Neural correlates of emotion processing in borderline personality disorder☆
Introduction
Emotional instability is one of the most striking features of borderline personality disorder (BPD) and is central to many of the behavioral and interpersonal symptoms of the disorder (Stone, 1988, Linehan, 1993), including some of the most disabling, even life-threatening, symptoms of BPD, such as suicidality, outbursts of intense anger, stormy relationships, and identity disturbances (Koenigsberg et al., 2001). This emotional instability may be related to a heightened attention or sensitivity to social–emotional cues in interpersonal senarios (Wagner and Linehan, 1999, Meyer et al., 2004, Taylor and Fragopanagos, 2005, Lynch et al., 2006), a tendency to self-referential emotional processing (Schnell et al., 2007), or to dysregulated emotional processing mechanisms (Phillips et al., 2003b). Understanding the nature of the disturbances in emotion processing in BPD may provide important insights into the mechanisms of affective instability, the underlying pathology of the disorder, understanding disorder, and the relationship between BPD and the Axis I mood disorders, as well as helping to identify endophenotypes that could focus genetic studies of BPD, and target biological or psychological treatments to more specifically address affective instability in BPD.
Neuroimaging studies have begun to identify networks that are engaged in emotion processing in healthy individuals and in those with disturbed affect. A number of studies have employed images from the International Affective Pictures System (IAPS; Lang et al., 2001) as emotional stimuli. The IAPS is a set of positive, negative and neutral valence pictures for which normative data for picture valence and arousal level are available. In healthy individuals, viewing of emotional pictures is associated with activation in the visual cortex (Takahashi et al., 2004, Britton et al., 2006), ventromedial prefrontal cortex and medial orbitofrontal cortex (Northoff et al., 2000, Takahashi et al., 2004, Britton et al., 2006, Grimm et al., 2006), anterior cingulate (Takahashi et al., 2004, Grimm et al., 2006), dorsolateral prefrontal cortex (Northoff et al., 2000, Grimm et al., 2006), amygdala-hippocampal region (Takahashi et al., 2004, Britton et al., 2006) and basal ganglia (Takahashi et al., 2004). Differences in activation patterns in these regions have been identified in schizophrenic subjects with and without affective flattening (Takahashi et al., 2004), phobics (Goossens et al., 2007), and individuals high in neuroticism (Britton et al., 2007).
Little is known about the neurobiological underpinnings of the emotional instability in BPD, but the BPD syndrome itself has been associated with regional hypometabolism and deficits in serotonergic activity (De La Fuente et al., 1997, Siever et al., 1999, Soloff et al., 2000, Leyton et al., 2001, New et al., 2002, Juengling et al., 2003). Structural magnetic resonance imaging (MRI) studies have found smaller amygdala, hippocampal (Driessen et al., 2000, Schmahl et al., 2003, Tebartz van Elst et al., 2003), anterior cingulate (Tebartz van Elst et al., 2003, Hazlett et al., 2005) and orbitofrontal cortex (Tebartz van Elst et al., 2003) volumes in BPD patients compared with controls. Two functional neuroimaging studies of borderline patients performing an emotion-relation task have been reported. In the first, BOLD functional MRI (fMRI) was performed in six BPD patients and controls as they viewed negative or neutral pictures (inanimate objects). Compared with healthy controls, the BPD patients showed an increased activation of the amygdala bilaterally and of the medial and inferolateral prefrontal cortex when viewing the negative versus the neutral images (Herpertz et al., 2001). The second study examined the processing of facial expressions of emotion (Donegan et al., 2003). The BPD patients showed increased left amygdala activation to fearful, sad, happy and neutral faces.
The emotional instability in BPD is associated with emotional reactivity to social events (Stiglmayr et al., 2005), yet the neuroimaging studies of emotion processing in BPD have thus far been confined to studies of face perception (Donegan et al., 2003) and to scenes intermixing social and non-social stimuli (e.g. images of attacking animals, offensive insects and reptiles, and disfigured bodies), making it impossible to characterize the processing of social cues in particular. This is a serious limitation since social and non-social emotional stimuli are processed differently in the brain (Britton et al., 2006). The present study represents an important advance because of its focus on social emotional processing in particular.
A network comprising the amygdala, fusiform gyrus, superior temporal sulcus (STS), primary visual regions, and the prefrontal cortex has been implicated in visual social emotional cognition (Allison et al., 2000, Adolphs and Spezio, 2006, Bokde et al., 2006). This model posits that visual social stimuli are processed by the fusiform face area in interaction with the STS, which attributes motivation and social intension. Emotional salience is then assigned by the amygdala, together with other prefrontal areas such as the insula. The amygdala, via feedback loops to the STS and more primary visual areas, may activate attentional amplification (Allison et al., 2000) to relevant features of the stimuli. Building upon this formulation, Satpute and Lieberman (2006) have proposed a dual-process model of social cognition in which there is a division between “reflexive” and “reflective” neural systems. The former, including the amygdala, STS, orbitofrontal (OFC) cortex, dorsal anterior cingulate (dACC) and basal ganglia, provides an automatic, fast operating emotional response, while the latter, incorporating the lateral and medial prefrontal areas, the medial temporal lobe and the rostral anterior cingulate (rACC), provides a more nuanced, experience-based, but slower-responding emotional appraisal. We hypothesize that the increased emotional reactivity characteristic of BPD patients may be a consequence of their inability to adequately engage the reflective system and thus to rely heavily upon the more primitive reflexive system. This model would imply that when processing social emotional stimuli, BPD patients compared with healthy subjects would show greater activation of the amygdala, fusiform gyrus, primary visual areas, STS, dACC and OFC, while healthy subjects would demonstrate greater activation of lateral and medial prefrontal areas and medial temporal regions compared with BPD subjects. To test these hypotheses, we obtained BOLD fMRI in BPD patients and healthy volunteers as they viewed social emotional pictures.
Section snippets
Subjects
Subjects were 19 BPD patients and 17 healthy volunteers (HC) recruited from the outpatient clinics at the Mount Sinai Medical Center in New York City, and the Bronx Veterans Affairs Medical Center, and by advertisements in local newspapers. They were male and female between 18 and 50 years of age. BPD subjects met DSM-IV criteria for BPD and had prominent affective instability as evidenced by the presence of three of four BPD criteria associated with affective instability (Koenigsberg et al.,
Self-report
The manipulation check confirmed that the positive and negative pictures elicited emotional reactions of the expected valence. For the BPD subjects, the mean SAM valence rating for the negative pictures was 7.18 ± 0.19 and 3.63 ± 0.17 for the positive pictures. The healthy controls rated the negative pictures at 7.49 ± 0.19 and the positive pictures at 3.50 ± 0.17. A repeated measures analysis of variance (ANOVA) with SAM valence rating as the dependent variable, IAPS picture valence category (positive
Discussion
The manipulation check confirmed that the IAPS pictures selected as negative in valence were in fact experienced by the subjects as negative and as significantly more negative than the pictures selected as positive. There were no group differences in the ratings of valence or arousal of the pictures. Nevertheless, the BPD subjects and the normal controls showed different patterns of neural activation during the processing of the emotional pictures. These observations are similar to those of
Acknowledgements
This work was supported by Grant Number MO1-RR-00071 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and the Mental Illness Research Education and Clinical Center, VISN 3 Veterans Health Administration, and an educational grant from the Siemens Medical Systems, Inc. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR, NIH, or the VA. We thank Dr. Sergei Pakhomov
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Presented in part at the Annual Meeting of the Society for Biological Psychiatry, San Diego, CA, May 2007.