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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
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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
Abstract

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.

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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.

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