Dissociative Subtype Research Articles

Unravelling psychiatric heterogeneity and predicting suicide attempts in women with trauma-related dissociation using artificial intelligence

ABSTRACT Background: Suicide is a leading cause of death, and rates of attempted suicide have increased during the COVID-19 pandemic. The under-diagnosed psychiatric phenotype of dissociation is associated with elevated suicidal self-injury; however, it has largely been left out of attempts to predict and prevent suicide. Objective: We designed an artificial intelligence approach to identify dissociative patients and predict prior suicide attempts in an unbiased, data-driven manner. Method: Participants were 30 controls and 93 treatment-seeking female patients with posttraumatic stress disorder (PTSD) and various levels of dissociation, including some with the PTSD dissociative subtype and some with dissociative identity disorder (DID). Results: Unsupervised learning models identified patients along a spectrum of dissociation. Moreover, supervised learning models accurately predicted prior suicide attempts with an F1 score up to 0.83. DID had the highest risk of prior suicide attempts, and distinct subtypes of dissociation predicted suicide attempts in PTSD and DID. Conclusions: These findings expand our understanding of the dissociative phenotype and underscore the urgent need to assess for dissociation to identify individuals at high-risk of suicidal self-injury.

Women with PTSD and Substance Use Disorders in a Research Treatment Study: A Comparison of those with and without the Dissociative Subtype of PTSD

ABSTRACT Significant differences in clinical features have been reported in women with substance use disorders (SUDs) between those with the dissociative subtype of posttraumatic stress disorder (D-PTSD) compared to those without, namely more severe trauma histories, PTSD symptoms, and general psychopathology. This presentation reports on a group of 88 women with PTSD and SUD taking part in a research treatment study. All women were assessed using the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and were categorized into those with (n = 23, 26%) and without (n = 65, 74%) D-PTSD. Assessments for SUDs were via the Multi-International Neuropsychiatric Inventory, Seventh Version (MINI-7). Compared to those without D-PTSD, those with D-PTSD had significantly higher CAPS-5 scores (50.5 ± 9.9 v. 39.6 ± 8.8), greater number of PTSD symptoms (16.4 ± 2.6 v. 14.2 ± 2.4), more alcohol use disorder (AUD) (65.2% v. 30.8%), and more non-cocaine stimulant use disorder (34.8% v. 12.3%). No significant differences were found for other SUDs. These women with SUDs and D-PTSD have higher degrees of PTSD severity as well as unique clinical presentations. Future research is needed to explore the significance of these findings for clinical assessment and treatment.

The Vestibulocerebellum and the Shattered Self: a Resting-State Functional Connectivity Study in Posttraumatic Stress Disorder and Its Dissociative Subtype

The flocculus is a region of the vestibulocerebellum dedicated to the coordination of neck, head, and eye movements for optimal posture, balance, and orienting responses. Despite growing evidence of vestibular and oculomotor impairments in the aftermath of traumatic stress, little is known about the effects of chronic psychological trauma on vestibulocerebellar functioning. Here, we investigated alterations in functional connectivity of the flocculus at rest among individuals with post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS) as compared to healthy controls. Forty-four healthy controls, 57 PTSD, and 32 PTSD + DS underwent 6-min resting-state MRI scans. Seed-based functional connectivity analyses using the right and left flocculi as seeds were performed. These analyses revealed that, as compared to controls, PTSD and PTSD + DS showed decreased resting-state functional connectivity of the left flocculus with cortical regions involved in bodily self-consciousness, including the temporo-parietal junction, the supramarginal and angular gyri, and the superior parietal lobule. Moreover, as compared to controls, the PTSD + DS group showed decreased functional connectivity of the left flocculus with the medial prefrontal cortex, the precuneus, and the mid/posterior cingulum, key regions of the default mode network. Critically, when comparing PTSD + DS to PTSD, we observed increased functional connectivity of the right flocculus with the right anterior hippocampus, a region affected frequently by early life trauma. Taken together, our findings point toward the crucial role of the flocculus in the neurocircuitry underlying a coherent and embodied self, which can be compromised in PTSD and PTSD + DS.

The PTSD Symptom Presentation and the Effect of Polytrauma on PTSD Symptom Clusters Among Young People Who Have Experienced Commercial Sexual Exploitation and Trafficking.

The purpose of this study was to describe the PTSD symptom presentation (including dissociative symptoms) of PTSD using the Diagnostic and Statistical Manual of Mental Disorders 5 th Edition diagnostic criteria and explore associations between the symptom severity for each of the four PTSD symptom clusters and polytrauma, defined as multiple exposures to different categories of potentially traumatic events. This is a secondary analysis of cross-sectional program evaluation data among 95 young people (aged 11-19) at therapy initiation in a southeastern state in the U.S. We used descriptive statistics and multivariable linear regression to test study objectives. Eighty-one respondents (90.0%) experienced a potentially traumatic event in ≥ 2 trauma categories, in addition to experiencing CSE/T. Approximately two-thirds of respondents experienced clinically significant PTSD symptoms for each symptom cluster. Of the 31 young people who met full criteria for PTSD, 9 met criteria for the standard PTSD diagnosis, while 22 met criteria for the dissociative subtype of PTSD. On average, experiencing additional trauma categories was associated with substantively higher PTSD symptom cluster scores for each cluster. These findings support the need for a comprehensive assessment of trauma symptoms that includes cluster-specific PTSD symptoms. They also underscore the need to assess the full breadth and chronicity of trauma experiences to guide treatment planning and delivery, targeting specific domains of trauma impact. These findings can also inform the tailoring and adaptation of evidence-based interventions and strategies to better meet the needs of young people who have experienced CSE/T.

Prevalence of the dissociative subtype of post-traumatic stress disorder: a systematic review and meta-analysis.

The dissociative subtype of post-traumatic stress disorder (PTSD-DS) was introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and is characterised by symptoms of either depersonalisation or derealisation, in addition to a diagnosis of post-traumatic stress disorder (PTSD). This systematic review and meta-analysis sought to estimate the point prevalence of current PTSD-DS, and the extent to which method of assessment, demographic and trauma variables moderate this estimate, across different methods of prevalence estimation. Studies included were identified by searching MEDLINE (EBSCO), PsycInfo, CINAHL, Academic Search Complete and PTSDpubs, yielding 49 studies that met the inclusion criteria (N = 8214 participants). A random-effects meta-analysis estimated the prevalence of PTSD-DS as 38.1% (95% CI 31.5-45.0%) across all samples, 45.5% (95% CI 37.7-53.4%) across all diagnosis-based and clinical cut-off samples, 22.8% (95% CI 14.8-32.0%) across all latent class analysis (LCA) and latent profile analysis (LPA) samples and 48.1% (95% CI 35.0-61.3%) across samples which strictly used the DSM-5 PTSD criteria; all as a proportion of those already with a diagnosis of PTSD. All results were characterised by high levels of heterogeneity, limiting generalisability. Moderator analyses mostly failed to identify sources of heterogeneity. PTSD-DS was more prevalent in children compared to adults, and in diagnosis-based and clinical cut-off samples compared to LCA and LPA samples. Risk of bias was not significantly related to prevalence estimates. The implications of these results are discussed further.

A Network Analysis Study Investigating Posttraumatic Stress Disorder and Dissociation Comorbidity in a UK Armed Forces Veteran Sample

IntroductionAn established body of literature has identified that PTSD and dissociation are comorbid. Furthermore, the DSM introduced a dissociative subtype of PTSD into their most recent update; DSM-5.ObjectivesThe current study aimed to examine symptom-level associations between PTSD and dissociation using network analysis among UK Armed Forces veterans resident in Northern Ireland (NI) to identify if there are certain symptoms that may act as bridges between the two constructs.MethodsA large scale cross sectional survey was conducted examining the physical and mental wellbeing of UK Armed Forces Veterans living in NI. The total eligible sample size was 619 (89.8% male), with a mean age of 55.38 years (SD = 10.41). Two networks were estimated, (1) a network consisting of 20 DSM-5 PTSD items and (2) a network consisting of 20 PTSD items and four dissociative items. Expected influence bridge centrality was calculated to examine symptoms with the most/strongest cross-domain associations (i.e. between PTSD and dissociation). The presence of meaningful clustering among symptoms was also explored.Results The PTSD symptoms ‘concentration problems’, ‘flashbacks’ and ‘negative emotional state’ had the highest relative bridge expected influence centrality. Of the four dissociative items, ‘gaps in awareness’ had the highest relative bridge expected influence centrality, followed by ‘cognitive-behavioural re-experiencing’. A community structure of five clusters was detected. Four clusters reflected each subscale of the PCL-5 PTSD items and the final cluster reflected the dissociation items.ConclusionsThis study extends our understanding of PTSD and disociation comorbidity by investigating symptom level relationships; potentially informing future treatments and interventions.DisclosureNo significant relationships.

Contrasting Associations Between Heart Rate Variability and Brainstem-Limbic Connectivity in Posttraumatic Stress Disorder and Its Dissociative Subtype: A Pilot Study.

BackgroundIncreasing evidence points toward the need to extend the neurobiological conceptualization of posttraumatic stress disorder (PTSD) to include evolutionarily conserved neurocircuitries centered on the brainstem and the midbrain. The reticular activating system (RAS) helps to shape the arousal state of the brain, acting as a bridge between brain and body. To modulate arousal, the RAS is closely tied to the autonomic nervous system (ANS). Individuals with PTSD often reveal altered arousal patterns, ranging from hyper- to blunted arousal states, as well as altered functional connectivity profiles of key arousal-related brain structures that receive direct projections from the RAS. Accordingly, the present study aims to explore resting state functional connectivity of the RAS and its interaction with the ANS in participants with PTSD and its dissociative subtype.MethodsIndividuals with PTSD (n = 57), its dissociative subtype (PTSD + DS, n = 32) and healthy controls (n = 40) underwent a 6-min resting functional magnetic resonance imaging and pulse data recording. Resting state functional connectivity (rsFC) of a central node of the RAS – the pedunculopontine nuclei (PPN) – was investigated along with its relation to ANS functioning as indexed by heart rate variability (HRV). HRV is a prominent marker indexing the flexibility of an organism to react adaptively to environmental needs, with higher HRV representing greater effective adaptation.ResultsBoth PTSD and PTSD + DS demonstrated reduced HRV as compared to controls. HRV measures were then correlated with rsFC of the PPN. Critically, participants with PTSD and participants with PTSD + DS displayed inverse correlations between HRV and rsFC between the PPN and key limbic structures, including the amygdala. Whereas participants with PTSD displayed a positive relationship between HRV and PPN rsFC with the amygdala, participants with PTSD + DS demonstrated a negative relationship between HRV and PPN rsFC with the amygdala.ConclusionThe present exploratory investigation reveals contrasting patterns of arousal-related circuitry among participants with PTSD and PTSD + DS, providing a neurobiological lens to interpret hyper- and more blunted arousal states in PTSD and PTSD + DS, respectively.

Prevalence, clinical features, and psychological characteristics of dissociative subtype of posttraumatic stress disorder in Chinese prisoners

ABSTRACT This study aimed to examine prevalence, clinical symptoms, and psychological characteristics of D-PTSD in a sample of Chinese prisoners with probable PTSD. A total of 1458 male prisoners were recruited from a large prison in Guangdong, China. Participants completed self-administrated questionnaires that assessed PTSD and dissociative symptoms, psychopathology, emotion regulation, emotional expressivity, social pleasure, traumatic events, and social support. According to DSM-5 criteria, participants were classified into four groups: D-PTSD, PTSD only, derealization/depersonalization (DD) only, and neither. The proportions of D-PTSD, PTSD only, DD only and neither were 2.5%, 4.7%, 2.4%, and 92.2%, respectively. PTSD symptoms and emotion regulation difficulties were distinguishing for the four groups: PTSD symptoms declined gradually in the order of D-PTSD, PTSD only, DD only, and neither, while emotion regulation difficulties declined in an order from D-PTSD, DD only, and PTSD only to neither, all ps < .001. D-PTSD and DD only had higher depressive and dissociative symptoms than PTSD only and the neither groups, all ps < .001. D-PTSD also had more borderline personality symptoms, emotion regulation difficulties, and more negative emotional expressivity than PTSD only and DD only, all ps < .05. Logistic regressions indicated that D-PTSD reported lower social support compared to PTSD only (OR = 0.95, p < .01), DD only (OR = 0.96, p < .05) and neither (OR = 0.93, p < .001). D-PTSD is common in probable PTSD in prisoners and is associated with complex clinical presentations as well as emotional processing. Social support is an important protective factor of D-PTSD.

A latent profile analysis of the dissociative subtype of PTSD in a sample of UK Armed Forces veterans residing in Northern Ireland

Background: Posttraumatic stress disorder (PTSD) and dissociation have long been associated with each other. In recent years, studies have examined support for the dissociative subtype of PTSD in several different populations. To date, no study has examined whether this subtype exists in UK Armed Forces military veterans residing in Northern Ireland. Northern Ireland has a history of prolonged civil conflict, differentiating the veterans who live in the region from veterans who live in the remainder of the United Kingdom; and increasing the likelihood that they will experience mental health difficulties. Methods: Data was collected through a cross-sectional, self-report survey from military veterans living in Northern Ireland. The effective sample for the current study was 834 veterans (90.38% males, mean age 55.81 years). A latent profile analysis of PTSD and dissociative indicators was conducted to examine the existence of the dissociative PTSD subtype. Results: Four quantitatively different latent profiles were identified; Non-symptomatic, Low PTSD, Moderate PTSD and High PTSD. There was no evidence of a dissociative PTSD subtype. Several military-type variables differentially predicted membership in the latent profiles, including combat exposure, length of service, physical injuries during service and having been medically discharged. Conclusions: The results do not support the Subtype model of the relationship between PTSD and dissociation. However, they have important implications for clinicians working with veterans in the region, as it appears that dissociation is an integral part of the PTSD presentation in Northern Irish veterans.

The Role of the Insula in Classical and Dissociative PTSD: A Double Case Study

ABSTRACT Two service members were diagnosed with PTSD due to military trauma exposure. One presented with the classical manifestation; the other presented with the dissociative subtype. A statistical map revealed anterior localization of insula connectivity in the classical PTSD patient and posterior localization in the dissociative PTSD patient. These differences suggest that dissociative PTSD may be identified, understood, and treated as a disorder related to increased posterior insula connectivity. This double case study provides preliminary evidence for a concrete neuroanatomical discrepancy between insula function in classical and dissociative PTSD that may help explain the emergence of different coping strategies.

The dissociative subtype of PTSD in trauma-exposed individuals: a latent class analysis and examination of clinical covariates

ABSTRACT Background A dissociative subtype of posttraumatic stress disorder (D-PTSD) was introduced into the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) but latent profiles and clinical correlates of D-PTSD remain controversial. Objective The aims of our study were to identify subgroups of individuals with distinct patterns of PTSD symptoms, including dissociative symptoms, by means of latent class analyses (LCA), to compare these results with the categorization of D-PTSD vs. PTSD without dissociative features according to the CAPS-5 interview, and to explore whether D-PTSD is associated with higher PTSD severity, difficulties in emotion regulation, and depressive symptoms. Method A German sample of treatment-seeking individuals was investigated (N = 352). We conducted an LCA on the basis of symptoms of PTSD and dissociation as assessed by the CAPS-5. Moreover, severity of PTSD (PCL-5), difficulties in emotion regulation (DERS), and depressive symptoms (BDI-II) were compared between patients with D-PTSD according to the CAPS-5 interview and patients without dissociative symptoms. Results LCA results suggested a 5-class model with one subgroup showing the highest probability to fulfill criteria for the dissociative subtype and high scores on both BDI and DERS. Significantly higher scores on the DERS, BDI and PCL-5 were found in the D-PTSD group diagnosed with the CAPS-5 (n = 75; 35.7%). Sexual trauma was also reported more often by this subgroup. When comparing the dissociative subtype to the LCA results, only a partial overlap could be found. Conclusions Our findings suggest that patients with D-PTSD have significantly more problems with emotion regulation, more depressive symptoms, and more severe PTSD-symptoms. Given the results of our LCA, we conclude that the dissociative subtype seems to be more complex than D-PTSD as diagnosed by means of the CAPS-5.

Exploring strategies to cope with dissociation and its determinants through functional analysis in patients suffering from PTSD: A qualitative study

IntroductionDissociation is a contraindication for cognitive behavior therapy (CBT) for PTSD and has been observed to impair CBT efficacy. Therefore, there is a need to identify the determinants of dissociation through functional analysis, as well as strategies to cope with dissociation. Identifying such determinants would allow clinicians to treat dissociation and would therefore increase CBT efficacy for patients suffering from dissociation and PTSD. MethodWe recruited 15 patients suffering from dissociative subtype of PTSD. We used self-report scales to measure post-traumatic symptoms, dissociative symptoms and emotion regulation abilities. We used a visual analog scale to measure the ability to control dissociation. A trained clinician then carried out semi-structured interviews to explore the determinants of dissociation. ResultsWe identified different manifestations, positive and negative beliefs, and triggers of dissociation, and strategies to block it. A functional analysis of dissociation was developed based on these data. ConclusionCognitive restructuring techniques could be used to change beliefs about dissociation. Different strategies to block dissociation has been identified in this study, such as concentration, emotion regulation, and reality anchor techniques.

Structure of ICD-11 complex PTSD and relationship with psychoform and somatoform dissociation

ObjectiveThe structure of the relationship between ICD-11 Complex Post-traumatic Stress Disorder (C-PTSD) and dissociative symptoms requires more extensive research, especially with respect to the empirical support for a DSM-5 dissociative subtype of PTSD. The present study sought to examine 1) the structural validity of ICD-11 C-PTSD, 2) the association between latent C-PTSD factors and features of dissociation, and 3) whether patients with C-PTSD show elevated levels of dissociation when compared to PTSD and no ICD-11 PTSD disorder. MethodsA sample of traumatized psychiatric outpatients (N = 114) were diagnosed with a structured interview and subsequently administered the International Trauma Questionnaire (ITQ), the Dissociative Symptom Scale (DSS), and the Somatoform Dissociation Questionnaire, 5-items (SDQ). We used Confirmatory Factor Analysis (CFA) to replicate the established structure of C-PTSD as operationalized with the ITQ. Subsequently, a structural equation model (SEM) approach was employed to examine associations of ITQ with psychoform and somatoform dissociation as measured with the DSS and SDQ. ResultsThe expected factorial structure of C-PTSD was replicated in the present sample, and the domains PTSD and disturbances in self-organization were found to be related but distinct constructs. All ICD-11 C-PTSD latent factors were associated with dissociative experiences. The strongest effects were found for the symptom clusters Affective Dysregulation, Disturbances in Relationship, and Re-Experiencing. However, dissociative Gaps in Awareness and Memory and Sensory Misperception were not predicted by any ICD-11 C-PTSD latent factors. Cumulative levels of dissociative experiences appeared to differentiate ICD-11 PTSD and C-PTSD with significantly higher levels for C-PTSD. ConclusionICD-11 C-PTSD is strongly associated with dissociative phenomena in complex ways. Somatoform and psychoform manifestations of dissociation should be routinely assessed in patients with ICD-11 C-PTSD because such expressions may cover intense affects and painful relationship experiences. Future studies are needed to substantiate the causal and predictive relationship between ICD-11 C-PTSD and dissociation.

Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD.

Individuals with posttraumatic stress disorder (PTSD) are at increased risk for the development of various forms of dementia. Nevertheless, the neuropathological link between PTSD and neurodegeneration remains unclear. Degeneration of the human basal forebrain constitutes a pathological hallmark of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. In this seed‐based resting‐state (rs‐)fMRI study identifying as outcome measure the temporal BOLD signal fluctuation magnitude, a seed‐to‐voxel analyses assessed temporal correlations between the average BOLD signal within a bilateral whole basal forebrain region‐of‐interest and each whole‐brain voxel among individuals with PTSD (n = 65), its dissociative subtype (PTSD+DS) (n = 38) and healthy controls (n = 46). We found that compared both with the PTSD and healthy controls groups, the PTSD+DS group exhibited increased BOLD signal variability within two nuclei of the seed region, specifically in its extended amygdaloid region: the nucleus accumbens and the sublenticular extended amygdala. This finding is provocative, because it mimics staging models of neurodegenerative diseases reporting allocation of neuropathology in early disease stages circumscribed to the basal forebrain. Here, underlying candidate etiopathogenetic mechanisms are neurovascular uncoupling, decreased connectivity in local‐ and large‐scale neural networks, or disrupted mesolimbic dopaminergic circuitry, acting indirectly upon the basal forebrain cholinergic pathways. These abnormalities may underpin reward‐related deficits representing a putative link between persistent traumatic memory in PTSD and anterograde memory deficits in neurodegeneration. Observed alterations of the basal forebrain in the dissociative subtype of PTSD point towards the urgent need for further exploration of this region as a potential candidate vulnerability mechanism for neurodegeneration in PTSD.

Examining Neuroendocrine and Inflammatory Biomarker Profiles to Characterize PTSD Subtypes and Symptom Profiles

Posttraumatic Stress Disorder (PTSD) is characterized by various symptom profiles and high comorbidities with other conditions, including Major Depressive Disorder (MDD). A dissociative subtype of PTSD (PTSD-DST) has been specified by additional symptoms of depersonalization and derealisation. However, the underlying neurobiology of PTSD-DST is poorly understood. This study examined neuroendocrine and inflammatory biomarkers in relation to symptom profiles of PTSD.

The impact of childhood trauma on the emergence and development of dissociative disorders

Dissociative experiences are common both in children and adults. Their frequency and severity range from normal dissociation to pathological fragmentation of identity. High rates of dissociation and Dissociative Disorders have been documented in both community and clinical samples. Trauma, especially chronic trauma, plays an essential role in the development and long-term presence of dissociative symptoms. During overwhelming and often traumatic experiences dissociation protects the individual by psychological detachment from the unbearable reality. Chronic dissociative experiences might cause severe disintegration of the individual’s mental experience. The Trauma Model suggests that dissociation is a psychobiological response which enables survival during and after the traumatic event. The Developmental Model is based on an assumption that disturbed attachment, especially early interpersonal trauma, might lead to the development of severe dissociation in children and adolescents, often lasting into adulthood. Diagnostic systems include three diagnoses that deal with the specific relationship between trauma and dissociation. Two of these diagnoses have been recognized recently - Complex PTSD (ICD-11) and the Dissociative Subtype of PTSD (DSM-5); one has already been established - the Dissociative Identity Disorder. Patients with Dissociative Disorders suffer from a range of symptoms. The most severe symptoms include chronic suicidal ideation and frequent suicide attempts. Therefore, researchers and clinicians should routinely assess dissociation in their everyday practice. In patients with Dissociative Disorders, the main treatment goal is the integration of their mental experience.

How Processing of Sensory Information From the Internal and External Worlds Shape the Perception and Engagement With the World in the Aftermath of Trauma: Implications for PTSD.

Post-traumatic stress disorder (PTSD) is triggered by an individual experiencing or witnessing a traumatic event, often precipitating persistent flashbacks and severe anxiety that are associated with a fearful and hypervigilant presentation. Approximately 14–30% of traumatized individuals present with the dissociative subtype of PTSD, which is often associated with repeated or childhood trauma. This presentation includes symptoms of depersonalization and derealization, where individuals may feel as if the world or self is “dream-like” and not real and/or describe “out-of-body” experiences. Here, we review putative neural alterations that may underlie how sensations are experienced among traumatized individuals with PTSD and its dissociative subtype, including those from the outside world (e.g., touch, auditory, and visual sensations) and the internal world of the body (e.g., visceral sensations, physical sensations associated with feeling states). We postulate that alterations in the neural pathways important for the processing of sensations originating in the outer and inner worlds may have cascading effects on the performance of higher-order cognitive functions, including emotion regulation, social cognition, and goal-oriented action, thereby shaping the perception of and engagement with the world. Finally, we introduce a theoretical neurobiological framework to account for altered sensory processing among traumatized individuals with and without the dissociative subtype of PTSD.

Efficacy and safety results from the first pivotal phase 3 randomized controlled trial of mdma-assisted psychotherapy for treatment of severe chronic PTSD

IntroductionPosttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Previous research has led to the designation of 3,4-methylenedioxymethamphetamine (MDMA) as a Breakthrough Therapy for treatment of post-traumatic stress disorder (PTSD) when administered as an adjunct to psychotherapy.ObjectivesHere we report the findings of the first randomized, double-blind, Phase 3 trial assessing the efficacy and safety of 3 sessions with a flexible dose of MDMA or placebo administered under direct observation to participants with severe PTSD (n = 100) as an adjunct to inner-directed psychotherapy.MethodsChange in PTSD symptoms (CAPS-5) and functional impairment (SDS) were assessed by a central, blinded Independent Rater Pool at baseline and following each treatment session. Adverse events (AEs), concomitant medications, suicidal ideation and behavior were tracked throughout the study. Vital signs were measured during experimental sessions. The primary endpoint was 18 weeks post-randomization.ResultsChange in CAPS-5 and SDS, placebo-subtracted Cohen’s d effect size, and a responder analysis will be presented. There were three serious AEs of suicidal ideation or behavior reported. MDMA was well tolerated, with some treatment emergent AEs occurring at greater frequency for the MDMA group during and after experimental sessions.ConclusionsIf MDMA-assisted psychotherapy significantly attenuates PTSD symptomatology and associated functional impairment, these results will form the basis for marketing authorization applications worldwide, including among participants with dissociative subtype of PTSD, depression, history of alcohol and substance use disorders, and adverse childhood experiences.DisclosureNo significant relationships.

Dissociative symptoms predict severe illness presentation in Canadian public safety personnel with presumptive post-traumatic stress disorder (PTSD)

ABSTRACT Background: Post-traumatic stress disorder affects 9% of individuals across their lifetime and increases nearly fourfold to 35% in Canadian public safety personnel (PSP). On-the-job experiences of PSP frequently meet criteria for traumatic events, making these individuals highly vulnerable to exposures of trauma and the negative consequences of PTSD. Few studies have reported on the clinical characteristics of Canadian samples of PSP and even fewer have examined the dissociative subtype of PTSD, which is associated with more severe, chronic traumatic experiences, and worse outcomes. Objective: This study aimed to characterize dissociative symptoms, PTSD symptom severity, and other clinical variables among Canadian PSP with presumptive PTSD. Methods: We sampled current and past PSP in Canada from both inpatient and outpatient populations (N = 50) that were enrolled in a psychological intervention. Only baseline testing data (prior to any intervention) were analysed in this study, such as PTSD symptom severity, dissociative symptoms, emotion dysregulation, and functional impairment. Results: In our sample, 24.4% self-reported elevated levels of dissociation, specifically symptoms of depersonalization and derealization. Depersonalization and derealization symptoms were associated with more severe PTSD symptoms, greater emotion dysregulation, and functional impairment. Conclusions: Nearly a quarter of this sample of Canadian PSP reported experiencing elevated levels of PTSD-related dissociation (depersonalization and derealization). These high levels of depersonalization and derealization were consistently positively associated with greater illness severity across clinical measures. It is imperative that dissociative symptoms be better recognized in patient populations that are exposed to chronic traumatic events such as PSP, so that treatment interventions can be designed to target a more severe illness presentation.

A reciprocal inhibition model of alternations between under-/overemotional modulatory states in patients with PTSD

Patients with posttraumatic stress disorder (PTSD) appear to manifest two opposing tendencies in their attentional biases and symptoms. However, whether common neural mechanisms account for their opposing attentional biases and symptoms remains unknown. We here propose a model in which reciprocal inhibition between the amygdala and ventromedial prefrontal cortex (vmPFC) predicts synchronized alternations between emotional under- and overmodulatory states at the neural, behavioral, and symptom levels within the same patients. This reciprocal inhibition model predicts that when the amygdala is dominant, patients enter an emotional undermodulatory state where they show attentional bias toward threat and manifest re-experiencing symptoms. In contrast, when the vmPFC is dominant, patients are predicted to enter an emotional overmodulatory state where they show attentional bias away from threat and avoidance symptoms. To test the model, we performed a behavioral meta-analysis (total N = 491), analyses of own behavioral study (N = 20), and a neuroimaging meta-analysis (total N = 316). Supporting the model, we found the distributions of behavioral attentional measurements to be bimodal, suggesting alternations between the states within patients. Moreover, attentional bias toward threat was related to re-experiencing symptoms, whereas attentional bias away from threat was related with avoidance symptoms. We also found that the increase and decrease of activity in the left amygdala activity was related with re-experiencing and avoidance symptoms, respectively. Our model may help elucidate the neural mechanisms differentiating nondissociative and dissociative subtypes of PTSD, which usually show differential emotional modulatory levels. It may thus provide a new venue for therapies targeting each subtype.