Symptoms of depersonalisation/derealisation disorder as measured by brain electrical activity: A systematic review

Highlights

• EEG offers potential electrophysiological biomarkers to study core DPD symptoms.

• EEG power spectrum, ERPs, HEPs and vestibular evoked potentials are reviewed.

• Further studies are urgently needed for fully developing their diagnostic potential.

• Comprehensive testing of multiple electrophysiological signals is recommended.

Abstract

Depersonalisation/derealisation disorder (DPD) refers to frequent and persistent detachment from bodily self and disengagement from the outside world. As a dissociative disorder, DPD affects 1–2 % of the population, but takes 7–12 years on average to be accurately diagnosed. In this systematic review, we comprehensively describe research targeting the neural correlates of core DPD symptoms, covering publications between 1992 and 2020 that have used electrophysiological techniques. The aim was to investigate the diagnostic potential of these relatively inexpensive and convenient neuroimaging tools. We review the EEG power spectrum, components of the event-related potential (ERP), as well as vestibular and heartbeat evoked potentials as likely electrophysiological biomarkers to study DPD symptoms. We argue that acute anxiety- or trauma-related impairments in the integration of interoceptive and exteroceptive signals play a key role in the formation of DPD symptoms, and that future research needs analysis methods that can take this integration into account. We suggest tools for prospective studies of electrophysiological DPD biomarkers, which are urgently needed to fully develop their diagnostic potential.

Introduction

Depersonalisation/derealisation refers to a state of mind in which a person feels detached and disconnected from their bodies and own senses as well as from their surroundings (Phillips and Sierra, 2003). This condition can be accompanied by a sense of unreality about the outside world and by out-of-body experiences, and is believed to be a defensive mechanism of the brain in order to protect the organism in acute anxiety or traumatic situations (Hunter et al., 2003; Shilony and Grossman, 1993; Sierra and Berrios, 1998; Stein and Simeon, 2009). For instance, temporary occurrences of depersonalisation have been reported by almost 50 % of college students (Dixon, 1963). Fatigue (Tibubos et al., 2018), sleep deprivation (van Heugten-van der Kloet et al., 2015), or travelling to unfamiliar places can also be the cause of transient depersonalisation/derealisation (Kaplan et al., 1998). However, in cases where the symptoms are chronic, it is considered a type of dissociative disorder (depersonalisation/derealisation disorder (DPD); Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (American Psychiatric Association, 2013)).

Although the exact cause of DPD is not yet known, traumatic experiences and childhood anxiety are thought to be common triggers (Lee et al., 2012; Simeon et al., 2001b). It can also be provoked by intense stress, depression, panic attacks, and ingestion of psychoactive substances (Mathew et al., 1999; Medford et al., 2003; Simeon, 2004). Patients experience persistent and frequent feelings of disembodiment or detachment from their physical self as well as emotional numbness that may extend beyond the present moment to include memories and imagination. Since derealisation is an inseparable aspect of DPD in most cases, the symptoms may also include detachment from surroundings, as if the world around the patient is unreal, or a weakened ability to respond to emotional circumstances, although the capacity for emotional expression and reality testing remain intact (Hollander et al., 1992; Sierra and David, 2011). DPD can be accompanied by anxiety, depression or schizophrenia (Stein et al., 1997), as well as difficulties in concentration and memory retrieval (Lambert et al., 2001a), which can profoundly affect the quality of life for patients and interfere with their daily activities and social relationships. Identifying DPD, as well as its risks and neuroprotective factors, at early stages should thus be a critical endeavour for clinical practice and research.

DPD has a prevalence of about 1–2 % of the population (Hunter et al., 2004; Lee et al., 2012; Michal et al., 2007), which is comparable to that of schizophrenia and obsessive-compulsive disorder, with an equal gender ratio and an average onset age in early adulthood (Baker et al., 2003; Michal et al., 2016; Simeon, 2004; Simeon et al., 2003). Nevertheless, DPD is one of the most prevalent but under-diagnosed psychiatric disorders (Hunter et al., 2017; Michal et al., 2010). Generally, there are no medical laboratory tests for diagnosis of dissociative disorders, and since patients find it difficult to describe the symptoms of depersonalisation and derealisation, it currently takes an average of 7–12 years to correctly diagnose DPD (Hunter et al., 2017). Diagnosis is hampered by a lack of awareness of DPD among medical practitioners (Medford et al., 2005) and its symptomatology overlap with medical conditions such as epilepsy and migraine (Devinsky et al., 1989; Lambert et al., 2002) and psychiatric conditions such as depression and post-traumatic stress disorder (Armour et al., 2014). Therefore, delineating the neurophysiological correlates of DPD may be of great importance for an early diagnosis of DPD as discriminate from its transient form and from other conditions.

In this review, we provide an overview of the structural and functional neurophysiology in DPD, with a particular focus on studies aiming to characterise the cardinal symptoms of the disorder such as feelings of disembodiment and emotional numbing by measuring the electrical activity of the brain. Electrophysiological neuroimaging techniques are of great interest because of their ease of application and cost-effectiveness for clinical practice. Therefore, we intend to identify and introduce electrophysiological biomarkers associated with DPD symptoms, which may have the potential to help with early recognition of this under-diagnosed psychiatric condition. Our paper demonstrates both the urgent need to replicate promising findings on a larger scale and the potential for further electrophysiological pattern analysis to characterise DPD.

Several methods have been used to measure the functional characteristics of DPD symptoms within the autonomic nervous system (galvanic skin response, heart rate) and the central nervous system (EEG, ERPs, HEPs, fMRI, PET). The Galvanic Skin Response (GSR) tracks changes in the conductivity of human skin due to sweating, reflective of the arousal related to the intensity of emotional states. This property has made GSR a useful approach to investigate emotional dysregulations in DPD. Studies using the GSR have elucidated differential autonomic nervous system responses to salient stimuli in DPD, and the impairment is mostly in responding to unpleasant and threatening emotional stimuli rather than pleasant ones (Michal et al., 2013; Monde et al., 2013; Sierra et al., 2006). For instance, research by Dewe et al. (2016) observed suppressed GSRs during the reception of body-threat-like stimuli (blood donation) in DPD patients. Giesbrecht et al. (2010) recorded a different temporal pattern of GSRs in DPD patients compared to healthy individuals while watching an anxiety-inducing movie scene. The response of the patients was characterized by an early peak and a flattened pattern afterwards (even after clip offset), while the control group exhibited a more gradual incremental pattern during the clip followed by a decreasing pattern after clip offset. Peak latency was inversely associated with the severity of DPD symptoms, and patients also showed higher baseline skin responses compared to the control group. Jay et al. (2014) measured DPD patients’ galvanic skin responses and used repetitive transcranial magnetic stimulation (rTMS) to confirm the causal role of ventrolateral prefrontal cortex in these atypical patterns of physiological arousal.

Several neuroimaging studies in the literature have targeted central neural patterns and possible abnormal activities in DPD with functional magnetic resonance imaging (fMRI) (Phillips and Sierra, 2003; Röder et al., 2007), positron emission tomography (PET) (Simeon et al., 2000), and electroencephalography (EEG). These studies predominantly compare the neural substrates of DPD patients with control subjects and have mainly focused on two core aspects of DPD, emotional numbing and disembodiment (Simeon et al., 2008). For instance, various fMRI studies (Lemche et al., 2007, 2008; Mancini-Marïe et al., 2006) have investigated the neural responses of DPD patients to emotional versus neutral stimuli (Medford et al., 2006; Phillips et al., 2001). Results illustrate that emotional numbing (the attenuation of emotional experiences as a result of inhibitory processes) in DPD is associated with reduced activity in brain areas responsible for emotional processing, particularly the insula and limbic regions including hypothalamus and amygdala (Medford et al., 2016). Lemche et al. (2007) showed an inverse relationship between activity in hypothalamus and amygdala and the intensity of positive and negative emotional stimuli in a group of DPD patients compared with controls. fMRI studies also showed increased activation of right ventrolateral prefrontal cortex in DPD patients exhibiting emotional numbness in response to aversive stimuli (Medford et al., 2006; Phillips et al., 2001). Similarly, increased activation of dorsal prefrontal cortex, which plays a role in emotional suppression (Etkin et al., 2006), was found during the processing of both positive and negative emotional facial expressions in DPD patients (Lemche et al., 2007). Dorsal prefrontal activation was inversely related to skin conductance levels. This suggests that prefrontal regions actively suppress the operation of emotional cortical and limbic regions. In line with this proposal, fifteen minutes of 1 Hz inhibitory rTMS to the right ventrolateral prefrontal cortex was found to result in an increase of skin conductance capacity, which reflects the capacity of autonomic responses to emotional stimuli (Jay et al., 2014).

Investigations of disembodiment, another critical (but highly distinctive) characteristic of DPD, can be found less frequently in the DPD literature. Nevertheless, Paul et al. (2019) recently conducted a comprehensive fMRI study on the functional connectivities between brain areas that might be associated with depersonalisation/derealisation symptoms (such as extrastriate body area, hippocampus, medial prefrontal cortex, and posterior and anterior insular cortex) in patients with major depressive disorder. Results revealed that decreased functional connectivity between extrastriate body area (which plays a role in the perception of body parts) and default mode network (which is associated with the processing of self-relevant, autobiographical information) is related to depersonalisation/derealisation symptoms in major depressive disorder. Altered functional connectivity of the default mode network and particular areas in the primary visual network has also been discovered by Derome et al. (2018) in transient depersonalisation.

Among the neuroimaging techniques for the analysis of brain activity, EEG holds great promise as a diagnostic tool because of its non-invasive nature, low costs and simple setup. It provides information about the ongoing neural processes in the cerebral cortex with high temporal resolution. This paper aims to provide a review of studies on DPD using electrophysiological signals to detect and introduce electrophysiological biomarkers associated with DPD symptoms. It also addresses some recent developments in the theories of self-consciousness that can potentially help to explain the unique symptomatology of DPD.