Elsevier

Biological Psychiatry

Volume 54, Issue 11, 1 December 2003, Pages 1284-1293
Biological Psychiatry

Original article
Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation

https://doi.org/10.1016/S0006-3223(03)00636-XGet rights and content

Abstract

Background

Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD.

Methods

Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department.

Results

Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening.

Conclusions

Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.

Introduction

Acore problem of borderline personality disorder (BPD) is emotional dysregulation Clarkin et al., 1993, Sanislow et al., 2000, which results from a combination of emotional vulnerability and an inability to modulate emotional responses Gunderson and Zanarini, 1989, Linehan, 1993, Linehan, 1995. Emotional vulnerability is characterized by a marked sensitivity to emotional stimuli (low threshold) and unusually strong reactions (high amplitude) that are abnormally slow in returning to baseline (long duration). According to Linehan (1995), “… most of the problems exhibited by borderline individuals are either the direct or indirect consequence of emotion dysregulation or attempts to modulate intense emotional reactions.” From this perspective, many of the erratic self-destructive, impulsive, or self-injurious behaviors that are part of the constellation of symptoms of BPD might be understood as products of emotional dysregulation. Most often (and most dramatically), these are manifest in the context of a pattern of unstable and intense interpersonal relationships (DSM-IV, criterion 2, p. 654 [American Psychiatric Association 1994]; also see Benjamin 1993 and Linehan 1993).

Findings from a diverse range of animal and human experiments indicate that the amygdala is an element of brain systems involved in the generation of negative emotional states Amaral, 2002, Davis, 2000, Emery et al., 2001, LeDoux, 2000, Meunier et al., 1999. It is often hyperactive in mood and emotional disorders, such as posttraumatic stress disorder (PTSD) (Rauch et al 2000), depression (Drevets 1998), and generalized anxiety disorder (Johnstone et al, unpublished data; Thomas et al 2001). Humans with selective bilateral damage to the amygdala show impaired fear conditioning (Bechara et al 1995), a failure to show enhanced perception of stimuli with aversive content (Anderson and Phelps 2001), and impairments in making negative evaluations of human faces that have been rated untrustworthy and unapproachable by normal subjects (Adolphs et al 1998). In social situations, the amygdala is thought to play an important role in modulating attention/vigilance (especially in evaluating potentially threatening social situations), the valence of events/objects, and perceiving the emotional expressions of others Amaral, 2002, Rolls, 1999, Whalen, 1998. For these reasons, we take the amygdala as a starting point for developing a brain-system-level model of vigilance and negative emotional states and for identifying abnormalities within these systems that are responsible for emotional dysregulation.

Research on BPD in which imaging technologies are used to assess amygdala function is limited. Positron emission tomography studies have found hypometabolism in prefrontal cortex (PFC) of BPD patients compared with normal control (NC) subjects De la Fuente et al., 1997, Soloff et al., 2000 and above-normal activation of dorsolateral PFC and anterior PFC when BPD patients were presented with scripts designed to evoke memories of abandonment (Schmahl et al 2003). In a magnetic resonance spectroscopy study, Tebartz van Elst et al (2001) observed decreased levels of N-acetyl aspartate (suggestive of impaired neural functioning) in BPD patients compared with NC subjects in the dorsolateral PFC. Structural magnetic resonance imaging (MRI) studies have found smaller frontal lobe volume in BPD patients (Lyoo et al 1998) and reduced hippocampal and amygdala volume (Dreissen et al 2000). In the one functional MRI (fMRI) study that we are aware of, Herpertz et al (2001) reported greater amygdala activation in six BPD patients without co-occurring Axis 1 disorders, compared with NC subjects, when they viewed aversive slides (e.g., mutilated bodies) relative to neutral slides (e.g., household objects).

To assess amygdala reactivity in BPD subjects, we selected pictures of human facial expressions of emotion (Ekman and Friesen 1979) that have been shown in imaging studies to activate the amygdala in NC subjects and elicit abnormal levels of activity in individuals with mood and anxiety disorders. For example, a number of laboratories have demonstrated that fearful faces activate the amygdala in NC subjects Breiter et al., 1996, Morris et al., 1996, Vuilleumier et al., 2001, Whalen et al., 1998, as well as in individuals with anxiety disorders (Thomas et al 2001) and PTSD (Rauch et al 2000; however there was no assessment for Axis II disorders). We predicted that differences in amygdala activation between the BPD and NC groups would be greatest to faces with negative emotional valences.

Section snippets

Subjects

Subjects were recruited by advertisements placed in the community and on treatment units at affiliated clinical sites. The NC group comprised 15 right-handed subjects, nine (60%) of whom were female; the BPD group comprised 15 right-handed subjects, 13 (86%) of whom were female [χ2(3) = 1.5, p = .107]. Mean (SD) age was 35.0 (11.7) years for the BPD group and 34.9 (10) for the NC group [F(1,28) = .001, p = .99]; see Table 1. All subjects included in the BPD group were currently in psychiatric

Right and left amygdala activation

Borderline personality disorder patients exhibited high levels of left amygdala activation to the facial expressions (relative to the fixation point; Figure 2). Other areas that showed suprathreshold activation in Figure 2 include regions containing the dorsal border of the amygdala, the bed nucleus of the stria terminalis, the lateral hypothalamic nuclei, the nucleus basalis, and regions in the frontal lobes. For the NC subjects, the facial expressions activated the left amygdala relative to

Discussion

The amygdala is one of the most studied brain regions in behavioral neurobiology and is thought to be a critical element in the systems that generate fear/anxiety and the systems that modulate vigilance. Our finding, that left amygdala reactivity is abnormal in BPD patients (compared with NC subjects), is consistent with findings that the amygdala is also hyperreactive in mood and anxiety disorders Drevets, 1998, Rauch et al., 2000, Thomas et al., 2001 and consistent with animal laboratory

Acknowledgements

This work was supported in part by the Borderline Personality Disorder Research Foundation and National Institutes of Health Grant MH-01654 (THM).

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