Abstract Background Dissociative identity disorder (DID) is a disputed psychiatric disorder. Research findings and clinical observations suggest that DID involves an authentic mental disorder related to factors such as traumatization and disrupted attachment. A competing view indicates that DID is due to fantasy proneness, suggestibility, suggestion, and role-playing. Here we examine whether dissociative identity state-dependent psychobiological features in DID can be induced in high or low fantasy prone individuals by instructed and motivated role-playing, and suggestion. Methodology/Principal Findings DID patients, high fantasy prone and low fantasy prone controls were studied in two different types of identity states (neutral and trauma-related) in an autobiographical memory script-driven (neutral or trauma-related) imagery paradigm. The controls were instructed to enact the two DID identity states. Twenty-nine subjects participated in the study: 11 patients with DID, 10 high fantasy prone DID simulating controls, and 8 low fantasy prone DID simulating controls. Autonomic and subjective reactions were obtained. Differences in psychophysiological and neural activation patterns were found between the DID patients and both high and low fantasy prone controls. That is, the identity states in DID were not convincingly enacted by DID simulating controls. Thus, important differences regarding regional cerebral bloodflow and psychophysiological responses for different types of identity states in patients with DID were upheld after controlling for DID simulation. Conclusions/Significance The findings are at odds with the idea that differences among different types of dissociative identity states in DID can be explained by high fantasy proneness, motivated role-enactment, and suggestion. They indicate that DID does not have a sociocultural (e.g., iatrogenic) origin.

Citation: Simone Reinders AAT, Willemsen ATM, Vos HPJ, den Boer JA, Nijenhuis ERS (2012) Fact or Factitious? A Psychobiological Study of Authentic and Simulated Dissociative Identity States. PLoS ONE 7(6): e39279. https://doi.org/10.1371/journal.pone.0039279 Editor: Jerson Laks, Federal University of Rio de Janeiro, Brazil Received: March 5, 2012; Accepted: May 16, 2012; Published: June 29, 2012 Copyright: © 2012 Reinders et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: AATSR is supported by the Netherlands Organization for Scientific Research (www.nwo.nl), NWO-VENI grant no. 451-07-009. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist.

Introduction Despite its inclusion in the Diagnostic Manual for Mental Disorders [1], the genuineness of dissociative identity disorder (DID) continues to be disputed. Supporters of the diametrically opposed trauma-related and non-trauma-related views have been engaged since decades in a passionate debate regarding its validity as a mental disorder, and whether it is related to traumatization or to fantasy proneness, suggestibility, suggestion, and simulation [2]–[10]. The non-trauma-related position [2], [3], [7], [11]–[13], also referred to as the sociocognitive model of DID [14]–[16], holds that DID is a simulation caused by high suggestibility and/or fantasy proneness [17]–[21], suggestive psychotherapy and other suggestive sociocultural influences (e.g., the media and/or the church). According to this model, “[t]he rules for enacting the [DID] role […] are as follows: (a) Behave as if you are two (or more) separate people who inhabit the same body. (b) Act as if the you I have been addressing thus far is one of those people and as if the you I have been talking to is unaware of the other coinhabitants. (c) When I provide a signal for contacting another coinhabitant, act as though you are another person. To the extent that patients behave in terms of these rules, the “classic” symptoms [of DID] follow by implication and do not have to be taught through direct instruction or further suggestion”, Spanos (p.239 [15]). Fantasy proneness and suggestibility are highly correlated [18], [22]–[25], and dissociative symptoms were found to be correlated with fantasy proneness, heightened suggestibility, and susceptibility to pseudomemories [11], [26]. To date, the position that DID is caused by sociocultural factors and personal features such as fantasy proneness has not been tested in studies involving DID patients, and evidence that the complex phenomenology and psychobiology of DID can be created and sustained over time by these factors is lacking [27]–[30]. Despite this lack of empirical support, the sociocognitive and fantasy based model of DID is influential in contemporary psychiatry and there have been proposals to prevent the inclusion of DID in the DSM-V [31]. The trauma-related perspective entails that DID is related to a combination of factors that include chronic emotional neglect and emotional, physical, and/or sexual abuse from early childhood, insufficient integrative capacity, attachment disorder, and lack of affect-regulation by caretakers [27], [32]–[35]. In this view DID is thought to be at the far end of the spectrum of trauma-related psychiatric disorders, i.e. being a severe form of post-traumatic stress disorder (PTSD) [33], [36]. Holders of the trauma-related view acknowledge that: some features of dissociative identity states can be influenced by sociocultural factors [33], that false positive cases of DID have evolved in a treatment setting, and that some psychiatric patients imitate DID [37]. However, they also note that there are differences between authentic and imitated DID and that there is no evidence that DID can (sub-)consciously be created by sociocultural factors [27]. Furthermore, even if DID symptoms can be created iatrogenically or enacted [14] this does not mean that genuine trauma-related DID does not exist [38]. According to the DSM-IV [1], DID is characterized by, among others, the presence of two or more distinct `identities’ or `personality states’. Different proposed labels include `different emotional states’, `alters’, `dissociative parts of the personality’ [33], and `dissociative identity states.’ Following previously used descriptions and terminology [39], [40] different types of dissociative identity states are indicated here as neutral identity states (NIS) and trauma-related identity states (TIS). These indicators are derived from the terms ‘apparently normal part of the personality (ANP)’ and ‘emotional part of the personality (EP)’ respectively, which are used in the theory of structural dissociation [33], [41]. This theory defines dissociation as a division of personality into different types of subsystems, each with their own first-person perspective, that is, their own point of view as to who they are, what the world is like, and how they relate to that world [42]. As NIS DID patients concentrate on functioning in daily life, commonly try to hide their pathology, and have not sufficiently integrated (e.g., have partial or complete amnesia) traumatic memories. That is, NIS fails to relate the trauma-related nature to its self [39]. In contrast, TIS does have conscious access to these memories, recalls them as personal experiences and is bodily and emotionally affected by them. That is, as TIS the patients are fixated in traumatic memories and engage in defensive actions such as freeze and flight, when they are or feel threatened [41], [43], thereby activating fast subcortical response routes in the brain [40], [44]. TIS who engage in active kinds of physical defence (e.g., freeze, flight, fight) would involve dominance of the sympathetic nervous system, whereas those who engage in total submission (i.e.,playing dead) would be primarily mediated by the dorsal vagal branch of the parasympathetic nervous system [45]. Proponents of the sociocognitive view have argued that the different patterns of subjective, psychophysiological, and neural activity for NIS and TIS in response to a trauma-memory script that Reinders et al. [39], [40] documented, might be due to fantasy proneness, suggestion and role-playing, and that they do not prove a traumagenic origin of DID. Obtaining independent proof of childhood traumatization in adulthood is most difficult. However, the claim that the previously reported results constitute effects of fantasy proneness, suggestion, and role-playing is open to test. Thus, the present study involves a psychobiological comparison between NIS and TIS engaging in active kinds of physical defence in DID patients (i.e., the DID identity states from Reinders et al. [39], [40]), and simulated NIS and TIS in high and low fantasy prone mentally healthy women who do not report a trauma history and who are instructed and motivated to role-play these different identity states (i.e., simulated identity states). The a priori hypotheses of the current study were: (i) important previously found psychophysiological and neurobiological differences between NIS and TIS engaging in active kinds of physical defence in DID patients [39], [40] are upheld when controlling for fantasy proneness, suggestion, and instructed and motivated role-playing, and (ii) the upheld psychophysiological and neurobiological differences for NIS and TIS in DID patients include higher sympathetic nervous system activation (e.g. higher heart rate and systolic bloodpressure) and subcortical activity (e.g. the amygdala and caudate nucleus) for TIS in DID, and (iii) hyperactivation of the cortical multimodal posterior association areas (e.g. the intraparietal sulcus and (pre-)cuneus) for NIS in DID when listening to personal trauma scripts.

Methods Participants Controls. Mentally healthy females were recruited by local newspaper advertisements. Respondents were sent a letter in which the study was explained and in which they were invited to complete three questionnaires: (i) the Traumatic Experiences Checklist (TEC) [67], a self-report questionnaire assessing potentially traumatizing events such as physical abuse and emotional neglect, (ii) the Somatoform Dissociation Questionnaire (SDQ-20 [68]–[70], a self-report questionnaire evaluating the severity of somatoform dissociative symptoms, e.g., analgesia, anesthesia, motor inhibitions), and (iii) the Creative Experiences Questionnaire (CEQ) [18] which measures fantasy proneness. Exclusion criteria were the presence of medical, neurological or psychiatric problems in the past or the present, the use of psychotropic medication 15 days prior to examination, participation in a positron emission tomography (PET) or other study that involved administration of radiation in the year prior to this study, and pregnancy. A total of 18 healthy controls participated in the study, which was approved by the Medical Ethical Committee of the University Medical Center Groningen. After inclusion, written and oral information on dissociative identity states (i.e. NIS and TIS) in DID and instructions on how to simulate these dissociative identity states was given to the controls. It was checked whether the controls understood this information. A template for training themselves in switching between the simulated identity states was provided. Controls were then questioned about how they constructed the two identity states, whether they encountered difficulties and if so, they were given support to improve their roles as NIS and TIS. To help the controls simulate NIS and TIS, they were asked to recall two experiences they had had earlier in their life, an emotionally neutral experience and an emotionally painful experience. Controls were asked to provide their most painful memory to serve as an analogue for the patients’ personal trauma memories, as well as a neutral personal episodic memory. Controls were subsequently instructed how to write the autobiographical analogue neutral and “trauma” memory scripts. For the experiment they had to train themselves in being in a neutral state, the NIS who is unresponsive or under-responsive to the painful experience, and in being in a state in which they re-experience the painful memory, the TIS. The consecutive and final check on the capability to simulate the two different dissociative identity states consisted in checking whether their description of their neutral and painful experiences (that was to be casted in an audiotape recording) met the instructions on how to enact a DID patient. In the two or more weeks preceding the PET scans, candidate control subjects practiced simulating NIS and TIS, as well as alternating between NIS and TIS using detailed role instructions. One of the investigators (H.V.) contacted the candidates per telephone during this preparatory phase to ensure that they followed the instructions and to offer further suggestions for optimizing their role performance. One candidate felt unable to simulate the roles satisfactorily, and was therefore excluded. Prior to the actual PET scanning, H.V. checked if the candidates experienced and judged that they were able to simulate the roles of NIS and TIS. During the actual scanning, he checked if they engaged in the requested simulations, and immediately after the role performances, he checked if the controls generally felt they had simulated the roles of NIS and TIS effectively. All controls passed these various checks. In addition, immediately after each text condition, H.V. administered a detailed questionnaire that inquired after the controls’ subjective sensorimotor and emotional experiences during their role performance. This questionnaire was identical to the one in the patient study [39], [40], which was administered by the patients’ therapist, and debriefed six subjective emotional experiences (fear, sorrow, sadness, anger, shame and disgust) and ten sensorimotor experiences (visual, kinesthetic, auditory, olfactory + gustatory reactions, pain, physical numbness, body stiffening, paralysis and restlessness) were debriefed. In addition, the presence of the identity state under investigation and the interference among identity states were also debriefed. Using this questionnaire, H.V. or the patients’ therapist could structurally evaluate if the intended NIS or TIS had been present during the experimental condition. Statistical analyses of the simulation performance in terms of their subjective experiences, i.e. the subjective sensorimotor perception and emotional response, during the scanning by the two control groups are provided in Supporting Information S2. As we did not have CEQ values for the patients (see also Supporting Information S1) we could not control for fantasy proneness by including a covariate. Therefore, the controls were divided into two groups based on their CEQ scores resulting in a high fantasy prone group (n = 10, age 38.2 (SD 10.9), TEC 0.7 (SD 1.3), SDQ-20 22 (SD 2.4)) with CEQ 13.7 (SD 3.2) and a low fantasy prone group (n = 8, age 42.5 (SD 10.1), TEC 0.4 (SD 0.5), SDQ-20 20.9 (SD 1.5)), with CEQ 3.9 (SD 1.6). A CEQ cut-off for high fantasy proneness of 10 was used, which the developers of the CEQ recommended for the current sample [71]. Patients A detailed description of the DID patients can be found elsewhere [39], [40]. In short: Eleven patients (all female, age 41.0, SD 6.1) participated: (i) whose treatment had progressed to Phase II [72], which involves therapeutic exposure to trauma-related memories, (ii) who met criteria for DID, as operationalized in the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D [73]), and (iii) had at least one TIS and one NIS that they could activate on demand [33] and (iv) the involved TIS had displayed signs of sympathetic nervous system dominance under perceived threat in clinical situations. To establish the CEQ values in DID patients an independent and representative sample of DID patients (n = 42) completed the CEQ. Details regarding this substudy can be found in the Supporting Information S1. Stimulus Scripts During scanning, patients and controls listened to descriptions of the neutral episodic memories and memories of traumatizing or most painful events that only TIS experienced as a personal memory [74]. These memories were cast, prior to the PET session, by the therapist or one of the principal investigators (H.V.) in terms of stimulus descriptions, and were subsequently audio-taped in a neutral tone of voice as 120 second scripts for playback during the PET investigation. PET Procedure The PET (Siemens/CTI ECAT HR+) procedure for the controls was close to identical to the patients [39], [40]. In contrast to patients the controls did not habituate to the PET environment prior to the investigation as anxiety levels were expected to be low. Approximately two hours prior to the PET investigation the continuous ECG registration was started, obtaining the five frequency and time domain variables [75], [76]. No urine samples were obtained for the control groups, both medication and drugs use were verbally debriefed according to standard control research practice. For the controls one extra set of the four conditions was added to increase statistical power. The scanning sequence was therefore NISn, NISt, TISn, TISt, TISn, TISt, NISn, NISt, TISn, TISt, NISn and NISt. The last minor character (n or t) denotes the content of the memory script (MS: neutral or trauma-related). For patient comfort considerations, i.e. minimizing the number of identity state switches, a fixed condition order was used, which was also used for the controls to minimize methodological differences. Immediately following the end of each script, blood pressure (systolic and diastolic) and discrete heart rate frequency were measured and the six subjective emotional and ten sensorimotor experiences were debriefed. Finally, the presence of the identity state under investigation and the interference among identity states were also debriefed. Image Acquisition and Data Processing Data acquisition, reconstruction, attenuation correction, spatial transformation, spatial smoothing (isotropic Gaussian kernel of 12 mm) and global normalization were performed as usual [39], [40], [77]. SPM5 (www.fil.ion.ucl.ac.uk/spm) was used for spatial transformation to the MNI template (using heavy regularization) [78], [79] and statistical analysis [80] of both patient and control data. Data Analysis: Autonomic and Subjective Reactions Statistical analysis, missing value analysis and principal components (PC) analysis were performed with SPSS-PC 15.0 (2006) in an identical manner as was done for the patient data [39], [40]. Results with p<0.05 are reported as significant. Within SPSS two two-by-two-by-two factorial design were defined with the first factor Group, consisting of the levels DID and the high fantasy prone controls or the low fantasy prone controls, a second factor identity state, consisting of the levels NIS and TIS, and the third factor was MS, consisting of the levels neutral and trauma-related. For one high fantasy prone and one low fantasy prone subject heart rate variability (HRV) data could not be obtained. In addition, the data, including the PET data, from two NISt conditions was removed as the control subjects reported not to be able to maintain as a NIS. One TISn condition was removed from the low fantasy prone data as the subject reported not to be able to maintain a TIS. Bonferoni correction to correct for multiple testing was applied. Data Analysis: PET-data The patient PET data included in the current study is identical to the data as included and described in our previous publications [39], [40]. This study assessed various effects, e.g., main effects and simple subtraction analyses (within and between identity state) within the DID group using SPM99. This data was re-analyzed in SPM5 and is referred to as the “within DID only” analyses. From the 10 high fantasy prone healthy controls the PET data of one subject was lost due to storage failure at the PET center. The data of the three groups was statistically analyzed in SPM5 in a three-by-two-by-two factorial design [81]–[84]. The general linear model (GLM) consisted of the three factor main effects, the four conditions and a group by condition interaction. In addition, the subjective reactions and the autonomic reactions were included as group specific covariates of interest after PC analysis [39], [40]. The variance in the subjective ratings could be described with the first two, six, and five PC for the DID, high and low fantasy prone groups respectively, explaining 64%, 68%, and 72% of the variance. The variance in the autonomic reactions could be described with the first three PC for each of the DID, high and low fantasy prone groups, explaining 85%, 82%, and 87% of the variance respectively. Finally, the global cerebral blood flow (CBF) was included as a nuisance covariate (AnCova by subject). Hypothesis Testing Previously reported significant findings were tested using a between group subtraction of the within group results (e.g. DID(TISt-NISt)-Control(TISt-NISt)). Commonalities in brain activation between patients and controls were tested using global null conjunction analyses [83]. Statistical Inference and Reporting Our a priori hypothesis was that earlier findings would still hold after the correction for non-trauma-related factors. Both whole brain and a priori region of interest (ROI) multiple comparisons correction were performed on the basis of false discovery rate statistics [85]. Statistical parametric maps were thresholded using an uncorrected threshold of p<0.001 [40], [86] and explored for a priori hypothesized brain areas. If an a priori hypothesized brain area did not survive whole brain multiple comparison correction, multiple comparisons correction was performed within the a priori region of interest (ROI). For subcortical located ROI and ROI in the cerebellum a sphere with a volume of 3054 mm3 [87] was used. For larger cortical a priori hypothesised ROI a sphere with a volume of 6108 mm3 was used. Note: in line with previously used statistical thresholds [40] voxels surviving significant levels only uncorrected for multiple testing for the whole brain, i.e. p<0.001 [40], [86] were reported as well, but for comparison purposes only. Only clusters larger than eight voxels are reported taking into account the spatial resolution of the PET camera. In contrast to the earlier publication [40], this time all peak voxels are reported for a more accurate comparison between groups. The coordinates were converted from MNI space to Talairach space [88] to be defined in Brodmann areas (BA) using both the Talairach atlas [79] and Deamon [89], [90]. Activations in sulci was defined using Brain Tutor [91]. The location was anatomically compared to and described using a second brain atlas [92].

Acknowledgments The authors are greatly indebted to all the participants: thank you for participating. They also would like to thank Margo Jongsma for her assistance and participant recruitment. Jaap Haaksma is thanked for the HRV data collection and Marc van Ekeren for help during data collection and pilot analyses. Finally, Borden Armstrong is thanked for psychophysiological data-analysis support and proof reading.

Author Contributions Conceived and designed the experiments: AATSR ATMW JAB ERSN. Performed the experiments: AATSR HPJV. Analyzed the data: AATSR ATMW. Wrote the paper: AATSR ATMW HPJV JAB ERSN.