Edited by: Nelly Alia-Klein, Icahn School of Medicine at Mount Sinai, United States
Reviewed by: Gianluca Serafini, Ospedale San Martino (IRCCS), Italy; Etsuro Ito, Waseda University, Japan
*Correspondence: Katja Bertsch
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Borderline Personality Disorder (BPD) is a life-span mental disorder, which causes a high burden for the affected individuals and their social environment. Patients with BPD are characterized by instability in affect and interpersonal relationships, identity disturbance, and heightened impulsivity. Furthermore, deficits in emotion regulation as well as intense feelings of anger and difficulties in anger control belong to the core symptoms of BPD [American Psychiatric Association (APA), 2013]. In an effort to cope with strong negative feelings, such as anger, many BPD patients show self-destructive behaviors such as self-injury that commonly begins already in early adolescence (Zanarini et al.,
Previous cross-sectional and longitudinal studies have revealed emotion dysregulation and high levels of trait anger as important mediators of increased reactive aggression in BPD (Newhill et al.,
Although empirical research has confirmed the reliability and validity of BPD among adolescents (Kaess et al.,
Interestingly, Lawrence et al. (
Taken together, previous fMRI studies on emotion dysregulation as well as anger and aggression in BPD have by the majority focused on adult samples and only little is known about the neural correlates of these aspects of the symptomatology in the early stage of the disorder. Considering the formerly reported structural alterations as well as deficient self-reported emotion regulation in adolescents with BPD, we also assume functional abnormalities in brain circuits involved in the regulation of emotions, such as anger, in this early stage of BPD. In improving our understanding of the neural correlates associated with the symptomatology, we hope to contribute to an early implementation of appropriate therapeutic interventions for adolescents with BPD.
The aim of the present study was to investigate neural correlates of rejection-related feelings of anger and of subsequent other-directed or self-directed aggressive reactions in female adolescent BPD patients in order to contribute to a better understanding of the etiology of disturbed emotion regulation in BPD. Given the fact that most of the psychiatric in- and out-patients with BPD is female and most of previous research has focused on female adult and adolescent BPD patients, we decided to focus on an all-female sample in this first fMRI study on anger and aggression in adolescents with BPD knowing the importance of investigating sex-dependent effects in further studies.
We used a script-driven imagery paradigm with scripts describing a social rejection/exclusion situation and the elicited intense feelings of anger followed by descriptions of self-directed aggressive reactions or aggressive reactions against the rejecting person. Based on previous findings in adolescents with BPD and similar to adult BPD patients, we expected a heightened emotional responding in adolescents with BPD compared to an age-matched healthy control group. We hypothesized that the latter would be reflected in a hyperactivation in the amygdala and the insula in adolescents with BPD compared to adolescent healthy controls when listening to the scripts describing anger inducing rejection situations as well as aggressive behavior. Furthermore, we hypothesized to find reduced activations in prefrontal regions, such as the OFC reflecting deficits in the regulation of highly arousing states of negative emotion in adolescents BPD compared to healthy adolescents. Consistently, we expected adolescents with BPD to score higher on the ratings for feelings of anger after listening to the scripts.
Twenty female adolescents with BPD (Y-BPD; age 15–17 years) and 20 female adolescent healthy controls (Y-HC; age 15–17 years) took part in the study. The study also comprised 34 female adults with BPD (A-BPD; age 18–50 years) and 32 female adult healthy controls (A-HC; age 18–50 years). The adult sample was almost identical with the female sample reported by Herpertz et al. (
All adolescent and adult BPD patients currently met at least 5 out of 9 BPD criteria according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV, American Psychiatric Association,
Sample description and self-report data.
Age (years) | 16.35 | 0.88 | 15.85 | 0.81 | 25.69 | 5.08 | 27.33 | 6.37 | ||||
Raven | 50.55 | 4.55 | 52.89 | 4.65 | 53.46 | 4.29 | 53.40 | 4.43 | ||||
ZAN-BPD total score | 17.40 | 5.86 | 0.00 | 0.00 | 11.76 | 4.86 | 0.39 | 0.80 | ||||
AQ total score | 62.75 | 16.91 | 41.32 | 8.08 | 61.12 | 11.92 | 43.39 | 7.83 | ||||
STAXI trait anger | 21.19 | 8.31 | 14.11 | 4.47 | 23.82 | 5.87 | 14.40 | 3.58 | ||||
DERS total score | 109.56 | 34.11 | 56.00 | 11.13 | 123.55 | 16.14 | 63.85 | 14.14 | ||||
BIS total score | 75.81 | 14.32 | 57.22 | 8.52 | 77.17 | 12.09 | 60.49 | 10.46 | ||||
FDS total score | 20.85 | 15.39 | 3.62 | 3.32 | 19.26 | 12.12 | 2.93 | 2.35 | ||||
Affective disorders | 12 (60%) | 10 (50%) | 0 | 0 | 31 (91%) | 11 (32%) | 0 | 0 | ||||
Substance ass. disorders | 1 (5%) | 0 (0%) | 0 | 0 | 6 (18%) | 0 (0%) | 0 | 0 | ||||
Anxiety disorders | 4 (20%) | 5 (25%) | 0 | 0 | 20 (59%) | 15 (44%) | 0 | 0 | ||||
PTSD | 1 (5%) | 1 (5%) | 0 | 0 | 9 (27%) | 8 (24%) | 0 | 0 | ||||
Somatoform disorders | 0 (0%) | 0 (0%) | 0 | 0 | 5 (15%) | 5 (15%) | 0 | 0 | ||||
Eating disorders | 8 (40%) | 4 (20%) | 0 | 0 | 20 (59%) | 13 (38%) | 0 | 0 | ||||
Antisocial PD | 0 (0%) | 0 (0%) | 0 | 0 | 1 (3%) | 1 (3%) | 0 | 0 | ||||
Avoidant PD | 0 (0%) | 0 (0%) | 0 | 0 | 0 (0%) | 0 (%) | 0 | 0 |
Recruitment was done by the central project of the KFO 256 (Schmahl et al.,
All patients and healthy controls took part in an extensive on-site diagnostic interview to assess BPD and other current and lifetime psychiatric disorders. Interviews consisted of the Structured Clinical Interview for DSM-IV disorders (SCID-I; Wittchen et al.,
We used a script-driven imagery task with participants listening to eight standardized scripts, each consisting of four separate phases: baseline, anger induction, other-directed/self-directed aggression, relaxation. The anger induction phase was based on narratives of interpersonal rejection, the other-directed aggression phase comprised narratives of directing physical aggression toward another person, the self-directed aggression phase narratives of self-harming behavior. Each participant listened to four scripts containing narratives of aggressive behavior against others and four scripts describing aggressive behavior against oneself, with order of presentation of the two script types being pseudo-randomized. Within each script, the duration of each of the four phases was 25 s and the duration of the inter-phase interval was 8 s. The scripts were lively read by professional actors and participants were instructed to imagine the described scenes as vividly as possible in order to provoke intense emotional responses. Each of the eight scripts was followed by self-ratings on 5-point Likert scales asking for feelings of anger after the anger induction phase, feelings of anger after the aggression phase as well as for levels of dissociation, derealization, and vividness of imagination. The self-ratings were followed by a 20 s inter-script interval.
Data acquisition was performed in a 3T Tim Trio whole-body scanner (Siemens, Erlangen, Germany) equipped with a 32-channel head coil. Forty transverse slices were acquired in each volume using a T2*-sensitive gradient EPI sequence (
Self-report and self-rating data were analyzed using SPSS 20.0 using
FMRI data were preprocessed and analyzed in SPM8 under Matlab R2012b. Standard data preprocessing comprised temporal adjustment for differences in slice time acquisition, motion correction, co-registration of EPI images with T1-weighted structural images, segmentation of structural images, normalization into MNI space, and spatial smoothing with an 8-mm full-width-half-maximum (FWHM) kernel. On the first level we set up a general linear model (GLM) for each participant with baseline, anger, other-directed aggression, self-directed aggression, relaxation and rating as regressors as well as 6 motion regressors; we defined the contrasts baseline, anger, other-directed aggression and self-directed aggression for each participant. On the second level, we entered these contrasts into a group (BPD, HC) × age (adolescent, adult) × phase (baseline, anger, other-directed aggression, self-directed aggression) full-factorial model. Since we were primarily interested in neural correlates of anger and aggression in adolescents with BPD and differences between adults with and without BPD are reported elsewhere (Herpertz et al.,
Adolescents with BPD reported significantly higher levels of BPD symptoms, aggressiveness, trait anger, emotion dysregulation, impulsivity, and dissociation than healthy adolescent controls [all
Adolescents with BPD did not differ significantly from healthy adolescent controls in their subjective anger ratings after the rejection-based anger induction phase or the aggression phase, the vividness of imagination, or subjective derealization [
Self-rating data.
Anger after provocation | 3.54 | 0.87 | 3.63 | 0.54 | 3.66 | 0.63 | 3.24 | 0.98 | −0.58 | 0.564 | 1.29 | 0.259 |
Anger after aggression | 3.43 | 1.04 | 3.23 | 0.87 | 3.64 | 0.79 | 2.69 | 1.04 | 0.65 | 0.522 | 4.26 | 0.041 |
Derealisation | 2.28 | 1.02 | 1.74 | 0.80 | 2.26 | 1.04 | 1.42 | 0.81 | 2.06 | 0.046 | 1.37 | 0.244 |
Dissociation | 2.13 | 1.09 | 1.36 | 0.60 | 2.06 | 0.97 | 1.26 | 0.71 | 3.04 | 0.005 | 0.10 | 0.757 |
Vividness of imagination | 2.89 | 0.99 | 3.34 | 1.09 | 2.86 | 0.85 | 2.52 | 1.34 | −1.51 | 0.139 | 3.04 | 0.084 |
Y-BPD showed higher activation in a large cluster comprising parts of the left insula, putamen and claustrum (peak voxel [x, y, z]: −32, −10, 10;
Full-Factorial Analysis, whole brain results during anger induction phase,
Y-BPD > Y-HC | Left insula, left putamen, left rolandic operculum, claustrum | 394 | <0.001 | 3.62 | 3.59 | −32 | −10 | 10 |
Y-HC > Y-BPD (Y-BPD>Y-HC) > (A-BPD>A-HC) | No significant results left postcentral gyrus, left precuneus | 102 | <0.001 | 4.20 | 4.15 | −30 | −36 | 68 |
(Y-HC>Y-BPD) > (A-HC>A-BPD) | No significant results |
fMRI results for anger, other-directed aggression and self-directed aggression phase. This figure displays whole brain results (
Y-BPD showed higher activation in a large cluster including parts of the left insula, putamen, opercular part of the inferior frontal gyrus, middle and superior temporal gyri, pallidum, precuneus, thalamus, and hippocampus (peak voxel [x, y, z]: −34, −48, 8;
Full-Factorial Analysis, whole brain results during other-directed aggression phase,
Y-BPD > Y-HC | Left insula, left putamen, left rolandic operculum, left heschl gyrus, left inferior frontal gyrus opercular part, left middle temporal gyrus, left pallidum, left superior temporal gyrus, left precuneus, left calcarine fissure, left thalamus, left hippocampus | 1,963 | <0.001 | 5.03 | 4.95 | −34 | −48 | 8 |
Y-HC > Y-BPD | Right middle temporal gyrus, right superior temporal gyrus | 430 | <0.001 | 4.48 | 4.42 | 42 | −48 | 10 |
Right caudate | 100 | <0.001 | 4.04 | 4.00 | 22 | 28 | 0 | |
(Y-BPD>Y-HC) > (A-BPD>A-HC) | Left insula, left putamen, left rolandic operculum, left inferior frontal gyrus opercular part, left inferior frontal gyrus triangular part, left pallidum | 1,050 | <0.001 | 4.11 | 4.06 | −30 | −12 | 8 |
(Y-HC>Y-BPD) > (A-HC>A-BPD) | Right middle temporal gyrus, right superior temporal gyrus | 126 | <0.001 | 3.69 | 3.66 | 52 | −46 | 8 |
When comparing Y-BPD to Y-HC, we found higher activation in a cluster including the left putamen and insula (peak voxel [x, y, z]: −32, −10, −2;
Full-factorial analysis, whole brain results during self-directed aggression phase,
Y-BPD > Y-HC | Left putamen, left insula | 178 | <.001 | 3.74 | 3.71 | −32 | −10 | −2 |
Left middle temporal gyrus | 93 | <0.001 | 3.68 | 3.65 | −50 | −28 | 0 | |
Y-HC > Y-BPD | No significant results | |||||||
(Y-BPD>Y-HC) > (A-BPD>A-HC) | No significant results | |||||||
(Y-HC>Y-BPD) > (A-HC>A-BPD) | No significant results |
This is the first fMRI study investigating neural correlates of rejection-related feelings of anger and reactive aggression in adolescent BPD patients. Using a script-driven imagery setting to induce feelings of anger, and descriptions of subsequent aggressive reactions, we found increased activations in the left posterior insula and left dorsal striatum as well as in the inferior frontal gyrus and parts of the mentalizing network in female adolescents with BPD compared to female age-matched healthy controls. At least for the other-directed aggression phase, this pattern of activation could only be found in the adolescent sample suggesting specific alterations for adolescents with BPD. Together with previous studies, these findings suggest an enhanced emotional reactivity to interpersonal threat- or rejection-related situations early in the development of BPD. Since deficient emotion regulation has emerged an important mediator for aggression in BPD, the current findings support the need of early and specific interventions for affected adolescents.
Listening to anger-inducing descriptions of interpersonal rejection resulted in stronger activations in large clusters including the left posterior insula and the left dorsal striatum, mainly the putamen, in adolescents with BPD compared to healthy adolescents. Similar patterns of increased activations in the left insula and putamen, but also the middle temporal gyrus, were also found in adolescents with BPD during the descriptions of self-directed aggressive behaviors. Furthermore, the imagination of acting out aggressively against the rejecting person also caused elevated activations in large clusters including the left posterior insula and putamen, the middle temporal gyrus reaching into the superior temporal gyrus, the pallidum, precuneus, thalamus, hippocaumpus, and the inferior frontal gyrus. Notably the results of the group by age interaction indicate that the latter effect is characteristic for adolescents with BPD.
Increased left posterior insula activation indicates enhanced emotional reactivity to anger-inducing descriptions of interpersonal rejection and subsequent behavioral responses in terms of aggression directed against the own or the rejecting person in adolescents with BPD. The insula has been found to be crucially involved in the detection and processing of emotionally salient stimuli (Mühlberger et al.,
Support for the interpretation that interpersonal rejection may be more painful and hence salient for adolescents with BPD than healthy adolescents also comes from enhanced activations in the left dorsal striatum (putamen) as this region is involved in the coding of stimulus saliency (Zink et al.,
Contrary to our hypotheses and to previous studies in adults with BPD (Schulze et al.,
Interestingly, adolescents with BPD showed a heightened activation in the inferior frontal gyrus in response to descriptions of aggressive reactions against others. As the inferior frontal gyrus has been associated with different forms of self-control and self-regulation, including the regulation of emotion in general (Lieberman,
On a behavioral level, the rating data did not reveal significant differences for the anger ratings between adolescents with BPD and healthy adolescents, which is contrary to our hypothesis. Interestingly healthy adolescents compared to adult healthy controls showed higher anger ratings when listening to descriptions of aggressive behavior, indicating a heightened emotional responding not only in adolescents with BPD but also in healthy adolescents. This might explain why the two adolescent groups did not differ in their anger ratings on the behavioral level, although they showed significant differences in neural activation.
Taken together, the fMRI data suggest a stronger salience of interpersonal rejection in adolescents with BPD associated with higher levels of social pain. Elevated activations in the thalamus and hippocampus suggest an even stronger activation of bottom-up emotion generation and memory retrieval despite high effort to mentalize and control feelings of anger. Considering heightened anger ratings also in healthy adolescents, the fMRI results indicate a level of emotion dysregulation in adolescents with BPD that goes beyond regular emotion regulation difficulties in adolescence (Guyer et al.,
The experimental paradigm and the possibility to compare the findings in adolescents to those of an adult sample are major advantages of the current study. Nevertheless, several shortcomings need to be mentioned. First, we were only able to include
Third, a clinical control group would be needed to address the specificity of the current findings for adolescents with BPD. Fourth, although the majority of our participants were medication-free, we cannot rule out that antidepressant medication in
Our results suggest a stronger salience of interpersonal rejection and subsequent aggressive reactions in female adolescents with BPD compared to age-matched healthy female controls. A heightened emotional reactivity to interpersonal rejections might thus be already apparent at early developmental stages of BPD. A question that arises from the current findings is if the stronger emotional reaction to interpersonal rejection in adolescents with BPD is related to real experiences of former peer rejection. This aspect should be further addressed in future studies. In a therapeutic context it could be helpful for adolescents with BPD to develop functional strategies to regulate negative emotions, such as intense feelings of anger. So far, interventions from dialectical behavioral therapy for adolescents (DBT-A; Rathus and Miller,
MaK has contributed substantially to acquisition, analysis, and interpretation of the data. She has drafted the article. KU has contributed substantially to analysis and interpretation of the data. RB and MiK have contributed to conception and design as well as the interpretation of data. They have revised the manuscript critically for important intellectual content. SH has contributed substantially to acquisition of the data. She has revised the manuscript critically for important intellectual content. SCH and KB have contributed substantially to conception and design as well as the interpretation of data. They have revised the manuscript critically for important intellectual content. All authors gave final approval of the version to be published.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The study was part of the Clinical Research Group KFO 256 supported by the German Research Foundation (Schmahl et al.,