Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

Articles   |    
Oxytocin and Reduction of Social Threat Hypersensitivity in Women With Borderline Personality Disorder
Katja Bertsch, Ph.D.; Matthias Gamer, Ph.D.; Brigitte Schmidt, M.D.; Ilinca Schmidinger, M.D.; Stephan Walther, Ph.D.; Thorsten Kästel, M.S.; Knut Schnell, M.D.; Christian Büchel, M.D.; Gregor Domes, Ph.D.; Sabine C. Herpertz, M.D.
Am J Psychiatry 2013;170:1169-1177. doi:10.1176/appi.ajp.2013.13020263
View Author and Article Information

The authors report no financial relationships with commercial interests.

Funded by a grant of the German Federal Ministry for Education and Research (to Dr. Herpertz) (Network “Social Cognition,” 01GW0784)

From the Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Neuroradiology, University of Heidelberg; Department of Psychology, Laboratory for Biological and Personality Psychology, University of Freiburg, Freiburg, Germany; and Freiburg Brain Imaging, University Medical Center, University of Freiburg.

Address correspondence to Dr. Bertsch (katja.bertsch@med.uni-heidelberg.de).

Copyright © 2013 by the American Psychiatric Association

Received February 25, 2013; Revised April 12, 2013; Accepted May 06, 2013.

An erratum to this article has been published | view the erratum

Objective  Patients with borderline personality disorder are characterized by emotional hyperarousal with increased stress levels, anger proneness, and hostile, impulsive behaviors. They tend to ascribe anger to ambiguous facial expressions and exhibit enhanced and prolonged reactions in response to threatening social cues, associated with enhanced and prolonged amygdala responses. Because the intranasal administration of the neuropeptide oxytocin has been shown to improve facial recognition and to shift attention away from negative social information, the authors investigated whether borderline patients would benefit from oxytocin administration.

Method  In a randomized placebo-controlled double-blind group design, 40 nonmedicated, adult female patients with a current DSM-IV diagnosis of borderline personality disorder (two patients were excluded based on hormonal analyses) and 41 healthy women, matched on age, education, and IQ, took part in an emotion classification task 45 minutes after intranasal administration of 26 IU of oxytocin or placebo. Dependent variables were latencies and number or initial reflexive eye movements measured by eye tracking, manual response latencies, and blood-oxygen-level-dependent responses of the amygdala to angry and fearful compared with happy facial expressions.

Results  Borderline patients exhibited more and faster initial fixation changes to the eyes of angry faces combined with increased amygdala activation in response to angry faces compared with the control group. These abnormal behavioral and neural patterns were normalized after oxytocin administration.

Conclusions  Borderline patients exhibit a hypersensitivity to social threat in early, reflexive stages of information processing. Oxytocin may decrease social threat hypersensitivity and thus reduce anger and aggressive behavior in borderline personality disorder or other psychiatric disorders with enhanced threat-driven reactive aggression.

Abstract Teaser
Figures in this Article

Your Session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 1. Response Latencies in Borderline Patients and Healthy Control Subjects in the Oxytocin and Placebo Conditions as a Function of Facial Expression (Angry, Fearful, Happy) and Initial Fixation (Eyes, Mouth)a

a Error bars indicate standard error of the mean.

** p<0.01.

FIGURE 2. Proportion of Fixation Changes Targeting the Other Major Facial Feature After Stimulus Offset in Borderline Patients and Healthy Control Subjects in the Oxytocin and Placebo Conditions as a Function of Facial Expression (Angry, Fearful, Happy)a

a Error bars indicate standard error of the mean.

* p<0.05.

FIGURE 3. Latency of Fixation Changes Targeting the Other Major Facial Feature After Stimulus Offset in Patients With Borderline Personality Disorder and Healthy Control Subjects in the Oxytocin and Placebo Conditions as a Function of Facial Expression (Angry, Fearful, Happy)a

a Error bars indicate standard error of the mean.

* p<0.05. ** p<0.01.

FIGURE 4. Amygdala Activation in Response to Emotional Expressiona

a Panel A presents the amygdala region showing a significant interaction of condition (oxytocin, placebo) and emotional expression (angry, happy) in borderline patients (left). A statistical map (coronal plane) of the interaction effect revealing a cluster in the right amygdala (peak voxel [x, y, z]: 32, −6, −14) is also shown. The statistical map is overlaid on a single-subject canonical brain image with a display threshold of p<0.01, uncorrected. Contrast estimates of this cluster (right) are presented, with error bars representing the standard error of the mean. The interaction of group (borderline, control), condition (oxytocin, placebo), and emotional expression (angry, happy) was marginally significant (peak voxel [x, y, z]: 32, −6, −14; z=3.15 p=0.09, family-wise-error corrected). In panel B, the scatterplot depicts the correlation of amygdala activation for angry faces with initial fixation on the mouth in the peak voxel (x, y, z: 32, −6, −14) and latency of fixation changes toward the eye region of angry faces separately for borderline patients (R2=0.16) and healthy control participants (R2=0.04).

Anchor for Jump
TABLE 1.Demographic and Clinical Characteristics of Borderline Patients and Healthy Control Subjectsa
Table Footer Note

a Two borderline patients from the original patient sample (N=40) had to be excluded because their hormonal levels exceeded values of the early follicular phase (progesterone level <2.0 ng/ml; estradiol level <165 pg/ml).

Table Footer Note

b Data indicate comparison of borderline patients with healthy control subjects.



Lieb  KP;  Zanarini  MC;  Schmahl  C;  Linehan  MM;  Bohus  M:  Borderline personality disorder.  Lancet 2004; 364:453–461
[CrossRef] | [PubMed]
Arntz  A;  Veen  G:  Evaluations of others by borderline patients.  J Nerv Ment Dis 2001; 189:513–521
[CrossRef] | [PubMed]
von Ceumern-Lindenstjerna  IA;  Brunner  R;  Parzer  P;  Mundt  C;  Fiedler  P;  Resch  F:  Initial orienting to emotional faces in female adolescents with borderline personality disorder.  Psychopathology 2010; 43:79–87
[CrossRef] | [PubMed]
von Ceumern-Lindenstjerna  IA;  Brunner  R;  Parzer  P;  Mundt  C;  Fiedler  P;  Resch  F:  Attentional bias in later stages of emotional information processing in female adolescents with borderline personality disorder.  Psychopathology 2010; 43:25–32
[CrossRef] | [PubMed]
Barnow  S;  Stopsack  M;  Grabe  HJ;  Meinke  C;  Spitzer  C;  Kronmüller  K;  Sieswerda  S:  Interpersonal evaluation bias in borderline personality disorder.  Behav Res Ther 2009; 47:359–365
[CrossRef] | [PubMed]
Domes  G;  Czieschnek  D;  Weidler  F;  Berger  C;  Fast  K;  Herpertz  SC:  Recognition of facial affect in borderline personality disorder.  J Pers Disord 2008; 22:135–147
[CrossRef] | [PubMed]
Hazlett  EA;  Zhang  J;  New  AS;  Zelmanova  Y;  Goldstein  KE;  Haznedar  MM;  Meyerson  D;  Goodman  M;  Siever  LJ;  Chu  KW:  Potentiated amygdala response to repeated emotional pictures in borderline personality disorder.  Biol Psychiatry 2012; 72:448–456
[CrossRef] | [PubMed]
Herpertz  SC;  Dietrich  TM;  Wenning  B;  Krings  T;  Erberich  SG;  Willmes  K;  Thron  A;  Sass  H:  Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study.  Biol Psychiatry 2001; 50:292–298
[CrossRef] | [PubMed]
Minzenberg  MJ;  Fan  J;  New  AS;  Tang  CY;  Siever  LJ:  Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study.  Psychiatry Res 2007; 155:231–243
[CrossRef] | [PubMed]
Gamer  M;  Büchel  C:  Amygdala activation predicts gaze toward fearful eyes.  J Neurosci 2009; 29:9123–9126
[CrossRef] | [PubMed]
Kliemann  D;  Dziobek  I;  Hatri  A;  Steimke  R;  Heekeren  HR:  Atypical reflexive gaze patterns on emotional faces in autism spectrum disorders.  J Neurosci 2010; 30:12281–12287
[CrossRef] | [PubMed]
Kliemann  D;  Dziobek  I;  Hatri  A;  Baudewig  J;  Heekeren  HR:  The role of the amygdala in atypical gaze on emotional face in autism spectrum disorders.  J Neurosci 2012; 32:9469–9476
[CrossRef] | [PubMed]
Gamer  M;  Zurowski  B;  Büchel  C:  Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans.  Proc Natl Acad Sci USA 2010; 107:9400–9405
[CrossRef] | [PubMed]
Smith  ML;  Cottrell  GW;  Gosselin  F;  Schyns  PG:  Transmitting and decoding facial expressions.  Psychol Sci 2005; 16:184–189
[CrossRef] | [PubMed]
Heinrichs  M;  Baumgartner  T;  Kirschbaum  C;  Ehlert  U:  Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress.  Biol Psychiatry 2003; 54:1389–1398
[CrossRef] | [PubMed]
Domes  G;  Heinrichs  M;  Michel  A;  Berger  C;  Herpertz  SC:  Oxytocin improves “mind-reading” in humans.  Biol Psychiatry 2007; 61:731–733
[CrossRef] | [PubMed]
Leknes  S;  Wessberg  J;  Ellingsen  DM;  Chelnokova  O;  Olausson  H;  Laeng  B:  Oxytocin enhances pupil dilation and sensitivity to “hidden” emotional expressions.  Soc Cogn Affect Neurosci  (Epub ahead of print, June 29, 2012)
Lischke  A;  Berger  C;  Prehn  K;  Heinrichs  M;  Herpertz  SC;  Domes  G:  Intranasal oxytocin enhances emotion recognition from dynamic facial expressions and leaves eye-gaze unaffected.  Psychoneuroendocrinology 2012; 37:475–481
[CrossRef] | [PubMed]
Schulze  L;  Lischke  A;  Greif  J;  Herpertz  SC;  Heinrichs  M;  Domes  G:  Oxytocin increases recognition of masked emotional faces.  Psychoneuroendocrinology 2011; 36:1378–1382
[CrossRef] | [PubMed]
Domes  G;  Sibold  M;  Schulze  L;  Lischke  A;  Herpertz  SC;  Heinrichs  M:  Intranasal oxytocin increases covert attention to positive social cues.  Psychol Med 2012; 12:1–7.
Ellenbogen  MA;  Linnen  AM;  Grumet  R;  Cardoso  C;  Joober  R:  The acute effects of intranasal oxytocin on automatic and effortful attentional shifting to emotional faces.  Psychophysiology 2012; 49:128–137
[CrossRef] | [PubMed]
Hirosawa  T;  Kikuchi  M;  Higashida  H;  Okumura  E;  Ueno  S;  Shitamichi  K;  Yoshimura  Y;  Munesue  T;  Tsubokawa  T;  Haruta  Y;  Nakatani  H;  Hashimoto  T;  Minabe  Y:  Oxytocin attenuates feelings of hostility depending on emotional context and individuals’ characteristics  Sci Rep2012; 2:384
Bartz  JA;  Zaki  J;  Bolger  N;  Ochsner  KN:  Social effects of oxytocin in humans: context and person matter.  Trends Cogn Sci 2011; 15:301–309
Knobloch  HS;  Charlet  A;  Hoffmann  LC;  Eliava  M;  Khrulev  S;  Cetin  AH;  Osten  P;  Schwarz  MK;  Seeburg  PH;  Stoop  R;  Grinevich  V:  Evoked axonal oxytocin release in the central amygdala attenuates fear response.  Neuron 2012; 73:553–566
[CrossRef] | [PubMed]
Domes  G;  Heinrichs  M;  Gläscher  J;  Büchel  C;  Braus  DF;  Herpertz  SC:  Oxytocin attenuates amygdala responses to emotional faces regardless of valence.  Biol Psychiatry 2007; 62:1187–1190
[CrossRef] | [PubMed]
Kirsch  P;  Esslinger  C;  Chen  Q;  Mier  D;  Lis  S;  Siddhanti  S;  Gruppe  H;  Mattay  VS;  Gallhofer  B;  Meyer-Lindenberg  A:  Oxytocin modulates neural circuitry for social cognition and fear in humans.  J Neurosci 2005; 25:11489–11493
[CrossRef] | [PubMed]
Domes  G;  Lischke  A;  Berger  C;  Grossmann  A;  Hauenstein  K;  Heinrichs  M;  Herpertz  SC:  Effects of intranasal oxytocin on emotional face processing in women.  Psychoneuroendocrinology 2010; 35:83–93
[CrossRef] | [PubMed]
Lischke  A;  Gamer  M;  Berger  C;  Grossmann  A;  Hauenstein  K;  Heinrichs  M;  Herpertz  SC;  Domes  G:  Oxytocin increases amygdala reactivity to threatening scenes in females.  Psychoneuroendocrinology 2012; 37:1431–1438
[CrossRef] | [PubMed]
Meyer-Lindenberg  A;  Domes  G;  Kirsch  P;  Heinrichs  M:  Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine.  Nat Rev Neurosci 2011; 12:524–538
[CrossRef] | [PubMed]
Simeon  D;  Bartz  J;  Hamilton  H;  Crystal  S;  Braun  A;  Ketay  S;  Hollander  E:  Oxytocin administration attenuates stress reactivity in borderline personality disorder: a pilot study.  Psychoneuroendocrinology 2011; 36:1418–1421
[CrossRef] | [PubMed]
Bartz  J;  Simeon  D;  Hamilton  H;  Kim  S;  Crystal  S;  Braun  A;  Vicens  V;  Hollander  E:  Oxytocin can hinder trust and cooperation in borderline personality disorder.  Soc Cogn Affect Neurosci 2011; 6:556–563
[CrossRef] | [PubMed]
Loranger  AW;  Sartorius  N;  Andreoli  A;  Berger  P;  Buchheim  P;  Channabasavanna  SM;  Coid  B;  Dahl  A;  Diekstra  RF;  Ferguson  B  et al:  The International Personality Disorder Examination: the World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration international pilot study of personality disorders.  Arch Gen Psychiatry 1994; 51:215–224
[CrossRef] | [PubMed]
Bohus  M;  Limberger  M;  Frank  U;  Chapman  AL;  Kühler  T;  Stieglitz  RD:  Psychometric properties of the Borderline Symptom List (BSL).  Psychopathology 2007; 40:126–132
[CrossRef] | [PubMed]
Born  J;  Lange  T;  Kern  W;  McGregor  GP;  Bickel  U;  Fehm  HL:  Sniffing neuropeptides: a transnasal approach to the human brain.  Nat Neurosci 2002; 5:514–516
[CrossRef] | [PubMed]
Tzourio-Mazoyer  N;  Landeau  B;  Papathanassiou  D;  Crivello  F;  Etard  O;  Delcroix  N;  Mazoyer  B;  Joliot  M:  Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.  Neuroimage 2002; 15:273–289
[CrossRef] | [PubMed]
Mai  JK;  Assheuer  J;  Paxinos  G:  Atlas of the Human Brain .  San Diego,  Academic, 1997
Daros  AR;  Zakzanis  KK;  Ruocco  AC:  Facial emotion recognition in borderline personality disorder.  Psychol Med 2012; 13:1–11
Adolphs  R:  What does the amygdala contribute to social cognition? Ann N Y Acad Sci 2010; 1191:42–61
[CrossRef] | [PubMed]
Andari  E;  Duhamel  JR;  Zalla  T;  Herbrecht  E;  Leboyer  M;  Sirigu  A:  Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.  Proc Natl Acad Sci USA 2010; 107:4389–4394
[CrossRef] | [PubMed]
Domes  G;  Heinrichs  M;  Kumbier  E;  Grossmann  A;  Hauenstein  KH;  Herpertz  SC:  Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder.  Biol Psychiatry 2013; 74:164–171
[CrossRef] | [PubMed]
Bertsch  K;  Schmidinger  I;  Neumann  ID;  Herpertz  SC:  Reduced plasma oxytocin levels in female patients with borderline personality disorder.  Horm Behav 2013; 63:424–429
[CrossRef] | [PubMed]
Zanarini  MC;  Frankenburg  FR;  Hennen  J;  Reich  DB;  Silk  KR:  Axis I comorbidity in patients with borderline personality disorder: 6-year follow-up and prediction of time to remission.  Am J Psychiatry 2004; 161:2108–2114
[CrossRef] | [PubMed]
References Container

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe

Web of Science® Times Cited: 4

Related Content
See Also...
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 51.  >
DSM-5™ Clinical Cases > Chapter 18.  >
Textbook of Psychotherapeutic Treatments > Chapter 29.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 53.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 45.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles