Neuronal correlates of altered empathy and social cognition in borderline personality disorder Isabel Dziobek a, b, ⁎ , 1 , Sandra Preißler c, 1 , Zarko Grozdanovic d , Isabella Heuser b, c , Hauke R. Heekeren a, b , Stefan Roepke b, c, ⁎⁎ a Max-Planck-Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany b Cluster of Excellence Languages of Emotion, Freie Universität Berlin, Habelschwerdter Allee 45, 14195 Berlin, Germany c Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany d Department of Radiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany abstract article info Article history: Received 6 July 2010 Revised 1 April 2011 Accepted 3 May 2011 Available online 7 May 2011 Keywords: Borderline personality disorder Social cognition Empathy fMRI Borderline personality disorder (BPD) is a severe psychiatric condition of undetermined brain underpinnings, which involves profound emotion regulation deficits and interpersonal impairment. To elucidate biopsycho- logical markers of the disorder, we performed two studies: i.) assessing empathy and social cognition and ii.) measuring the psychophysical properties and functional brain correlates of empathic functioning in a total of fifty-one affected patients and 50 age- and gender-matched controls. In the behavioral study we applied the Multifaceted Empathy Test (MET), a new, ecologically valid measure to assess cognitive (i.e., social cognition) and emotional (i.e., empathic concern) empathy to a subset of participants. In the second study, functional Magnetic Resonance Imaging and skin conductance measurements were performed while participants took a scanner-adapted version of the MET. Patients with BPD showed impairments in cognitive and emotional empathy. Brain responses during cognitive empathy were significantly reduced in patients compared to controls in the left superior temporal sulcus and gyrus (STS/STG), where this reduction was associated with levels of intrusive symptomatology in the BPD group. During emotional empathy, patients with BPD exhibited greater brain activity than controls in the right middle insular cortex, a response that was associated with skin conductance responses in the patients. Results indicate that altered functioning of the STS/STG and insula represents pathophysiological mediators for reduced empathy in BPD, with an important role for intrusive symptomatology and levels of arousal. The findings thus support a conceptualization of BPD as involving deficits in both inferring others' mental states and being emotionally attuned to another person. © 2011 Elsevier Inc. All rights reserved. Introduction Borderline personality disorder (BPD) is a severe psychiatric disorder with high mortality, affecting up to 5.8% of the general population (Grant et al., 2008). While in the population based studies men and women are affected in equal proportion (Grant et al., 2008), the clinical population mainly consists of young women (Zanarini et al., 2006). Despite long term impairment in social functioning in many patients (Zanarini et al., 2010), the disorder has high rates of remission of symptoms (Zanarini et al., 2006) and thus is rare after the age of mid- forties (Grant et al., 2008). BPD is characterized in the DSM-IV-TR (text revision of the Diagnostic and Statistical Manual of Mental Disorders, DSM, IV; American Psychiatric Association, 2000) by pervasive instability in moods, interpersonal relationships, and behavior. The pattern of instability in relationships has persisted for years and is in many cases closely related to disturbance in the person's early social interactions (e.g. Lobbestael et al., 2010; Preißler et al., 2010). The instability often disrupts family and professional life, and the indivi- dual's sense of self-identity. Patients with BPD often have other comorbid psychiatric disorders, one prominent among them being posttraumatic stress disorder (PTSD), which is present in up to 56% of affected individuals (e.g. Zanarini et al., 1998). In fact, BPD has been shown to be associated with childhood traumatic experiences, especially sexual abuse (Lobbestael et al., 2010). Sexual traumatic events are reported in BPD patients with PTSD (31.0%) and without PTSD (22.8%; Harned et al., 2010). High percentage of full symptom PTSD and subsyndromal PTSD (Harned et al., 2010) are reflected among others in severe suffering from intrusions in adulthood in BPD patients. NeuroImage 57 (2011) 539–548 ⁎ Correspondence to: I. Dziobek, Cluster of Excellence “Languages of Emotion”, Freie Universität Berlin, Habelschwerdter Allee 45, 14195 Berlin. Fax: + 49 30 838 52887. ⁎⁎ Correspondence to: S. Roepke, Department of Psychiatry, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany. Fax: +49 30 8445 8365. E-mail addresses: isabel.dziobek@fu-berlin.de (I. Dziobek), s.preissler@uni-jena.de (S. Preißler), zarko.grozdanovic@charite.de (Z. Grozdanovic), isabella.heuser@charite.de (I. Heuser), hauke.heekeren@fu-berlin.de (H.R. Heekeren), stefan.roepke@charite.de (S. Roepke). 1 Both authors contributed equally to this article. 1053-8119/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2011.05.005 Contents lists available at ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg