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Supplementary MaterialsEuropean Archives of Psychiatry and Clinical NeuroscienceDeficient amygdala-prefrontal intrinsic connectivity after effortful emotion regulation in borderline personality disorderBlazej M. Baczkowski, Linda van Zutphen*, Nicolette Siep, Gitta A. Jacob, Gregor Domes, Simon Maier, Andreas Sprenger, Alena Senft, Bastian Willenborg, Oliver Tüscher, Arnoud Arntz, & Vincent van de Ven* Corresponding authorDept. of Clinical Psychological Science, Faculty of Psychology and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The NetherlandsEmail: linda.vanzutphen@maastrichtuniversity.nlSupplementary MaterialsMethods and MaterialsThe text below is almost identical to van Zutphen et al, [submitted] because it is a part of a larger study performed by the same research group.ParticipantsBorderline personality disorder (BPD) and Cluster-C personality disorder (CPD) patients were recruited from the mental health clinics at local sites: the Virenze-Riagg in Maastricht (the Netherlands), PsyQ in Heerlen (the Netherlands), the borderline treatment unit of the Department of Psychiatry and Psychotherapy at the Medical Center Freiburg (Germany), the Department of Psychiatry and Psychotherapy at the University Hospital Lübeck (Germany) and the Institute for Behavior Therapy Training Hamburg (Germany). BPD patients were taking part in an international multicenter RCT on group schema therapy for BPD ADDIN EN.CITE <EndNote><Cite><Author>Wetzelaer</Author><Year>2014</Year><RecNum>6011</RecNum><Prefix>for detailed description`, </Prefix><DisplayText>[for detailed description, 1]</DisplayText><record><rec-number>6011</rec-number><foreign-keys><key app="EN" db-id="0arwf0asazr0rkea9dcvvwdjzrv000x29w0w">6011</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wetzelaer, P.</author><author>Farrell, J.</author><author>Evers, S. M.</author><author>Jacob, G. A.</author><author>Lee, C. W.</author><author>Brand, O.</author><author>van Breukelen, G.</author><author>Fassbinder, E.</author><author>Fretwell, H.</author><author>Harper, R. P.</author><author>Lavender, A.</author><author>Lockwood, G.</author><author>Malogiannis, I. A.</author><author>Schweiger, U.</author><author>Startup, H.</author><author>Stevenson, T.</author><author>Zarbock, G.</author><author>Arntz, A.</author></authors></contributors><titles><title>Design of an international multicentre RCT on group schema therapy for borderline personality disorder</title><secondary-title>BMC Psychiatry</secondary-title><alt-title>BMC psychiatry</alt-title></titles><periodical><full-title>BMC Psychiatry</full-title><abbr-1>BMC psychiatry</abbr-1></periodical><alt-periodical><full-title>BMC Psychiatry</full-title><abbr-1>BMC psychiatry</abbr-1></alt-periodical><pages>319</pages><volume>14</volume><dates><year>2014</year></dates><isbn>1471-244X (Electronic)
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ADDIN EN.CITE.DATA [2], and because in mental health care borderline personality disorder is more often diagnosed in females. We excluded homosexual females, because we used heterosexual erotic stimuli. General exclusion criteria were lifetime psychotic or bipolar disorder type-I, attention-deficit/hyperactivity disorder, dissociative identity disorder, serious and/or unstable medical illness, substance dependence needing clinical detoxification and fMRI exclusion criteria (i.e. claustrophobia, metal objects, cardiac arrhythmia, epilepsy, tattoos at neck/head and pregnancy).BPD and CPD patients were diagnosed according to the DSM-IV criteria, using the Structural Clinical Interview (SCID) I ADDIN EN.CITE <EndNote><Cite><Author>First</Author><Year>1994</Year><RecNum>95</RecNum><DisplayText>[3]</DisplayText><record><rec-number>95</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">95</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>First, M.B.</author><author>Spitzer, R.L.</author><author>Gibbon, M.</author><author>Williams, J.B.W.</author></authors></contributors><titles><title>Structured clinical interview for DSM-IV axis I disorders (SCID-I)</title></titles><dates><year>1994</year></dates><pub-location>New York</pub-location><publisher>Biometric Research Department</publisher><urls></urls></record></Cite></EndNote>[3] and II ADDIN EN.CITE <EndNote><Cite><Author>First</Author><Year>1997</Year><RecNum>96</RecNum><DisplayText>[4]</DisplayText><record><rec-number>96</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">96</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>First, M.B.</author><author>Spitzer, R.L.</author><author>Gibbon, M.</author><author>Williams, J.B.W.</author><author>Benjamin, L.</author></authors></contributors><titles><title>Structured clinical interview for DSM-IV axis II personality disorders (SCID-II)</title></titles><dates><year>1997</year></dates><pub-location>New York</pub-location><publisher>Biometric Research Department</publisher><urls></urls></record></Cite></EndNote>[4], assessed by trained interviewers. BPD patients were further screened with the BPD Severity Index PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Bcm50ejwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+PFJl
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ADDIN EN.CITE.DATA [5-7], of which the score > 20 indicates an additional inclusion criterion for BPD ADDIN EN.CITE <EndNote><Cite><Author>Wetzelaer</Author><Year>2014</Year><RecNum>6011</RecNum><DisplayText>[1]</DisplayText><record><rec-number>6011</rec-number><foreign-keys><key app="EN" db-id="0arwf0asazr0rkea9dcvvwdjzrv000x29w0w" timestamp="1433509139">6011</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wetzelaer, P.</author><author>Farrell, J.</author><author>Evers, S. M.</author><author>Jacob, G. A.</author><author>Lee, C. W.</author><author>Brand, O.</author><author>van Breukelen, G.</author><author>Fassbinder, E.</author><author>Fretwell, H.</author><author>Harper, R. P.</author><author>Lavender, A.</author><author>Lockwood, G.</author><author>Malogiannis, I. A.</author><author>Schweiger, U.</author><author>Startup, H.</author><author>Stevenson, T.</author><author>Zarbock, G.</author><author>Arntz, A.</author></authors></contributors><titles><title>Design of an international multicentre RCT on group schema therapy for borderline personality disorder</title><secondary-title>BMC Psychiatry</secondary-title><alt-title>BMC psychiatry</alt-title></titles><periodical><full-title>BMC Psychiatry</full-title><abbr-1>BMC psychiatry</abbr-1></periodical><alt-periodical><full-title>BMC Psychiatry</full-title><abbr-1>BMC psychiatry</abbr-1></alt-periodical><pages>319</pages><volume>14</volume><dates><year>2014</year></dates><isbn>1471-244X (Electronic)
1471-244X (Linking)</isbn><accession-num>25407009</accession-num><urls><related-urls><url>;[1]. Narcissistic and antisocial personality disorder (PD), full or sub-threshold, were excluded for reasons related to the clinical trial in which the study sample participated ADDIN EN.CITE <EndNote><Cite><Author>Wetzelaer</Author><Year>2014</Year><RecNum>6011</RecNum><DisplayText>[1]</DisplayText><record><rec-number>6011</rec-number><foreign-keys><key app="EN" db-id="0arwf0asazr0rkea9dcvvwdjzrv000x29w0w" timestamp="1433509139">6011</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wetzelaer, P.</author><author>Farrell, J.</author><author>Evers, S. M.</author><author>Jacob, G. A.</author><author>Lee, C. W.</author><author>Brand, O.</author><author>van Breukelen, G.</author><author>Fassbinder, E.</author><author>Fretwell, H.</author><author>Harper, R. P.</author><author>Lavender, A.</author><author>Lockwood, G.</author><author>Malogiannis, I. A.</author><author>Schweiger, U.</author><author>Startup, H.</author><author>Stevenson, T.</author><author>Zarbock, G.</author><author>Arntz, A.</author></authors></contributors><titles><title>Design of an international multicentre RCT on group schema therapy for borderline personality disorder</title><secondary-title>BMC Psychiatry</secondary-title><alt-title>BMC psychiatry</alt-title></titles><periodical><full-title>BMC Psychiatry</full-title><abbr-1>BMC psychiatry</abbr-1></periodical><alt-periodical><full-title>BMC Psychiatry</full-title><abbr-1>BMC psychiatry</abbr-1></alt-periodical><pages>319</pages><volume>14</volume><dates><year>2014</year></dates><isbn>1471-244X (Electronic)
1471-244X (Linking)</isbn><accession-num>25407009</accession-num><urls><related-urls><url>;[1]. CPD patients were not allowed to score full or sub-threshold cluster-B PD, and > 2 BPD criteria. NPC did not meet DSM-IV criteria for any axis I or axis II disorder, as assessed by SCID-screeners ADDIN EN.CITE <EndNote><Cite><Author>First</Author><Year>1994</Year><RecNum>95</RecNum><DisplayText>[3, 4]</DisplayText><record><rec-number>95</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">95</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>First, M.B.</author><author>Spitzer, R.L.</author><author>Gibbon, M.</author><author>Williams, J.B.W.</author></authors></contributors><titles><title>Structured clinical interview for DSM-IV axis I disorders (SCID-I)</title></titles><dates><year>1994</year></dates><pub-location>New York</pub-location><publisher>Biometric Research Department</publisher><urls></urls></record></Cite><Cite><Author>First</Author><Year>1997</Year><RecNum>96</RecNum><record><rec-number>96</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">96</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>First, M.B.</author><author>Spitzer, R.L.</author><author>Gibbon, M.</author><author>Williams, J.B.W.</author><author>Benjamin, L.</author></authors></contributors><titles><title>Structured clinical interview for DSM-IV axis II personality disorders (SCID-II)</title></titles><dates><year>1997</year></dates><pub-location>New York</pub-location><publisher>Biometric Research Department</publisher><urls></urls></record></Cite></EndNote>[3, 4]. Positive items on screeners were checked with SCID interviews. Additional assessments involved the Brief Symptom Inventory ADDIN EN.CITE <EndNote><Cite><Author>Derogatis</Author><Year>1993</Year><RecNum>94</RecNum><DisplayText>[8]</DisplayText><record><rec-number>94</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">94</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Derogatis, L.R.</author></authors></contributors><titles><title>BSI Brief Symptom Inventory: Administration, Scoring, and Procedure Manual</title></titles><edition>4th</edition><dates><year>1993</year></dates><pub-location>Minneapolis, MN</pub-location><publisher>National Computer Systems</publisher><urls></urls></record></Cite></EndNote>[8], BPD checklist ADDIN EN.CITE <EndNote><Cite><Author>Arntz</Author><Year>1995</Year><RecNum>101</RecNum><DisplayText>[9]</DisplayText><record><rec-number>101</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">101</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Arntz, A.</author><author>Dreessen, L.</author></authors></contributors><titles><title>BPD-Klachtenlijst 47 [BPD Checklist]</title></titles><dates><year>1995</year></dates><pub-location>The Netherlands</pub-location><publisher>Maastricht University</publisher><urls></urls></record></Cite></EndNote>[9] and Interview for Trauma Events in Childhood PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb2JiZXN0YWVsPC9BdXRob3I+PFllYXI+MjAwOTwvWWVh
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ADDIN EN.CITE.DATA [10].Eight participants were excluded because of invalid, incomplete or unavailable data (3 BPD, 2 NPC, 3 CPD), five because of excessive head movement of more than 4 mm (2 BPD, 2 NPC, 1 CPD), two NPC had scores above .70 on the BSI and three CPD patients had scores above 100 on the BPD checklist. Eight participants (6 BPD, 1 NPC, 1 CPD) explicitly reported in the exit questionnaire that they fell asleep during any of the resting state runs, and therefore were excluded. Three BPD and two CPD subjects were excluded because they had an IQ outside the range of 70-120. Additionally, two NPC with IQ scores above the 95-percentile were excluded to guarantee that NPC were matched to the BPD participants.MeasuresBorderline Personality Disorder Severity Index (BPDSI-VI) - The BPDSI is a semi-structured clinical interview assessing frequency and severity of borderline manifestations PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Bcm50ejwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+PFJl
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ADDIN EN.CITE.DATA [6].Brief Symptom Inventory (BSI) - The Brief Symptom Inventory is a brief psychological self-report inventory of general symptoms of psychopathology during the past week ADDIN EN.CITE <EndNote><Cite><Author>Derogatis</Author><Year>1993</Year><RecNum>94</RecNum><DisplayText>[8]</DisplayText><record><rec-number>94</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">94</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Derogatis, L.R.</author></authors></contributors><titles><title>BSI Brief Symptom Inventory: Administration, Scoring, and Procedure Manual</title></titles><edition>4th</edition><dates><year>1993</year></dates><pub-location>Minneapolis, MN</pub-location><publisher>National Computer Systems</publisher><urls></urls></record></Cite></EndNote>[8]. It is a short alternative for the Symptom Checklist-90-R from which it was developed. It contains 53 items divided over nine dimensions: somatization, obsession-compulsion, interpersonal sensitivity, depressive mood, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism. Answers are scored on a 5-point Likert scale, ranging from 0 (not at all) to 4 (extremely). Scores of the dimensions are calculated by summing the values for the items divided by the number of items within the subscales. The total score measures the level of symptomatology, which is the sum of the nine dimensions plus the four additional items divided by total number of items. The internal consistency showed a Cronbach’s α of 0.96 for the total instrument and ranged between 0.71 and 0.85 for its subscales ADDIN EN.CITE <EndNote><Cite><Author>De Beurs</Author><Year>2006</Year><RecNum>227</RecNum><DisplayText>[8, 11]</DisplayText><record><rec-number>227</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">227</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>De Beurs, E. </author><author>Zitman, F.G.</author></authors></contributors><titles><title>De Brief Symptom Inventory (BSI): De betrouwbaarheid en validiteit van een handzaam alternatief voor de SCL-90 [The Brief Symptom Inventory (BSI): The reliability and validity of a brief alternative of the SCL-90]</title><secondary-title>Maandblad Geestelijke Volksgezondheid</secondary-title></titles><periodical><full-title>Maandblad Geestelijke Volksgezondheid</full-title></periodical><pages>120-141</pages><volume>61</volume><dates><year>2006</year></dates><urls></urls></record></Cite><Cite><Author>Derogatis</Author><Year>1993</Year><RecNum>94</RecNum><record><rec-number>94</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">94</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Derogatis, L.R.</author></authors></contributors><titles><title>BSI Brief Symptom Inventory: Administration, Scoring, and Procedure Manual</title></titles><edition>4th</edition><dates><year>1993</year></dates><pub-location>Minneapolis, MN</pub-location><publisher>National Computer Systems</publisher><urls></urls></record></Cite></EndNote>[8, 11]. To distinguish patients from non-patients a cutoff score of 0.70 is suggested ADDIN EN.CITE <EndNote><Cite><Author>De Beurs</Author><Year>2004</Year><RecNum>228</RecNum><DisplayText>[12]</DisplayText><record><rec-number>228</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">228</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>De Beurs, E.</author></authors></contributors><titles><title>Handleiding bij de Brief Symptom Inventory (BSI)</title></titles><dates><year>2004</year></dates><pub-location>Leiden</pub-location><publisher>Pits Publishers</publisher><urls></urls></record></Cite></EndNote>[12].BPD Checklist - The BPD Checklist is a self-report questionnaire used to assess the burden of borderline symptoms as experienced during the last month ADDIN EN.CITE <EndNote><Cite><Author>Arntz</Author><Year>1995</Year><RecNum>101</RecNum><DisplayText>[9]</DisplayText><record><rec-number>101</rec-number><foreign-keys><key app="EN" db-id="a290pw5a65t2pded5p0ptspxrp22x525va2w">101</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Arntz, A.</author><author>Dreessen, L.</author></authors></contributors><titles><title>BPD-Klachtenlijst 47 [BPD Checklist]</title></titles><dates><year>1995</year></dates><pub-location>The Netherlands</pub-location><publisher>Maastricht University</publisher><urls></urls></record></Cite></EndNote>[9]. 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ADDIN EN.CITE.DATA [13]. IQ was estimated based on the optimized regression equation: 39.05 + (1.54*comprehension score) + (1.64*matrix reasoning score) + (1.48*similarities score) + (0.98*picture arrangement score). If the WAIS score was not available (borderline patients n = 11, non-patients n = 3 and control patients n = 1) an estimation of the IQ was made based on the education level, using the regression equation from our present sample per group; IQ borderline patients = 85.932 + (3.360*ISCED code), IQ non-patients = 85.996 + (3.659*ISCED code) and IQ control patients = 81.529 + (4.226*ISCED code). These regression equations explained respectively 22%, 31% and 36% of the variance in IQ. Level of education of both the Dutch and German educational systems were transformed into the International Standard Classification of Education (ISCED).Dissociation and Anxiety - Present state dissociative experiences were assessed using four items of the Dissociation-Tension-Scale PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdGlnbG1heXI8L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFy
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ADDIN EN.CITE.DATA [14], containing somatic dissociation such as changes in perception of one’s body, hearing, vision and pain. Additionally two items concerning the level of anxiety and the level of nervousness were added. Responses were indicated on a visual analogue scale, ranging from 0 not at all to 100 extreme. The dissociation score was the averaged across the four dissociation items. Internal consistencies of the dissociation score proved to be good in current sample, with a Cronbach’s α of 0.83 concerning dissociation before scanning and a Cronbach’s α of 0.88 concerning dissociation after scanning.Self-Assessment Manikin Scale - The pictures shown during the scanning session were qualitatively assessed for valence and arousal using the Self-Assessment Manikin Scale. The Self-Assessment Manikin Scale consists of a series of human-like figures to measures the affective reaction of a person to stimuli PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFkbGV5PC9BdXRob3I+PFllYXI+MTk5NDwvWWVhcj48
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ADDIN EN.CITE.DATA [15]. Intensity of valence and arousal were both rated on a 9-point scale, with for valence 1 being extremely unpleasant and 9 being extremely pleasant, and for arousal 1 being most calm and 9 being most aroused.MRI data acquisitionStructural and functional MRI data were acquired with 3 T scanners at three sites: in Maastricht on a Siemens Magnetom Allegra head-only scanner equipped with a birdcage headcoil (Siemens Medical Systems, Erlangen, Germany), in Freiburg on a Siemens tim-Trio Magnetom whole body scanner (Siemens Medical Systems, Erlangen, Germany) equipped with an 8-channel headcoil, and in Lübeck on a Philips Achiva whole body scanner equipped with an 8-channel headcoil (Philips Healthcare, Best, The Netherlands). The BPD patients from Heerlen were scanned in Maastricht and the BPD patients from Hamburg were scanned in Lübeck. In Maastricht 12 BPD, 9 NPC and 11 CCP were scanned, Freiburg scanned 13 BPD, 18 NPC and 6 CCP, finally 23 BPD, 12 NPC and 4 CCP were scanned in Lubeck.FMRI data preprocessingFMRI data preprocessing was carried out using BrainVoyager 2.8 (Brain Innovation, Maastricht, The Netherlands), NeuroElf (an MR imaging analysis toolbox, ) and custom routines in Matlab (Mathworks, Inc). The first two volumes were removed due to saturation effects. The following preprocessing steps were conducted: slice time correction with sinc interpolation, 3D motion correction for three translational and three rotational directions with trilinear/sinc interpolation, spatial smoothing with a 4 mm full-width-at-half-maximum isotropic Gaussian kernel, and removal of linear trend. Additionally, a temporal band-pass filter of 0.01 to 0.1 Hz was applied to reduce cardiac and respiratory noise. In order to further reduce the non-neuronal components of fMRI datasets, a component based method (CompCor) was applied to remove the significant principal components representing data artifacts from head motion, cerebrospinal fluid, and white matter PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZWh6YWRpPC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48
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ADDIN EN.CITE.DATA [16].Spatial normalization was conducted using a high-resolution anatomical datasets. Participants underwent a second fMRI session (data presented elsewhere), in which a second anatomical scan was acquired. In order to obtain a high resolution and high contrast anatomical scan, the individual anatomical datasets from the two fMRI sessions were averaged when possible. Anatomical datasets were corrected for inhomogeneity intensity and non-brain tissue was removed. Such individual anatomical datasets were used to co-register the single subject 4D functional datasets. All single subject datasets were normalized in Talairach space (1 × 1 × 1 mm; Talairach & Tournoux, 1988).Supplementary FiguresSupplementary Figure S1Fig. S1 Schematic overview of a single trial of the Emotion regulation paradigmDetailed description of the task is available elsewhere [van Zutphen et al., submitted], but for a schematic overview of a single trial see figure.Supplementary Figure S2Fig. S2 Amygdala seeds.A 5 mm sphere of the seeds used in the functional connectivity analyses were centered around the coordinates: ±22, -6, -14 (Talairach space).Supplementary Figure S3Fig. S3 Main effects of the amygdala resting-state functional connectivity in BPD and NPC (Panel A), and CPD (Panel B).The t-maps (whole brain FDR voxel-level corrected p < 0.05) depict average amygdala functional connectivity before and after the emotion regulation task. 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