span could assist in predicting BPD or defining prognostic
factors.
Neuroimaging research should include naturalistic para-
digms similar to real-life interpersonal experience, as a
complement to basic, laboratory tasks isolating components
of social cognition [2•, 30]. Empathic dysfunction may only
manifest itself during naturalistic contexts involving salient
social threat. By testing for correlation between epigenetics,
attachment classification, empathic performance, and neural
activity we can understand effects of genes and development
on everyday empathy. An experimental approach, in which
task conditions vary in terms of ambiguity, complexity, or
social threat provocation may be necessary to trigger aber-
rant empathic processing.
Attachment insecurity, intrapsychic pain, and empathic
dysfunction in BPD cause significant distress and disability,
despite advances in evidence-based psychotherapy and psy-
chopharmacology. Integrative, neurodevelopmental re-
search may improve the ability to intervene earlier and
more effectively in the course of BPD. Neurobiological
research on dysregulation of empathic networks shall bring
a more precise understanding of the mechanism via which
BPD psychopathology wreaks havoc in patients’ lives, as-
sist in earlier identification, and lead to more effective
treatments.
Disclosure No potential conflicts of interest relevant to this article
were reported.
References
Papers of particular interest, published recently, have been
highlighted as:
• Of importance
1. Leiberg S, Anders S. The multiple facets of empathy: A survey of
theory and evidence. Prog Brain Res. 2006;156:419–40.
2. • Zaki J, Ochsner K. The neuroscience of empathy: progress,
pitfalls and promise. Nat Neurosci. 2012;15(5):675–80. This re-
view highlights the need for naturalistic empathy research and
summarizes research on SR and MSA processing thus far in
nonclinical subjects.
Curr Psychiatry Rep (2013) 15:344
3. Beebe B, Lachmann FM. Infant research and adult treatment: Co-
constructing interactions. Hillsdale: Analytic Press; 2002.
4. • Decety J, Michalska KJ. Neurodevelopmental changes in the
circuits underlying empathy and sympathy from childhood to
adulthood. Dev Sci. 2010;13:886–99. This study illustrates key
changes in the functioning of empathic circuitry across
development.
5. Fonagy P, Gergely G, Target M. The parent-infant dyad and the
construction of the subjective self. J Child Psychol Psychiatry.
2007;48:288–328.
6. Choi-Kain LW, Zanarini MC, Frankenburg FR, et al. A longitu-
dinal study of the 10-year course of interpersonal features in
borderline personality disorder. J Pers Disord. 2010;24:365–76.
7. Gunderson JG, Lyons-Ruth K. BPD’s interpersonal hypersensi-
tivity phenotype: a gene-environment-developmental model. J
Pers Disord. 2008;22(1):22–41.
8. American Psychiatric Association. Diagnostic and statistical
manual of mental disorders. 4th ed. Washington, DC: American
Psychiatric Association; 2000.
9. Black DW, Blum N, Pfohl B, et al. Suicidal behavior in border-
line personality disorder: prevalence, risk factors, prediction, and
prevention. J Pers Disord. 2004;18:226–39.
10. Brodsky BS, Groves SA, Oquendo MA, et al. Interpersonal
precipitants and suicide attempts in borderline personality disor-
der. Suicide Life Threat Behav. 2006;36(3):313–22.
11. Jovev M, Jackson HJ. The relationship of borderline personality
disorder, life events and functioning in an Australian psychiatric
sample. J Pers Disord. 2006;20(3):205–17.
12. Bender DS, Skodol AE. Borderline personality as a self-other
representational disturbance. J Person Disord. 2007;21:500–17.
13. Fonagy P, Luyten P. A developmental, mentalization-based ap-
proach to the understanding and treatment of borderline person-
ality disorder. Develop Psychopathol. 2009;21:1355–81.
14. Levy KN, Edell WS, McGlashan TH. Depressive experiences in
inpatients with borderline personality disorder. Psychiatr Q.
2007;78:129–43.
15. • Steele H, Siever LJ. An attachment perspective on borderline
personality disorder: Advances in gene-environment considera-
tions. Curr Psychiatry Rep. 2010;12:61–7. This review summarizes
present thinking about gene by environment interactions leading to
insecure attachment and borderline personality disorder.
16. • Dziobek I, Preissler S, Grozdanovic Z, et al. Neuronal correlates
of altered empathy and social cognition in borderline personality
disorder. NeuroImage. 2011;57(2):539–48. This neuroimaging
study comports specifically with the present model of disturban-
ces in empathic processing in BPD. Borderline subjects demon-
strated impairment in MSA regions and hyperactivation of SR
regions in a novel empathy paradigm.
17. • Hazlett EA, Zhang J, New AS, et al. Potentiated amygdala
response to repeated emotional pictures in borderline personality
disorder. Biol Psychiatry. 2012;72(6):448–56. This study illus-
trates amygdala hyper-reactivity and lack of habitation in BPD
subjects in response to evaluation of repeated interpersonal stim-
uli of positive or negative valence (SR hyper-reactivity), along
with blunted subjective appraisal of these stimuli (difficulty with
empathic deliberation).
18. King-Casas B, Sharp C, Lomax-Bream L, et al. The rupture and
repair of cooperation in borderline personality disorder. Science.
2008;321:806–10.
19. Koenigsberg HW, Fan J, Ochsner KN, et al. Neural correlates of
the use of psychological distancing to regulate responses to
negative social cues: A study of patients with borderline person-
ality disorder. Biol Psychiatry. 2009;66:354–863.
20. Mier D, Lis S, Esslinger C, et al. Neuronal correlates of social
cognition in borderline personality disorder. Soc Cogn Affect
Neurosci. 2012 (epub ahead of print)
Page 9 of 11, 344
21. Minzenberg MJ, Fan J, New AS, et al. Fronto-limbic dys-
function in response to facial emotion in borderline person-
ality disorder: An event-related fMRI study. Psychiatry Rese.
2007;155:231–43.
22. New AS, Hazlett EA, Newmark RE, et al. Laboratory induced
aggression: A positron emission tomography study of aggressive
individuals with borderline personality disorder. Biol Psychiatry.
2009;66:1107–14.
23. Bateman AW, Fonagy P. Mentalization-based treatment for bor-
derline personality disorder: A practical guide. Oxford: Oxford
University Press; 2006.
24. Levy KN, Meehan KB, Kelly KM, et al. Change in attachment
patterns and reflective function in a randomized control trial of
transference-focused psychotherapy for borderline personality
disorder. J Consul Clin Psychol. 2006;74:1027–40.
25. Judd PH. Neurocognitive impairment as a moderator in the de-
velopment of borderline personality disorder. Dev Psychopathol.
2005;17(4):1173–96.
26. Ruocco AC, Medaglia JD, Tinker JR, et al. Medial prefrontal
cortex hyperactivation during social exclusion in borderline per-
sonality disorder. Psychiatry Res. 2010;181(3):233–6.
27. Fonagy P, Leigh T, Steele M, et al. The relation of attachment
status, psychiatric classification and response to psychotherapy. J
Consul Clin Psychol. 1996;64:22–31.
28. Hesse E. The Adult Attachment Interview: Protocol, method of
analysis, and empirical studies. In: Hess E, editor. Handbook of
attachment. 2nd ed. New York: Theory, Research, and Clinical
Applications. Guilford Press; 2008. p. 552–98.
29. Eisenberg N. Emotion, regulation, and moral development. Ann
Rev Psychol. 2000;51:665–97.
30. Zaki J, Weber J, Bolger N, et al. The neural bases of empathic
accuracy. Proc Natl Acad Sci. 2009;106:11382–7.
31. Spreng RN, Mar RA, Kim AS. The common neural basis of
autobiographical memory, prospection, navigation, theory of
mind, and the default mode: a quantitative meta-analysis. J
Cogn Neurosci. 2009;21(3):489–510.
32. Legrand D, Ruby P. What is self-specific? Theoretical investiga-
tion and critical review of neuroimaging results. Psychol Rev.
2009;116:252–82.
33. Lieberman MD. Social cognitive neuroscience: A review of core
processes. Ann Rev Psychol. 2007;58:259–89.
34. Tamir DI, Mitchell JP. Neural correlates of anchoring-and-
adjustment during mentalizing. Proc Natl Acad Sci U S A.
2010;107(24):10827–32.
35. Mitchell JP, Schirmer J, Ames DL, Gilbert DT. Medial prefrontal
cortex predicts intertemporal choice. J Cogn Neurosci. 2011;23
(4):857–66.
36. D’Argembeau A, Feyers D, Majerus S, et al. Self-reflection
across time: Cortical midline structures differentiate between
present and past selves. Soc Cog Affect Neurosci. 2008;3:244–
52.
37. Mitchell JP, Macrae CN, Banaji MR. Dissociable medial prefron-
tal contributions to judgments of similar and dissimilar others.
Neuron. 2006;50:661.
38. Powell LJ, Macrae CN, Cloutier J, et al. Dissociable neural
substrates for agentic versus conceptual representations of self.
J Cogn Neurosci. 2010;22(10):2186–97.
39. Otti A, Guendel H, Laer L, et al. I know the pain you feel-how the
human brain’s default mode predicts our resonance to another’s
suffering. Neuroscience. 2010;169:143–8.
40. Zaki J, Hennigan K, Weber J, et al. Social cognitive conflict
resolution: Contributions of domain general and domain specific
neural systems. J Neurosci. 2010;30:8481–8.
41. Minzenberg MJ, Poole JH, Vinogradov S. Social-emotion recog-
nition in borderline personality disorder. Compr Psychiatry.
2006;47:468–74.
344, Page 10 of 11
42. Stillman TF, Baumeister RF, Lambert NM, et al. Alone and
without purpose: Life loses meaning following social exclusion.
J Exp Soc Psychol. 2009;45:686–94.
43. Baumeister RF, Twenge JM, Nuss CK. Effects of social exclusion
on cognitive processes: Anticipated aloneness reduces intelligent
thought. J Pers Soc Psychol. 2002;83:817–27.
44. Cacioppo JT, Norris CJ, Decety J. In the eye of the beholder:
Individual differences in perceived social isolation predict regional
brain activation to social stimuli. J Cogn Neurosci. 2009;21:83–92.
45. Stanley B, Siever LJ. The interpersonal dimension of borderline
personality disorder: Toward a neuropeptide model. Am J
Psychiatry. 2010;167:24–39.
46. Prossin AR, Love TM, Koeppe RA, et al. Dysregulation of
regional endogenous opioid function in borderline personality
disorder. Am J Psychiatry. 2010;167:925–33.
47. Agrawal HR, Gunderson J, Holmes BM, Lyons-Ruth K.
Attachment studies with borderline patients: a review. Harv Rev
Psychiatry. 2004;12(2):94–104.
48. Lemche E, Giampietro VP, Surguladze SA, et al. Human attach-
ment security is mediated by the amygdala: evidence from com-
bined fMRI and psychophysiological measures. Hum Brain
Mapp. 2006;27(8):623–35.
49. Suslow T, Kugel H, Rauch AV, et al. Attachment avoidance
modulates neural response to masked facial emotion. Hum
Brain Mapp. 2009;30(11):3553–62.
50. Vrticka P, Andersson F, Grandjean D, et al. Individual attachment
style modulates human amygdala and striatum activation during
social appraisal. PLoS One. 2008;3(8):e2868.
51. Harari H, Shamay-Tsoory SG, Ravid M, et al. Double dissocia-
tion between cognitive and affective empathy in borderline per-
sonality disorder. Psychiatry Res. 2010;175:277–9.
52. Preissler S, Dziobek I, Ritter K, et al. Social cognition in border-
line personality disorder: Evidence for disturbed recognition of
the emotions, thoughts, and intentions of others. Front Behav
Neurosci. 2010;4:1–8.
53. • Daros AR, Zakzanis KK, Ruocco AC. Facial emotion recogni-
tion in borderline personality disorder. Psychol Med. 2012 (epub
ahead of print). This meta-analysis highlights and summarizes
facial emotion recognition findings in BPD, demonstrating dis-
tinct difficulties for BPD subjects during processing of ambigu-
ous or socially threatening stimuli.
54. Fertuck EA, Jekal A, Song I, et al. Enhanced ‘Reading the Mind
in the Eyes’ in borderline personality disorder compared to
healthy controls. Psychol Medicine. 2009;39(12):1979–88.
55. Lynch TR, Rosenthal MZ, Kosson DS, et al. Heightened sensi-
tivity to facial expressions of emotion in borderline personality
disorder. Emotion. 2006;6:647–55.
56. Arntz A, Bernstein D, Oorschot M, Schobre P. Theory of mind in
borderline and cluster-C personality disorder. J Nerv Ment Dis.
2009;197(11):801–7.
57. Ruocco AC, Amirthavasagam S, Choi-Kain LW, McMain SF.
Neural correlates of negative emotionality in borderline person-
ality disorder: an activation-likelihood-estimation meta-analysis.
Biol Psychiatry. 2012 (epub ahead of print).
58. Romero-Canyas R, Downey G, Berenson K, et al. Rejection
sensitivity and the rejection-hostility link in romantic relation-
ships. J Person. 2010;78:119–48.
59. Ayduk O, Zayas V, Downey G, et al. Rejection sensitivity and
executive control: joint predictors of borderline personality fea-
tures. J Res Person. 2008;42:151–68.
60. Berenson KR, Gyurak A, Ayduk O, et al. Rejection sensitivity
and disruption of attention by social threat cues. J Res Person.
2009;43:1064–72.
61. Pickett CL, Gardner WL, Knowles M. Getting a cue: The need to
belong and enhanced sensitivity to social cues. Pers Soc Psychol
Bull. 2004;30:1095–107.
Curr Psychiatry Rep (2013) 15:344
62. Babcock JC, Jacobson N, Gottman J, Yerington TP. Attachment,
emotional regulation, and the function of marital violence: differ-
ences between secure, preoccupied, and dismissing violent and
non-violent husbands. J Family Violence. 2000;15:391–409.
63. Barnow S, Stopsack M, Grabe HJ, et al. Interpersonal evaluation
bias in borderline personality disorder. Behav Res Ther.
2009;47:359–65.
64. Stern MI, Herron WG, Primavera LH, et al. Interpersonal per-
ceptions of depressed and borderline inpatients. J Clin Psychol.
1997;53:41–9.
65. Westen D, Lohr N, Silk KR, et al. Object relations and social
cognition in borderlines, major depressives, and normals: A the-
matic apperception test analysis. J Consul Clin Psychol.
1990;2:355–64.
66. Domes G, Czieschnek D, Weidler F, et al. Recognition of facial
affect in borderline personality disorder. J Pers Disord.
2008;22:135–47.
67. von Ceumern-Lindenstjerna IA, Brunner R, Parzer P, et al. Initial
orienting to emotional faces in female adolescents with borderline
personality disorder. Psychopathology. 2010;43(2):79–87.
68. Staebler K, Renneberg B, Stopsack M, et al. Facial emotion
expression in reaction to social exclusion in borderline personal-
ity disorder. Psychol Med. 2011;9:1–10.
69. Holm AL, Severinsson E. The emotional pain and distress of
borderline personality disorder: A review of the literature. Int J
Mental Health Nurs. 2008;17:27–35.
70. Rusch N, Lieb K, Gottler I, et al. Shame and implicit self-concept
in women with borderline personality disorder. Am J Psychiatry.
2007;164:500–8.
71. Stiglmayr CE, Ebner-Priemer UW, Bretz J, et al. Dissociative
symptoms are positively related to stress in borderline personality
disorder. Acta Psychiatr Scand. 2008;117:139–47.
72. New AS, Rot MA, Ripoll LH, et al. Empathy and alexithymia in
borderline personality disorder: clinical and laboratory measures.
J Pers Disord. 2012;26(5):660–75.
73. Franzen N, Hagenhoff M, Baer N, et al. Superior ‘theory of mind’
in borderline personality disorder: An analysis of interaction
behavior in a virtual trust game. Psychiatry Res. 2010;187(1–
2):224–33.
74. Bartels A, Zeki S. The neural correlates of maternal and romantic
love. NeuroImage. 2004;21:1155–66.
75. Cheng Y, Chen C, Lin CP, et al. Love hurts: An fMRI study.
NeuroImage. 2010;51:923–9.
76. Bartz JA, Zaki J, Bolger N, Ochsner KN. Social effects of
oxytocin in humans: Context and person matter. Trend Cogn
Sci. 2011;15(7):301–9.
77. Depue RA, Morrone-Strupinsky JV. A neurobehavioral model of
affiliative bonding: Implications for conceptualizing a human trait
of affiliation. Behav Brain Sci. 2005;28:313–95.
78. Niedtfeld I, Schulze L, Kirsch P, et al. Affect regulation and pain
in borderline personality disorder: A possible link to the under-
standing of self-injury. Biol Psychiatry. 2010;68:383–91.
79. Nock MK. Why do People hurt themselves? New insights into
the nature and functions of self-injury. Curr Dir Psychol Sci.
2009;18(2):78–83.
80. Neumann ID. Brain oxytocin: A key regulator of emotional and
social behaviors in both females and males. J Neuroendocrinol.
2008;20:858–65.
81. De-Dreu CKW, Greer LL, Handgraaf MJJ, et al. The neuropep-
tide oxytocin regulates parochial altruism in intergroup conflict
among humans. Science. 2010;328:1408–11.
82. De-Dreu CKW, Greer LL, van Kleef GA, et al. Oxytocin
promotes human ethnocentrism. Proc Natl Acad Sci.
2011;108:1262–6.
83. Mobbs D, Yu R, Meyer M, et al. A key role for similarity in
vicarious reward. Science. 2009;324:900.
Curr Psychiatry Rep (2013) 15:344
84. Bartz JA, Zaki J, Bolger N, et al. Oxytocin selectively improves
empathic accuracy. Psychol Sci. 2010;21:1426–8.
85. Bartz JA, Zaki J, Ochsner KN, et al. Effects of oxytocin on
recollections of maternal care and closeness. Proc Natl Acad
Sci. 2010;107:21371–5.
86. Bakermans-Kranenburg MJ, van-Ijzendoorn MH, Riem MM, et
al. Oxytocin decreases handgrip force in reaction to infant crying
in females without harsh parenting experiences. Soc Cogn Affect
Neurosci. 2012 (epub ahead of print)
87. van-Ijzendoorn MH, Huffmeijer R, Alink LR, et al. The impact of
oxytocin administration on charitable donating is moderated by
experiences of parental love-withdrawal. Front Psychol. 2011
(epub ahead of print).
88. Simeon D, Bartz J, Hamilton H, et al. Oxytocin administration
attenuates stress reactivity in borderline personality disorder: A
pilot study. Psychoneuroendocrinology. 2011;36(9):1418–21.
89. Bartz J, Simeon D, Hamilton H, et al. Oxytocin can hinder trust
and cooperation in borderline personality disorder. Soc Cogn
Affect Neurosci. 2010 (epub ahead of print).
90. Reid VM, Striano T, Iacoboni M. Neural correlates of dyadic
interaction during infancy. Dev Cogn Neurosci. 2011;1(2):124–30.
91. Brass M, Schmitt RM, Spengler S, et al. Investigating action
understanding: Inferential processes versus action simulation.
Curr Biol. 2007;17:2117–21.
92. Decety J, Moriguchi Y. The empathic brain and its dysfunc-
tion in psychiatric populations: Implications for intervention
Page 11 of 11, 344
across different clinical conditions. Biopsychosoc Med.
2007;1:22–65.
93. Decety J, Michalska KJ, Akitsuki Y. Who caused the pain? A
functional MRI investigation of empathy and intentionality in
children. Neuropsychologia. 2008;46:2607–14.
94. Rothbart MK, Ahadi SA, Hershey KL. Temperament and social
behavior in childhood. Merrill-Palmer Quarterly. 1994;40:21–39.
95. Moriguchi Y, Ohnishi T, Mori T, et al. Changes of brain activity
in the neural substrates for theory of mind during childhood and
adolescence. Psychiatry Clin Neurosci. 2007;61:355–63.
96. Steele H, Steele M, Croft C. Early attachment predicts emotion
recognition at 6 and 11 years old. Attach Hum Develop.
2008;10:379–93.
97. Cheng Y, Lin CP, Liu HL, et al. Expertise modulates the percep-
tion of pain in others. Curr Biol. 2007;17:1708–13.
98. Koenigsberg HW, Fan J, Ochsner KN, et al. Neural correlates of
using distancing to regulate emotional responses to social situa-
tions. Neuropsychologia. 2010;48:1813–22.
99. Bateman A, Fonagy P. Randomized controlled trial of outpatient
mentalization-based treatment versus structured clinical manage-
ment for borderline personality disorder. Am J Psychiatry.
2009;166(12):1355–64.
100. Levy KN, Meehan KB, Kelly KM, et al. Change in attachment
patterns and reflective function in a randomized control trial of
transference-focused psychotherapy for borderline personality
disorder. J Consult Clin Psychol. 2006;74(6):1027–40.