Trial document

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Trial Description

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Hypersensitivity to social threat, anger, and (auto)aggression in BPD

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Trial Acronym


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URL of the Trial


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Brief Summary in Lay Language

Patients with borderline personality disorder (BPD) often feel threatened or rejected by other people which results in frequent feelings of anger. There is some evidence that this enhanced sensitivity for interpersonal threats, the increased feelings of anger as well as aggressive and self-injurous behavior in BPD may be due to problems in cognitions about others and in the processing of emotions. Previous research has shown that this is particularly related to differences in the activity of the limbic system, a part of the brain which is crucially involved in the processing of emotions. Although BPD is almost equally distributed among genders, gender and age differences could have a strong impact on the processing of social threat, anger, and aggression.
The present project therefore investigates differences in the activation of brain regions between patients with BPD and healthy control participants in response to interpersonal threat. In addition, we will regard differences in behavioral tendencies triggered by interpersonal threat. Hence, 85 male and female patients with BPD, 35 female patients with remitted BPD, 35 female patients with posttraumatic stress disorder (PTSD), and 85 healthy male and female control participants will be exposed to emotional faces and situations. Patients between 15 and 40 years will be included in order to investigate age effects.

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Brief Summary in Scientific Language

Patients with borderline personality disorder (BPD) show a hypersensitivity to experience interpersonal threat, tend to ascribe resentment to others, and consequently frequently experience anger that they may not be able to control. Impaired social cognitive functions such as a bias towards the perception of anger in facial emotion recognition may contribute to anger proneness.
The project deals with behavioral and neural correlates of BPD patients’ (i) hypersensitivity to social threat and its implications on action dispositions in terms of approach or avoidance, and (ii) experience of anger as a prominent affect and related behavioral manifestations of aggression and autoaggression. In an additional exploratory approach, effects of gender and age will be systematically considered for the first time in research on emotional processes in BPD. We have planned three studies: 1. In a behavioral experiment we will investigate the processing of ambiguous bimodal stimuli. 2. In a fMRI study we aim to study behavioral approach and avoidance tendencies in response to emotional facial expressions as well as the underlying brain circuits involving the prefronto-amygdalar connectivity, the ventral striatum, the insular cortex and different parts of the anterior cingulate cortex. 3. In a second fMRI study using script-driven imagery, we will investigate psychophysiological reactivity in response to an anger induction paradigm followed by the imagination of aggressive vs. autoaggressive behavior, again with the focus on prefronto-amygdalar dysfunction. Male and female BPD patients (N=85) will be compared to healthy controls (N=85) and a clinical control group of female patients with posttraumatic stress disorder (but without BPD; N=35). In addition, a group of female patients with remitted BPD (N=35) will be investigated.

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Organizational Data

  •   DRKS00003282
  •   2011/10/18
  •   [---]*
  •   yes
  •   Approved
  •   S-072/2011, Ethik-Kommission I der Medizinischen Fakultät Heidelberg
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   F60.31 -  [generalization F60.3: Emotionally unstable personality disorder]
  •   F43.1 -  Post-traumatic stress disorder
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Interventions/Observational Groups

  •   All patients(N=50 female BPD patients, age: 15-40 years and N=35 male BPD patients, age: 18-40 years) participate at 3 occasions consisting of an extensive clinical diagnostic (occasion 1, duration: about 2.5 h), a behavioral study (occasion 2, duration: about 0.5 h), and a magnet resonance imaging (MRI) measurement (occasion 3, duration: 1.5 h, 1 h in the MRI). At this third occasion 2 functional magnet resonance imaging (fMRI) experiments and a structural MRI as well as a DTI measurement will take place. In addition, all patients fill in several psychometric questionnaires (duration: about 1 h) and collect 16 salivary samples for testosterone and cortisol measurements. The whole study has a duration of about 5.5 h.
    Occasion 1 - Patient information and clinical assessment:
    Prior to the experiment, all patients receive extensive written and oral information about the course and content of the study. In addition, all patients undergo a thorough clincial diagnostic assessment regarding borderline personality disorder and other personality disorders (DSM-IV criteria) with a structured clinicial interview International Personality Disorder Examination (Loranger et al., 1994). PTSD and axis I comorbidities are assessed with SKID-I interviews. Clinical symptoms are additionally assessed with the Borderline Symptom Checklist (Bohus et al., 2001), the Zanarini Rating Scale for BPD (Zanarini et al., 2003), the Beck Depression Inventory (Beck et al., 1995), the State-Trait Anxiety Inventory (Laux et al., 1981), the Symptom Chekclist (Franke, 1995), The Emotion Regulation Scale (Gratz & Roemer, 2004), the Childhood Trauma Questionnaire (Bernstein & Fink, 1998), the Aggression Questionnaire (Heubrock & Petermann, 2008), the State-Trait Anger Expression Inventory (Spielberger, 1991), and the Barrett Impulsivity Questionnaire (Patton et al., 1995).
    Occasion 2 - Behavioral experiment:
    Subjects will be presented faces of the “Pictures of Facial Affect” (Ekman & Friesen, 1976) with emotional expressions ranging from happy to angry expressions in 10% steps (de Gelder & Vroomen, 2000; Domes et al., 2008). At the same time, neutral sentences will be presented in either a happy or angry intonation resulting in a forced-choice bimodal emotion identification task, in which participants will be asked to choose as quickly as possible which particular emotion the face displays.
    Occasion 3 - MRI measurement:
    fMRI experiment 1 - Approach-Avoidance task:
    The subjects will be presented slides of angry and happy faces from the “Pictures of Facial Affect” (Ekman & Friesen, 1976). The Approach–Avoidance task (AA task) will involve an affect-congruent and an affect-incongruent response condition (Perlis et al., 2008; Roelofs et al., 2009). Participants will be explicitly instructed to categorize the facial expressions and to respond as accurately and quickly as possible. In the affect-congruent condition of the AA task, participants will be instructed to pull the joystick towards their body in response to a happy face and to push the joystick away in response to an angry face. In the incongruent condition, the instructions will be reversed (i.e. angry–pull; happy–push).
    fMRI experiment 2 - script-driven anger induction and imagination of (auto-)aggressive behavior:
    Two standard scripts describing the circumstances and the execution of an act of (auto)aggressive behavior will be developed in first person singular, comprising the following four sections: neutral sequence (baseline), trigger situation (anger induction), (auto) aggressive behavior, and relaxation (Dougherty et al., 2004; Kraus et al., 2010). At the beginning of the experiment, participants will be instructed to imagine the description in the script as vividly as possible and to imagine all the feelings and sensations while listening to the script. Before and after each of the scripts, participants will be asked to rate the vividness of their imagery, their aversive inner tension, dissociation, and their feelings of anger as well as negative and positive emotions. During the whole experiment, skin conductance levels, heart rates, electromyography, and forehead temperature will be measured.
    Magnetic resonance imaging:
    Diffusion and T1 weighted whole brain images and blood-oxygenation-level-dependent (BOLD) functional T2*-images (fMRI) will be acquired on a 3 Tesla whole body MR scanner (Trio; Siemens) equipped with a head coil. Total duration: 60 min.
  •   Healthy (N=50 women and N=35 men) and clinical control group (N=35 female PTSD and N=35 female remitted BPD patients); experimental setup and course is identical for all patients and participants; see arm 1.
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  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   [---]*
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Primary Outcome

Experiment 1 (Behavioral study): Bias for anger in complex bimodal stimuli, comparison of BPD patients and healthy controls, and PTSD patients, measure: behavioral data.
Experiment 2 (fMRI 1): A. Approach and avoidance tendencies for happy and angry faces, comparison of BPD patients and healthy controls, and PTSD patients, measure: reaction time data; B. activiations in the limbic system and prefrontal-amygdalar connectivity, comparison of BPD patients and healthy controls, and PTSD patients, measure: fMRI data; C. correlations between aggressiveness and gender with approach tendencies for angry faces, comparison of male and female BPD patients and male and female healthy controls, measures: reaction time data, aggressiveness questionnaire scores, fMRI data.
Experiment 3 (fMRI 2): A. Strength of feelings of anger during imagination of aggressive and autoaggressive scripts, comparison of BPD patients and healthy controls, and PTSD patients, measures: subjective arousal ratings, fMRI, autonomic measures; B. activiations in the limbic system and prefrontal-amygdalar connetivity during anger induction, comparison of BPD patients and healthy controls, and PTSD patients, measure: fMRI.

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Secondary Outcome

Not given

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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  •   Actual
  •   2012/05/14
  •   240
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   15   Years
  •   40   Years
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Additional Inclusion Criteria

General inclusion criteria: age of 15-40 years, readiness for participation. Additional inclusion criterium for boderline patients: Boderline personality disorder (DSM-IV). Additional inclusion criterium for PTBS-controls: posttraumatic stress disorder (DSM-IV)

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Exclusion Criteria

General exclusion criteria: pregnancy, lifetime-diagnosis of schizophrenic disorder, bipolar-I-disorder, substance abuse within the last year. organic head injury, severe non-surgical or neurological brain disorder, craniocerebral injury, metallic residue, claustrophobia.
Additional exclusion criteria for PTBS-controls: more than 1 DSM-IV criterium for BPD. Additional exclusion criteria for healthy controls: more than one DSM-IV criterium for BPD, any psychiatric disorder.

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Sources of Monetary or Material Support

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    • Deutsche Forschungsgemeinschaft
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
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  •   Recruiting complete, follow-up complete
  •   2015/08/31
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Trial Publications, Results and other Documents

  •   Izurieta Hidalgo, N. A., Oelkers-Ax, R., Nagy, K., Mancke, F., Bohus, M., Herpertz, S. C., & Bertsch, K. (2016). Time course of facial emotion processing in women with borderline personality disorder – an ERP study. Journal of Psychiatry and Neuroscience, 41, 16–26.
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