White matter abnormalities in first-episode patients with depersonalization/derealization disorder: A tract-based spatial statistics study.

BACKGROUND: Neuroimaging studies on depersonalization / derealization disorder (DPD) have revealed that there are structural and functional alterations across numerous brain regions. However, to date, the exact white matter abnormalities that are associated with different clinical symptoms and cognitive impairments in first-episode, drug-naïve patients with DPD remain unclear. METHODS: Overall, 25 first-episode, drug-naïve patients with DPD and 23 healthy controls were recruited and underwent DTI scans. The tract-based spatial statistics analysis was conducted in order to determine white matter microstructural changes between the two groups. Correlation analysis was conducted between the fractional anisotropy (FA) of abnormal WM fibers and the total score of the 30-item Cambridge Depersonalization Scale (CDS-30), cognitive assessments. RESULTS: Patients with DPD demonstrated higher FA in the right corpus callosum (CC), and posterior corona radiate (CR), compared to healthy controls. The FA in the right CC demonstrated a positive correlation with total score of CDS-30, numbing, unreality of self, perceptual alterations, and temporal disintegration, respectively. FA in the right CR region indicated a positive correlation with the total score of CDS-30, unreality of self, perceptual alterations, and temporal disintegration, respectively. Furthermore, FA in the right CR region was found to be negatively correlated with the Continuous Performance Test and the Stroop color-word test. CONCLUSION: The altered white matter microstructure and cognitive impairments of medication naïve DPD patients were observed. Abnormalities in the integrity of CC and CR were associated with severity of symptoms and cognitive impairments, which may provide a potential biomarker for clinical studies on DPD.

PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting-state functional connectivity and its predictive validity using machine learning.

Individuals with post-traumatic stress disorder (PTSD) typically experience states of reliving and hypervigilance; however, the dissociative subtype of PTSD (PTSD+DS) presents with additional symptoms of depersonalization and derealization. Although the insula is critical to emotion processing, its association with these contrasting symptom profiles is yet to be fully delineated. Accordingly, we investigated insula subregion resting-state functional connectivity patterns among individuals with PTSD, PTSD+DS, and healthy controls. Using SPM12 and PRONTO software, we implemented a seed-based resting-state functional connectivity approach, along with multiclass Gaussian process classification machine learning, respectively, in order to evaluate unique patterns and the predictive validity of insula subregion connectivity among individuals with PTSD (n = 84), PTSD+DS (n = 49), and age-matched healthy controls (n = 51). As compared to PTSD and PTSD+DS, healthy controls showed increased right anterior and posterior insula connectivity with frontal lobe structures. By contrast, PTSD showed increased bilateral posterior insula connectivity with subcortical structures, including the periaqueductal gray. Strikingly, as compared to PTSD and controls, PTSD+DS showed increased bilateral anterior and posterior insula connectivity with posterior cortices, including the left lingual gyrus and the left precuneus. Moreover, machine learning analyses were able to classify PTSD, PTSD+DS, and controls using insula subregion connectivity patterns with 80.4% balanced accuracy (p < .01). These findings suggest a neurobiological distinction between PTSD and its dissociative subtype with regard to insula subregion functional connectivity patterns. Furthermore, machine learning algorithms were able to utilize insula resting-state connectivity patterns to discriminate between participant groups with high predictive accuracy.

Depersonalization- and derealization-like phenomena of epileptic origin.

OBJECTIVE: Depersonalization refers to the sensation of being detached from one's body, often associated with feelings of loss of control over one's own body, actions, or thoughts. Derealization refers to the altered perception of one's surroundings that is experienced as unreal. Although usually reported by psychiatric patients suffering from depression or anxiety, single case reports and small case series have described depersonalization- and derealization-like symptoms in the context of epilepsy. METHODS: We investigated the brain mechanisms of ictal depersonalization- and derealization like symptoms by analyzing clinical and neuropsychological data as well as the epileptogenic zone based on a multimodal approach in a group of patients reporting depersonalization- (n = 9) and derealization-like symptoms (n = 7), from a single presurgical epilepsy center with focal epilepsy. We compared them with a group of control patients with experiential phenomena due to temporal lobe epilepsy (n = 28). RESULTS: We show that all patients with ictal depersonalization-like symptoms report altered self-identification with their body and mostly suffer from frontal lobe epilepsy with the epileptogenic zone in the dorsal premotor cortex, while patients with derealization-like symptoms suffer from temporal lobe epilepsy. This finding is supported by post-ictal neuropsychological deficits, showing that depersonalization-like symptoms were significantly more often associated with frontal lobe dysfunction as compared to the control patients and patients with derealization-like symptoms. CONCLUSION: We argue that depersonalization of epileptic origin constitutes a distinct disorder due to frontal lobe epilepsy. We discuss these findings with respect to earlier accounts of depersonalization and the recent concept of bodily self-consciousness.

White matter network alterations in patients with depersonalization/derealization disorder.

BACKGROUND: Depersonalization/derealization disorder (DPD) is a chronic and distressing condition characterized by detachment from oneself and/or the external world. Neuroimaging studies have associated DPD with structural and functional alterations in a variety of distinct brain regions. Such local neuronal changes might be mediated by altered interregional white matter connections. However, to our knowledge, no research on network characteristics in this patient population exists to date. METHODS: We explored the structural connectome in 23 individuals with DPD and 23 matched, healthy controls by applying graph theory to diffusion tensor imaging data. Mean interregional fractional anisotropy (FA) was used to define the network weights. Group differences were assessed using network-based statistics and a link-based controlling procedure. RESULTS: Our main finding refers to lower FA values within left temporal and right temporoparietal regions in individuals with DPD than in healthy controls when using a link-based controlling procedure. These links were also associated with dissociative symptom severity and could not be explained by anxiety or depression scores. Using network-based statistics, no significant results emerged. However, we found a trend for 1 subnetwork that may support the model of frontolimbic dysbalance suggested to underlie DPD symptomatology. LIMITATIONS: To ensure ecological validity, patients with certain comorbidities or psychotropic medication were included in the study. Confirmatory replications are necessary to corroborate the results of this explorative investigation. CONCLUSION: In patients with DPD, the structural connectivity between brain regions crucial for multimodal integration and emotion regulation may be altered. Aberrations in fibre tract communication seem to be not solely a secondary effect of local grey matter volume loss, but may present a primary pathophysiology in patients with DPD.

Resting-State Networks of Adolescents Experiencing Depersonalization-Like Illusions: Cross-sectional and Longitudinal Findings.

The mirror-gazing task (MGT) experimentally induces illusions, ranging from simple color changes in the specular image of oneself, to depersonalization-like anomalous self-experiences (ASE) as in experiencing one's specular image as someone else. The objective was to characterize how connectivity in resting-state networks (RSNs) differed in adolescents reporting such depersonalization-like ASEs during the MGT, in a cross-sectional (Y1) and in a longitudinal manner (a year after). 75 adolescents were recruited; for the cross-sectional analysis, participants were split into 2 groups: those who reported depersonalization-like ASEs on the MGT (ASE), and those who did not (NoASE). For the longitudinal analysis, participants were split into 3 groups whether they experienced MGT depersonalization-like ASEs: only at Y1 (Remitters), both times (Persisters), or never (Controls). Participants also filled out self-reports assessing schizotypal personality (Schizotypal Personality Questionnaire [SPQ]), and underwent resting-state functional MRI procedure (rs-fMRI). A group level Independent Component Analysis (ICA) was conducted and voxel-wise inter-group differences within RSNs were examined. The rs-fMRI analysis revealed lower connectivity of specific visual areas within the primary visual network (PVN), and higher connectivity of regions within the Default Mode Network (DMN) when contrasting the ASE and NoASE groups. The areas that were atypically connected within the PVN further presented differential pattern of connectivity in the longitudinal analysis. Atypical connectivity of visual area within the DMN at Y1 was associated with higher scores on the disorganized dimension of schizotypy at the second evaluation. The present study uncovers a subtle signature in the RSNs of non-clinical adolescents who experienced task-induced ASEs.

Dissociation and Alterations in Brain Function and Structure: Implications for Borderline Personality Disorder.

Dissociation involves disruptions of usually integrated functions of consciousness, perception, memory, identity, and affect (e.g., depersonalization, derealization, numbing, amnesia, and analgesia). While the precise neurobiological underpinnings of dissociation remain elusive, neuroimaging studies in disorders, characterized by high dissociation (e.g., depersonalization/derealization disorder (DDD), dissociative identity disorder (DID), dissociative subtype of posttraumatic stress disorder (D-PTSD)), have provided valuable insight into brain alterations possibly underlying dissociation. Neuroimaging studies in borderline personality disorder (BPD), investigating links between altered brain function/structure and dissociation, are still relatively rare. In this article, we provide an overview of neurobiological models of dissociation, primarily based on research in DDD, DID, and D-PTSD. Based on this background, we review recent neuroimaging studies on associations between dissociation and altered brain function and structure in BPD. These studies are discussed in the context of earlier findings regarding methodological differences and limitations and concerning possible implications for future research and the clinical setting.

Deliberate and spontaneous sensations of disembodiment: capacity or flaw?

INTRODUCTION: Hallucinations that involve shifts in the subjectively experienced location of the self, have been termed "out-of-body experiences" (OBEs). Early psychiatric accounts cast OBEs as a specific instance of depersonalisation and derealisation disorder (DPD-DR). However, during feelings of alienation and lack of body realism in DPD-DR the self is experienced within the physical body. Deliberate forms of "disembodiment" enable humans to imagine another's visuo-spatial perspective taking (VPT), thus, if a strong relationship between deliberate and spontaneous forms of disembodiment could be revealed, then uncontrolled OBEs could be "the other side of the coin" of a uniquely human capacity. METHODS: We present a narrative review of behavioural and neuroimaging work emphasising methodological and theoretical aspects of OBE and VPT research and a potential relationship. RESULTS: Results regarding a direct behavioural relationship between VPT and OBE are mixed and we discuss reasons by pointing out the importance of using realistic tasks and recruiting genuine OBEers instead of general DPD-DR patients. Furthermore, we review neuroimaging evidence showing overlapping neural substrates between VPT and OBE, providing a strong argument for a relationship between the two processes. CONCLUSIONS: We conclude that OBE should be regarded as a necessary implication of VPT ability in humans, or even as a necessary and potentially sufficient condition for the evolution of VPT.

Feeling unreal: a PET study of depersonalization disorder.

OBJECTIVE: The goal of this study was to assess brain glucose metabolism and its relationship to dissociation measures and clinical symptoms in DSM-IV depersonalization disorder. METHOD: Positron emission tomography scans coregistered with magnetic resonance images of eight subjects with depersonalization disorder were compared to those of 24 healthy comparison subjects. The two groups did not differ in age, sex, education, performance on a baseline neuropsychological battery, or performance on a verbal learning task administered during [(18)F]fluorodeoxyglucose uptake. A cortical analysis by individual Brodmann's areas was performed. RESULTS: Compared to the healthy subjects, subjects with depersonalization disorder showed significantly lower metabolic activity in right Brodmann's areas 22 and 21 of the superior and middle temporal gyri and had significantly higher metabolism in parietal Brodmann's areas 7B and 39 and left occipital Brodmann's area 19. Dissociation and depersonalization scores among the subjects with depersonalization disorder were significantly positively correlated with metabolic activity in area 7B. CONCLUSIONS: Depersonalization appears to be associated with functional abnormalities along sequential hierarchical areas, secondary and cross-modal, of the sensory cortex (visual, auditory, and somatosensory), as well as areas responsible for an integrated body schema. These findings are in good agreement with the phenomenological conceptualization of depersonalization as a dissociation of perceptions as well as with the subjective symptoms of depersonalization disorder.