Table 1.

Overview of experimental studies on dissociation in borderline personality disorder, identified by our literature search as published between 01/2017 and 12/2020

Authors, year of publication	Sample (groups, sample size), gender	Psychotropic medication status	Comorbidities and trauma history in the patient sample	Method and experimental design	Measures of dissociation (trait/state, time)	Key findings concerning dissociation
Neuroimaging studies on dissociation
Baczkowski et al., (2017)	• Groups: - BPD (n = 48) - Non-patients (NPC, n = 48) - Cluster-C PD (CPD, n = 31) • Gender: Female	Most patients received antidepressants, and further received antipsychotics, hypnotics, or mood stabilizers.	All patients reported a history of childhood trauma (including emotional, physical and sexual abuse, emotional/physical neglect). Comorbidities predominantly with major depressive disorder (MDD) and substance abuse.	Resting state (RS) fMRI was acquired to investigate effects of effortful emotion regulation on amygdala functional connectivity in BPD.	Self-reported dissociation (DES) assessed prior to and immediately after scanning.	Unlike controls, BPD patients did not show an increase of amygdala resting-state functional connectivity with medial, dorsolateral, ventrolateral PFC and superior temporal gyrus after effortful emotion regulation. Dissociation did not correlate with change of amygdala RSFC in BPD.
Krause-Utz et al., (2018)	• Groups: - BPD patients with acute dissociation (dissociation script, BPDd, n = 17) - Patients exposed to neutral script (BPDn, n = 12) - HC (n = 18) • Gender: Female	Free of psychotropic medication for at least 4 weeks prior to study.	All patients reported at least one type of severe to extreme childhood trauma. 5 patients in the BPDn group and 7 in the BPDd group met criteria for current PTSD. Comorbidity with current (other) anxiety and eating disorders. Lifetime psychotic disorder, bipolar-I disorder, mental retardation, and substance abuse 6 months prior to scan were excluded.	fMRI to measure changes in BOLD signal, combining script-driven imagery (experimentally induces dissociation) with a subsequent emotional working memory task (EWMT, with socio-emotional distractors).	Dissociation was induced in 17 patients, while 12 patients and 18 HC were exposed to a personalized neutral script. Self-reported trait dissociation (DES) and state dissociation at baseline, after script and after EWMT.	BPDd showed WM deficits, reduced bilateral amygdala activity (across conditions) and reduced left cuneus, lingual gyrus, and posterior cingulate activity (during negative distractors) compared to BPDn. Inferior frontal gyrus activity was higher in both BPD groups than in HC. BPDd showed a stronger coupling of amygdala with right superior/ middle temporal gyrus, right middle occipital gyrus, left inferior parietal lobule, and left claustrum than BPDn and HC.
Popkirov et al., (2019)	• Groups: - BPD (n = 26) - HC (n = 26) • Gender: Female	Some patients received antidepressants (n = 11), antipsychotics (n = 6), anticonvulsants (n = 3) and other psychoactive drugs (n = 2).	All patients reported a history of childhood trauma (including emotional, physical and sexual abuse, neglect). Some patients met criteria for depression (n = 17), phobic/anxiety disorder (n = 3), PTSD (n = 5), or substance abuse (n = 6).	EEG recordings before (pre) and after (post) mood induction using aversive IAPS pictures (50 negative/50 neutral) to measure frontal electroencephalographic asymmetry (FEA) as a trait and/or state parameter of emotion regulation.	Self-reported dissociation (DES).	Changes in FEA in BPD and healthy controls while negative pictures were presented (slight but significant shift from left- to right-sided asymmetry over prefrontal electrodes). Baseline FEA correlated significantly with childhood trauma severity (CTQ) and trait dissociation (DES) in patients with BPD.
Zaehringer et al., (2019)	• Group: BPD (n = 24) • Gender: Female	All participants were on stable medication, including SSRI (n = 3), SNRI (n = 4), Tricyclic (n = 3) other antidepressants (n = 3), neuroleptics (n = 5) and anticonvulsants (n = 2); 10 patients were un-medicated.	Some patients met criteria for current MDD (n = 6), lifetime MDD (n = 22), PTSD (n = 6). Other comorbidities were dysthymia, double depression, panic disorder, social phobia disorder, specific phobia, and eating disorder. Alcohol or substance abuse 6 months prior to scan, lifetime psychotic disorder, bipolar affective disorder and mental retardation were excluded.	Real-time fMRI-based neurofeedback training consisting of four sessions in which participants viewed aversive pictures and received feedback from a thermometer displaying amygdala BOLD signals during an Emotional working memory task and a Backward Masking Task.	Self-reported dissociation (DSS).	After training, participants reported a decrease of BPD symptoms and showed a decrease in emotion-modulated startle to negative pictures. A reduction of dissociation was observed which did not reach significance.
Psychophysiological studies on dissociation
Bischescu-Burian et al., (2017)	BPD (n = 13), BPD with high peritraumatic dissociation (PD, n = 15) and healthy controls (HC, n = 15), all female.	Free of psychotropic medication for at least 1 week prior to physiological assessment.	Patients reported childhood trauma. Some patients met criteria for PTSD or dissociative disorder. Other comorbidities were affective disorders, anxiety disorder, and eating disorders. Exclusion of schizophrenia and substance abuse.	Participants were exposed to personalized script-driven imagery (consisting of 3 script presentations) with traumatic and everyday neutral events. Emotional and psychophysiological reactions (heart rate (HR) and skin conductance (SCR)) were assessed during the experiment.	Self-reported trait dissociation (DES) and peritraumatic dissociation experiences (PDEQ).	BPD patients with high PD showed a significant HR decline during imagery of traumatic events (versus increased HR in the other groups); HR responses were predicted by PD, but not by measures of state or trait dissociation. Groups did not differ in SCR.
Koenig et al., (2018)	Adolescents (13–19 years) with BPD (n = 30), healthy controls (n = 34) and psychiatric clinical controls (CC, n = 53) participated in the trial, all female.	Some of the BPD and CC patients received medication including anti-depressives (n = 6), stimulants (n = 2), neuroleptics, (n = 3) and other (n = 4).	BPD and CC patients reported sexual (n = 13) and physical abuse (n = 15). The BPD and CC patients presented with a range of axis I and axis II disorders. Exclusion criteria included current drug or alcohol dependence, lifetime schizophrenia, schizoaffective disorder, bipolar disorder, pervasive developmental disorder or any neurological disease.	Participants listened to startle-probes (78-dB, 1000 ms, 1000 Hz) while heart rate (HR) and skin conductance (SCR) were continuously recorded.	Self-report dissociation scale for adolescents (DES-A).	HR significantly differed between the CC and BPD groups. HR was also associated with number of BPD diagnostic criteria and with symptoms of dissociation. Delayed HR habituation across probes was associated with greater BPD symptom severity.
Krause-Utz et al., (2018)	BPD (BPD, n = 37), BPD with comorbid PTSD (BPD + PTSD, n = 20) and healthy controls (n = 27), all female.	n = 23 patients (BPD: n = 15; BPD + PTSD: n = 8) received psychotropic medication, including SSRI, tricyclic antidepressants, and antipsychotic medication.	All patients reported childhood trauma. Some patients had comorbid MDD (n = 21), or anxiety disorders (n = 13). Exclusion criteria for patients were lifetime history of bipolar disorder, psychotic disorder, acute life-threatening suicidal crisis, mental deficiency, and severe organic disorder.	Participants performed a cognitive reappraisal (emotion regulation) task with neutral, positive, and negative images. Participants were instructed to either attend these pictures or to down-regulate their upcoming emotions. Acute arousal, wellbeing, dissociation, and electrocardiogram data were assessed.	Self-reported dissociation (Dissociative Tension Scale, DSS4).	Independent of instruction and picture valence, both patient groups reported higher arousal, lower wellbeing, and more dissociation than HC. BPD + PTSD showed significantly lower HF-HRV than the other groups. In BPD + PTSD, higher state dissociation at baseline predicted higher HF-HRV during down-regulating vs. attending negative pictures.
Body ownership
Löffler et al., (2020)	Patients with acute BPD (BPD-C, n = 26), remitted BPD (BPD-R, n = 22) and healthy controls (HC, n = 20), all female.	Apart from selective serotonin reuptake inhibitors, patients were free of psychotropic medication.	Exclusion of lifetime bipolar-I disorder or schizophrenia, mental retardation, and substance dependency disorder within the last year.	Body ownership for 25 body areas, relations to dissociation and other relevant BPD markers were assessed. Participants were asked to close their eyes, sit relaxed, and rate the state degree of belongingness for a given body area. All 25 body areas were read out loud. Participants rated each item verbally.	Self-reported trait (German DES)	Patients with acute BPD showed reduced body ownership experiences compared to HC, while they did not differ from those with BPD in remission. In acute BPD, reduced body ownership was significantly related to dissociation when controlling for other BPD core features.
Pain processing
Chung et al., (2020)	Patients with acute BPD (BPD-C, n = 25), remitted BPD (BPD-R, n = 20) and healthy controls (n = 24), all female.	n = 3 BPD-C patients and n = 1 BPD-R patient received anti-depressant medication (SSRIs).	n = 9 patients in the BPD-C group met criteria for current PTSD, and 10 patients from the BPD-C and 5 from the BPD-R group met criteria for lifetime PTSD. Comorbidity with current and lifetime depression, current anxiety disorders, and phobias was evident. Lifetime diagnosis of schizophrenia, bipolar-I disorder, substance dependence 2 years prior to study or current substance abuse were excluded.	Script-driven imagery to induce dissociation: participants were exposed to a personalized dissociation-inducing script (vs. to a neutral script). Warm perception thresholds (WPT) and heat pain thresholds (HPT) were assessed.	Self-reported dissociation on the DSS4, assessed prior to and after the script.	Compared to HC, both BPD-C and BPD-R showed enhanced dissociation along with pain hyposensitivity (higher HPT levels) in the stress condition. In BPD-C (but not in BPD-R), a significant association between dissociation proneness and hyposensitivity to pain (suggesting analgesia) was observed.
Defrin et al., (2019)	BPD (n = 22) and HC (n = 33), all female.	n = 18 BPD patients received psychotropic medication (antidepressants: n = 15; anxiolytics: n = 11).	Comorbid anxiety disorders (n = 8), MDD (n = 7), attention deficit hyperactivity disorder (n = 3), eating disorder (n = 3) or PTSD (n = 2). Exclusion of neurological and systemic diseases, or lifetime psychosis substance abuse.	Pain modulation measurements of warmth sensation threshold (WST) and heat pain threshold (HPT), conditioned pain modulation (CPM) and temporal summation of heat pain (TSP).	Self-reported Dissociation (DES).	Patients with BPD showed higher WST and HPT, suggesting generalized hyposensitivity and more efficient pain inhibition capabilities, compared with HC. No significant correlation between HPT and dissociation in BPD.

BOLD, blood oxygen level-dependent; BPD, borderline personality disorder; BPD-C, acute BPD; BPD-R, remitted BPD; CPM, conditioned pain modulation; CTQ, Childhood Trauma Questionnaire; DES, dissociation experience scale; DES-A, dissociation experience scale adolescent; DSS21, Dissociation Stress Scale 21 items version; DSS4, Dissociation Tension Scale 4 items version; EWMT, emotional working memory task; FEA, frontal electroencephalographic asymmetry; fMRI, functional magnetic resonance imaging; HC, healthy controls; HPT, heat pain threshold; HRV, heart rate variability; IAPS, international affective picture system; MDD, major depressive disorder; PDEQ, Peritraumatic Dissociation Experiences Questionnaire; PD, personality disorder; PFC, prefrontal cortex; PTSD, post-traumatic stress disorder; RSFC, resting-state functional connectivity; SSRI, selective serotonin reuptake inhibitors; TSP, temporal summation of heat pain